BackgroundSeizures are one of the most important neurological complications of bacterial brain abscesses. A better understanding of the risk factors of seizures following bacterial brain abscesses is ...needed to predict those who will require treatment.MethodsA total of 205 patients were enrolled in this 22-year retrospective study. Prognostic variables were analysed based on Cox's proportional hazards model after a minimum of 18 months of follow-up.ResultsSeizures occurred in 48 patients who had bacterial brain abscesses, including acute symptomatic seizures in 17% (35/205) and unprovoked seizures in 6.4% (13/205). Altogether, 27 patients had early seizures and 21 had late seizures. The overall mortality rate in the seizure patients was 23% (11/48) and seven patients progressed to epilepsy.ConclusionCox's proportional hazards model demonstrated that valvular heart diseases as the underlying diseases and the presence of a fronto-parietal distribution of bacterial brain abscess were independently predictive of seizures, and the presence of late seizures was predictive of developing epilepsy. Most first seizures occurred within 3 y after bacterial brain abscesses.
The clinical data of 62 adult patients who suffered post-neurosurgical nosocomial bacterial meningitis, retrospectively collected over a 16-year period, were studied. Cases were divided into two ...groups based on the date of presentation, the first period being 1986–1993 and the second 1994–2001. Fever and progressive consciousness disturbance were the most consistent clinical features - signs that may also be attributed to other postoperative neurosurgical problems. The common pathogens included
Staphylococcus aureus, coagulase negative
Staphylococcus,
Pseudomonas aeruginosa,
Escherichia coli, and
Acinetobacter baumannii. An increase in polymicrobial infections and multi-antibiotic resistance during the second period was identified. In the first half of the study, mortality was 22%, and in the second half 36%. Adult post-neurosurgical nosocomial bacterial meningitis has become an important clinical problem. The choice of appropriