Systematic review of efficacy, safety and pharmacokinetics of intravenous and intraventricular vancomycin for central nervous system infections.

Objective: The decision of vancomycin dosage for central nervous system (CNS) infections is still a challenge because its bactericidal nature in cerebrospinal fluid (CSF) has not been confirmed by human studies. This study systematically reviewed the literatures on vancomycin in patients with meningitis, ventriculitis, and CNS device-associated infections, to assess efficacy, safety, and pharmacokinetics to better serve as a practical reference. Methods: Medline, Embase, and Cochrane Library were searched using terms vancomycin, Glycopeptides, meningitis, and central nervous system infections. Data were extracted including characteristics of participants, causative organism(s), administration, dosage, etc., The clinical response, microbiological response, adverse events and pharmacokinetic parameters were analyzed. Results: Nineteen articles were included. Indications for vancomycin included meningitis, ventriculitis, and intracranial device infections. No serious adverse effects of intravenous (IV) and intraventricular (IVT) vancomycin have been reported. Dosages of IV and IVT vancomycin ranged from 1000-3000 mg/day and 2-20 mg/day. Duration of IV and IVT vancomycin therapy most commonly ranged from 3-27 days and 2-21 days. Therapeutic drug monitoring was conducted in 14 studies. Vancomycin levels in CSF in patients using IV and IVT vancomycin were varied widely from 0.06 to 22.3 mg/L and 2.5-292.9 mg/L. No clear relationships were found between vancomycin CSF levels and efficacy or toxicity. Conclusion: Using vancomycin to treat CNS infections appears effective and safe based on current evidence. However, the optimal regimens are still unclear. Higher quality clinical trials are required to explore the vancomycin disposition within CNS.

Fever of unknown origin (FUO) in children: a single-centre experience from Beijing, China.

OBJECTIVE: To date, there is no standard diagnostic practice to identify the underlying disease-causing mechanism for paediatric patients suffering from chronic fever without any specific diagnosis, which is one of the leading causes of death in paediatric patients. Therefore, we aimed this retrospective study to analyse medical records of paediatric patients with fever of unknown origin (FUO) to provide a preliminary basis for improving the diagnostic categories and facilitate the treatment outcomes. DESIGN: A retrospective study. SETTING: Beijing Children's Hospital. PARTICIPANTS: Clinical data were collected from 1288 children between 1 month and 18 years of age diagnosed with FUO at Beijing Children's Hospital between January 2010 and December 2017. INTERVENTIONS: According to the aetiological composition, age, duration of fever and laboratory examination results, the diagnostic strategies were analysed and formulated. PRIMARY AND SECONDARY OUTCOME MEASURES: The statistical analyses were carried out using SPSS V.24.0 platform along with the χ2 test and analysis of variance (p<0.05). RESULTS: The duration of fever ranged from 2 weeks to 2 years, with an average of 6 weeks. There were 656 cases (50.9%) of infectious diseases, 63 cases (4.9%) of non-infectious inflammatory diseases (NIIDs), 86 cases (6.7%) of neoplastic diseases, 343 cases (26.6%) caused by miscellaneous diseases and 140 cases (10.9%) were undiagnosed. With increasing age, the proportion of FUO from infectious diseases gradually decreased from 73.53% to 44.21%. NIID was more common in children over 3 years old, and neoplastic diseases mainly occurred from 1 to 6 years of age. Among miscellaneous diseases, the age distribution was mainly in school-aged children over 6 years. Respiratory tract infection was the most common cause of FUO in children, followed by bloodstream infections. Bacterial infection was the most common cause in children with less than 1 year old, while the virus was the main pathogen in children over 1 year old. CONCLUSIONS: The diagnosis of neoplastic diseases and miscellaneous diseases-related diseases still depends mainly on invasive examination. According to our clinical experience, the diagnostic process was formulated based on fever duration and the type of disease. This process can provide a guide for the diagnosis and treatment of paediatric FUO in the future.

Tritium diffusion in a Li2TiO3 crystal terminated with the (001) surface from first-principles calculations.

The tritium release behavior of the Li2TiO3 crystal has become an important index to evaluate its comprehensive performance as a solid breeder material in nuclear fusion reactors. The tritium diffusion on the surface (surface diffusion) and diffusion from the inside to the surface (hopping diffusion) in Li2TiO3 crystals with a 1/3-Li(001) surface are systematically investigated by the first-principles method. Possible adsorption sites, diffusion pathways and energy barriers of surface diffusion and hopping diffusion have been calculated and analyzed, respectively. Tritium atoms are found to diffuse preferentially along the [100] direction on the surface and two equivalent pathways across the surface were identified. The obtained activation energies are about 0.50 eV for surface diffusion and 1.56 eV for hopping diffusion. The local density of states and Bader charge for typical surface diffusion and hopping diffusion pathways are calculated and analyzed. The results reveal that the tritium (T) atom bonds with neighboring oxygen (O) atoms during the surface diffusion, while the T-O interaction is significantly weakened in the hopping diffusion which results in the higher activation energy than that of surface diffusion. In combination with our previous work, a complete tritium diffusion model for the Li2TiO3 crystal is proposed and the corresponding tritium diffusion coefficients are obtained. Our obtained activation energies are in the same range as previous experimental data and could provide theoretical support for the future related experiments.

Efficacy and Safety of Mechanical Thrombectomy for Acute Mild Ischemic Stroke with Large Vessel Occlusion.

BACKGROUND The suitability of mechanical thrombectomy (MT) for patients with acute mild ischemic stroke (AMIS) caused by large vessel occlusion (LVO) is controversial. This study evaluated MT in patients with AMIS and LVO. MATERIAL AND METHODS Forty-seven patients diagnosed as AMIS with LVO received MT or intravenous thrombolysis (IVT). Primary outcomes were National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale scores. Secondary outcomes were incidence of systemic complications and symptomatic intracranial hemorrhage. RESULTS There were no significant differences between IVT and MT groups for gender, age, risk factors of cerebrovascular disease, past history, NIHSS score at admission, blood pressure, and LVO sites. For all patients, the NIHSS scores at discharge were lower than those at admission. Patients with excellent outcomes were 66.6% (16/24) in the IVT group and 60.8% (14/23) in the MT group; favorable outcome rates were 75% (18/24) in the IVT group and 69.6% (16/23) in the MT group, with no significant differences between groups. Twelve patients (52.2%) in the MT group and 5 (20.8%) in the IVT group had systemic complications. Symptomatic intracranial hemorrhage was not detected in the IVT group, but manifested in 2 (8.7%) patients in the MT group. During 90-day follow-up, 1 patient died in each of the IVT and MT groups, with 4.2% and 4.4% mortality rates, respectively. CONCLUSIONS The efficacy of MT and IVT was comparable in AMIS patients with LVO. While MT had a higher incidence of systemic complications, its short- and long-term effects were equivalent to IVT.

Population Pharmacokinetics and Dosing Optimization of Azithromycin in Children with Community-Acquired Pneumonia.

Azithromycin is extensively used in children with community-acquired pneumonia (CAP). Currently, the intravenous azithromycin is used off-label in children partly due to lacking of pharmacokinetic data. Our objective was to evaluate the population pharmacokinetics (PPK) and optimize dose strategy in order to improve treatment in this distinctive population. This was a prospective, multicenter, open-labeled pharmacokinetic study. Blood samples were collected from hospitalized pediatric patients and concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). PPK analysis was conducted using NONMEM software. The pharmacokinetic data from 95 pediatric patients (age range, 2.1 to 11.7 years) were available for analysis. The PPK was best fitted by a two-compartment model with linear elimination. Covariate analysis verified that body weight and alanine aminotransferase (ALT) had significant effects on azithromycin pharmacokinetics, yielding a 24% decrease of clearance in patients with ALT of >40. Monte Carlo simulation showed that for children with normal liver function, a loading-dose strategy (a loading dose of 15 mg/kg of body weight followed by maintenance doses of 10 mg/kg) would achieve the ratio of the area under free drug plasma concentration-time curve over 24 h (fAUC) to MIC90 (fAUC/MIC) target of 3 h in 53.2% of hypothetical patients, using a normative MIC susceptibility breakpoint of 2 mg/liter. For children with ALT of >40, the proposed dose needed to decrease by 15% to achieve comparable exposure. The corresponding risk of overdose for the recommended dosing regimen was less than 5.8%. In conclusion, the PPK of azithromycin was evaluated in children with CAP and an optimal dosing regimen was constructed based on developmental pharmacokinetic-pharmacodynamic modeling and simulation.

[Expression of interferon-λ1 in respiratory epithelial cells of children with RSV infection and its relationship with RSV load].

OBJECTIVE: To investigate the expression of IFN-λ1 in respiratory epithelial cells of children with respiratory syncytial virus (RSV) infection and its relationship with RSV load. METHODS: The nasopharyngeal swabs were collected from the children who were hospitalized with respiratory tract infection from June 2015 to June 2016. A direct immunofluorescence assay was used to detect the antigens of seven common respiratory viruses (including RSV) in the nasopharyngeal swabs. A total of 120 children who were only RSV positive were selected as the RSV infection group. A total of 50 children who had negative results in the detection of all viral antigens were selected as the healthy control group. Fluorescence quantitative real-time PCR was used to determine the RSV load and the expression of IFN-λ1 mRNA in the nasopharyngeal swabs of children in the two groups. RESULTS: The expression of IFN-λ1 in the RSV infection group was significantly higher than that in the healthy control group (P<0.05). The expression of IFN-λ1 was positively correlated with RSV load (r=0.56, P<0.05). CONCLUSIONS: RSV can induce the expression of IFN-λ1 in respiratory epithelial cells, suggesting that IFN-λ1 may play an important role in anti-RSV infection.

Effects of a novel photoactivated photosensitizer on MDR1 over-expressing human breast cancer cells.

Multidrug resistance (MDR) was the main reason of cancer chemotherapy failure. Photodynamic therapy (PDT) has been applied to the treatment of tumor and considered as a strategy for the overcoming of MDR phenomenon. Present study focused on a novel porphyrin-based photosensitizer DTP (meso-5-[p-diethylene triamine pentaacetic acid-aminophenyl]-10,15,20-triphenyl-porphyrin)-mediated photocytotoxicity on MDR1 highly expressing human breast cancer cell line MCF-7/ADR (adriamycin resistant) and the parental MCF-7 cell line. Experimental results indicated that DTP-PDT induced significant photocytotoxicity on MDR1 highly expressing MCF-7/ADR cell line, in spite of slightly weaker than on MCF-7 cell line, which was due to the relatively lower level of intracellular DTP in resistant MCF-7/ADR cells. Furthermore, intracellular DTP level in resistant MCF-7/ADR cells could not be altered with a Pgp inhibitor, verapamil and this indicated that DTP was not a possible substrate for the multidrug transporter Pgp. More importantly, photoactivated DTP could significantly reduce the expression of MDR1 gene at all the levels of mRNA, protein and function. The combined treatment with DTP-PDT and adriamycin was found to be more effective than adriamycin or DTP-PDT alone. In conclusion, our data demonstrated that DTP probably will be a potential photosensitizer in combating MDR phenomenon during the treatment of human breast cancer.

Association of Dietary Pattern during Pregnancy and Gestational Diabetes Mellitus: A Prospective Cohort Study in Northern China.

OBJECTIVE: To examine the association of maternal dietary patterns during pregnancy with gestational diabetes mellitus (GDM) in northern China. METHODS: The dietary intakes of pregnant women were recorded twice by 24-hour dietary recalls for three days prior to having been diagnosed with GDM, at 5-15 and 24-28 gestational weeks, respectively. GDM was diagnosed, and serum glycosylated hemoglobin (HbA1c) was measured at 24-28 weeks. Dietary patterns were assessed by factor analysis. The association of the dietary pattern with GDM and HbA1c was examined by multiple logistic models. RESULTS: Of 753 participants, 64 (8.5%) were diagnosed with GDM. Four dietary patterns were identified: Western pattern (dairy, baked/fried food and white meat), traditional pattern (light-colored vegetables, fine grain, red meat and tubers), mixed pattern (edible fungi, shrimp/shellfish and red meat) and prudent pattern (dark-colored vegetables and deep-sea fish). Compared with the prudent pattern, both the Western pattern and the traditional pattern were associated with an increased risk of GDM (aOR = 4.40, 95% CI: 1.58-12.22; aOR = 4.88, 95% CI: 1.79-13.32) and a high level of HbA1c (aOR = 12.37, 95% CI: 1.47-103.91; aOR = 26.23, 95% CI: 2.54-270.74). Compared to the lowest quartile (Q), Q3 of the Western pattern scores and Q3-Q4 of the traditional pattern scores were associated with a higher risk of GDM. CONCLUSION: The consumption of the Western pattern or the traditional pattern during pregnancy may increase the risk of GDM.

[Detection of cytochrome P450 3A4 gene polymorphism guides for labor analgesia with sufentanil medication].

OBJECTIVE: To investigate the relationship between single nucleotide polymorphisms (SNPs) of cytochrome P450 (CYP450) 3A4 rs2242480 and inter-individual differences of sufentanil consumption in accouchement sans douleur. METHODS: A total of 131 parturient women were collected. According to the distribution of genotypes and allele frequencies of rs2242480, the doses of sufentanil were individually designed. CC homozygotes were given the standard analgesia dose, CT heterozygotes and TT homozygotes were given 87.6% of standard sufentanil dose. RESULTS: Visual analogue score (VAS) between CC group and CT/TT group were 3.67±1.2 and 3.44±1.5, consistent with the expected analgesic standards. The difference was not statistically significant. CONCLUSION: The parturient women carrying CT heterozygotes and TT homozygotes of CYP3A4 rs2242480 required less sufentanil in accouchement sans douleur.

Clinical characteristics and mutation analysis of three Chinese children with autosomal recessive polycystic kidney disease.

BACKGROUND: There are few studies on the genotypes and phenotypes of autosomal recessive polycystic kidney disease in Chinese patients. METHODS: PKHD1 mutations in three children were detected with PCR and direct sequencing, and their clinical data were retrospectively reviewed. RESULTS: All of the children had bilateral enlarged polycystic kidneys, congenital hepatic fibrosis and intrahepatic bile duct dilatation. One of three children had classical multiple small cysts throughout the kidneys, and the other two children had bilateral multiple renal cysts of various sizes. Two children had abnormally shaped livers, portal hypertension and splenomegaly. Two heterozygous mutations (p.T36M, and p.P137S) were detected in Patient 1 and two were detected in Patient 2 (p.L2658X and p.V836A). One heterozygous mutation (p.L1425R) was detected in Patient 3. CONCLUSIONS: The study shows that renal and liver phenotypes of the Chinese children varied. Five mutations were identified in the three children, three of which were novel mutations.

[An improved method for generating integration-free human induced pluripotent stem cells].

The genome instability and tumorigenicity of induced pluripotent stem cells (iPSC) hinder their great potentials for clinical application. Using episomal vectors to generate iPSC is the best way to solve safety issues at present. This method is simple and the exogenous gene was not integrated into the host genome. However, the reprogramming efficiency for this method is very low and thus limits its usage. This study was purposed to improve episomal method for generating induced pluripotent stem cells from cord blood mononuclear cells (CB MNC), to establish integration-free iPSC technology system, and to lay the foundation for individualized iPSC for future clinical uses. To improve the reprogramming efficiency for iPSC, episomal method was used at various combinations of episomal vectors, pre-stimulating culture mediums and oxygen condition were tested to optimize the method. The results showed that using erythroid culture medium for culturing 8 days, transfecting with episomal vectors with SFFV (spleen focus forming virus) promoter under the hypoxic condition (3%), CB MNC could be mostly efficiently reprogrammed with the efficiency 0.12%. Furthermore, the results showed that erythroblasts (CD36(+)CD71(+)CD235a(low)) were the cells that are reprogrammed with high efficiency after culture for 8 days. It is concluded that a highly efficient and safe method for generation of integration-free iPSC is successfully established, which is useable in clinical study.

Contradictory imaging and EEG results in resection surgery of bitemporal lobe epilepsy: A case report.

The present study describes the case of a 27-year-old, right-handed female with bilateral mesial temporal lobe epilepsy. Electroencephalogram (EEG) monitoring from implanted electrodes displayed two different and independent onsets on the two sides of the mesial temporal structures, which specifically included clinical generalized tonic clonic seizure (GTCS) discharges originating from the left mesial temporal lobe, as well as complex partial seizure (CPS) discharges arising from the right mesial region. However, fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI) showed a unilateral abnormality, as in right mesial temporal lobe sclerosis. A decision was made to resect one side of the mesial temporal lobe, in order to avoid memory function impairment, and, relying on the MRI results, the right side was selected. However, surgery did not leave the patient seizure-free. The CPSs gradually eased, while the GTCSs originating from the left side became severely aggravated. In describing this case, the drawbacks of current epileptic diagnostic methods and surgical strategies for bitemporal lobe epilepsy are discussed, and the requirement for more treatment options is emphasized.

[Efficient reprogramming of human cord blood CD34(+) cells for formation of induced pluripotent stem cells with non-integrating plasmid system].

This study was to establish the episomal vector reprogramming method to reprogram iPSC from human cord blood (CB) CD34(+) cells. The non-integrating plasmids of pEB-C5 and pEB-Tg were transfected into short-term cultured CB CD34(+) cells by using the nucleofector, so as to demonstrate efficient reprogramming of CB CD34(+) cells. Within 14 days of one-time transfection by two plasmids together, up to 200 iPSC-like colonies per 2 million transfected CB CD34(+) cells were generated. The results showed that the pluripotency of iPSC-derived CB CD34(+) cells was similar to that of hESC and the karyotypes of iPSC were normal. In addition, no vector integration was found in iPSC of 9th and 10th passages. Furthermore, hiPSC formed teratoma with three embryonic germ layers. It is concluded that the integration-free method to generate human iPSC from CB CD34(+) cells is reliable and can provide new ways for both research and future clinical applications.

Investigation of membranous ventricular septal defect complicated with tricuspid regurgitation in ventricular septal defect occlusion.

This study aimed to explore the mechanism of membranous ventricular septal defect complicated with tricuspid regurgitation and the significance of ventricular septal defect occlusion by echocardiography. A total of 43 patients with membranous ventricular septal defect complicated with tricuspid regurgitation were observed by echocardiography and the changes in length, area and volume of tricuspid regurgitation prior to and following ventricular septal defect occlusion were measured. There were four different mechanisms of membranous ventricular septal defect complicated with tricuspid regurgitation. The various indices of tricuspid regurgitation volume were significantly reduced following occlusion. Ventricular septal defect occlusion significantly reduces tricuspid regurgitation volume complicated with membranous ventricular septal defect and echocardiography is an ideal method to detect these changes.

Pulsed laser deposition of ITO/AZO transparent contact layers for GaN LED applications.

In this study, indium-tin oxide (ITO)/Al-doped zinc oxide (AZO) composite films were fabricated by pulsed laser deposition and used as transparent contact layers (TCLs) in GaN-based blue light emitting diodes (LEDs). The ITO/AZO TCLs were composed of the thin ITO (50 nm) films and AZO films with various thicknesses from 200 to 1000 nm. Conventional LED with ITO (200 nm) TCL prepared by E-beam evaporation was fabricated and characterized for comparison. From the transmittance spectra, the ITO/AZO films exhibited high transparency above 90% at wavelength of 465 nm. The sheet resistance of ITO/AZO TCL decreased as the AZO thickness increased, which could be attributed to the increase in a carrier concentration, leading to a decrease in the forward bias of LED. The LEDs with ITO/AZO composite TCLs showed better light extraction as compared to LED with ITO TCL in compliance with simulation. When an injection current of 20 mA was applied, the output power for LEDs fabricated with ITO/AZO TCLs had 45%, 63%, and 71% enhancement as compared with those fabricated using ITO (200 nm) TCL for the AZO thicknesses of 200, 460, and 1000 nm, respectively.

[Detection of Coxsackie B3 virus infection in newborn care unit using reverse transcriptase polymerase chain reaction method].

OBJECTIVE: To explore the sensitivity of reverse transcriptase polymerase chain reaction (RT-PCR) method for detection of Coxsackie virus B3 (CoxB3) infection. METHODS: RT-PCR method was used to detect CoxB3 viral RNA in peripheral blood samples of 31 sick children and their mothers (62 cases) from a single hospital. RESULTS: Among the 62 samples taken from 31 sick children and their mothers, the serological test showed only one positive case in anti-Coxsackie virus IgM. The CoxB3 serological positive rate was 1.61%. The results of RT-PCR method showed that among the 62 samples there were 12 positive cases and the positive rate was 19.35%; both mothers and children were positive in four pairs of the samples (8 cases), suggesting vertical viral transmission; two cases of neonatal were positive with their mothers negative; two cases of mothers were positive with their newborns negative. CONCLUSION: RT-PCR is a rapid, sensitive and specific method for detection of CoxB3 infection and its positive rate is superior to serological method.

[High-risk factors and clinical pathological analysis in 21 cases of fatal pulmonary embolism].

OBJECTIVE: To explore the clinical and pathological characteristics of fatal pulmonary thromboembolism, especially the contribution of acquired and genetic risk factors of fatal pulmonary thromboembolism, so as to provide some useful information for its clinical prevention and treatment. METHODS: The medical dispute autopsy cases performed at the Department of Pathology, School of Basic Medical Sciences, Peking University from January 1, 2002 to September 30, 2008 were retrospectively reviewed. FV ( factor V ) Leiden mutation and FII ( factor II) G20210A mutation were analyzed by using methods of PCR and restriction fragment length polymorphism (RFLP) in fatal pulmonary embolism cases and random selected control cases of adult autopsy. RESULTS: There were 21 patients who died from fatal pulmonary thromboembolism, accounting for 12.96% (21/162) of adult autopsy cases. In these cases, there was at least one of the known risk factors in each case and more than two risk factors could be found in most cases. The acquired risk factors, such as surgery, trauma and fractures, cancer, pregnancy and puerperium, the elderly, hypertension, diabetes, infections, could be found in these patients. FV Leiden mutation and FII G20210A mutation were not detected in any of the 21 cases of fatal pulmonary thromboembolism cases and six control cases. Of all the 21 cases, quantitative D-dimer measurement was performed only in six patients and D-dime level in these six samples was all significantly increased. According to the records, there was only 1 patient treated by preventive anticoagulants in the 21 patients. CONCLUSION: Fatal pulmonary thromboembolism is an important reason for medical dispute. Fractures and trauma, surgery and other acquired factors are the main reasons for fatal pulmonary embolism in Chinese. Genetic factors (FV Leiden and FII G20210A mutations) are not the reason for Chinese to suffer from fatal pulmonary thromboembolism. Assessment of risk factors (especially traumatic fractures and surgical intervention) of pulmonary thromboembolism may play an important role in taking appropriate preventive procedures, early diagnosis and reasonable treatment to reduce its mortality.

[Clinical and biopsy-based myopathological features of 5 cases with centronuclear myopathy].

OBJECTIVE: To analyze the clinical and pathological features of the centronuclear myopathy (CNM) in 5 Chinese patients and evaluate their diagnostic and differential diagnostic value. METHODS: A standard series of histochemical and enzymohistochemical investigations were performed on all muscle specimens of CNM cases obtained via biopsy. The clinical manifestations and myopathological features of 5 CNM patients were retrospectively analyzed. RESULTS: The age of onset ranged from 3 to 12 years. All patients primarily presented with limb girdle muscle weakness. In 3 patients extraocular muscles, facial muscles and cervical muscles were affected, respectively. The proximal muscles were affected more seriously than the distal and the lower limbs more seriously than the upper. Tendon reflex was reduced and no evident muscular atrophy was seen. The course of the disease ranged from 4 to 46 years and progressed slowly. The ability of walking could be maintained for many years and the fast movements such as running and jumping were impaired early. The serum creatine kinase (CK) level was normal or elevated slightly. Electromyography showed myopathic pattern in all cases. Two patients (mother and son) were from the same family and the son's two siblings had similar symptoms indicating autosomal dominant inherited pattern. There was mild variation in fiber size and most small fibers were round. Interstitial tissue increase slightly. Fibers with centrally placed nuclei accounted for 23% - 93%. Neither necrotic and regenerated fibers nor infiltration of inflammatory cells were seen. Type I fiber predominance and hypotrophy were present in all patients. Abnormal arrangement of the sarcoplasmic strands in appearance of "spokes of a wheel", increased oxidative enzyme activity around centronuclear and perinuclear halo were observed in 2 patients by NADH-TR staining. CONCLUSIONS: For the patients who had the onset during the childhood and presented with slow progressive limb girdle muscle weakness, disability of fast movements and normal serum CK level, the possibility of benign congenital myopathy should be considered. High percentage of centronuclear fibers as well as type I fiber predominance and hypotrophy in muscle biopsy pathology may provide a morphological evidence for the definite diagnosis of CNM.

[Clinical and pathological features and prognosis of Chinese patients with distal myopathy with rimmed vacuoles: study of 17 cases].

OBJECTIVE: To clarify the clinical and pathological features and prognosis of Chinese patients with distal myopathy with rimmed vacuoles (DMRV). METHODS: The clinical data of 17 Chinese DMRV patients with the courses of disease of 1-21 years, 5 males and 12 females, aged 28.9 (19-41), were collected. Biopsy of muscle specimens of 17 Chinese DMRV patients were summarized retrospectively. Muscle specimens were collected from the biceps brachii, tibialis anterior, gastrocnemius, or quadriceps femoris and underwent light microscopy. Eight muscle specimens underwent electron microscopy. 11 patients were followed up for 4 months to 15 years. RESULTS: The age of onset ranged from 5 to 40 years (averaging 23 years). Distal muscle weakness and atrophy of the lower extremities, especially anterior tibial muscle, was predominant in the early stage. Proximal and trunk muscles were involved in the advanced stage. Quadriceps femoris were slightly involved. The striking and characteristic pathological finding was the presence of rimmed vacuoles in atrophic muscle fibers with little evidence of necrotic or regenerative processes. Electron microscopy showed accumulation of myeloid structure and cytoplasmic or intranuclear tubofilamentous inclusion bodies. Although atrophy and weakness of the leg muscle appeared as initial symptoms, severe generalized skeletal muscle involvement with sparing of the facial, extraocular, bulbar, intercostals, and diaphragm muscles was recognized in the advanced stage. The patients became non-ambulant about 7-10 years after the onset of the disease. They lost the self-care ability and the quality of their life was rather low. CONCLUSION: The clinical and pathological features of the Chinese DMRV patients are basically similar to those of the Japanese patients. With the disease progressing slowly, the patients become wheelchair-bound and lose the self-care ability. As to daily life, the prognosis of DMRV is extremely poor.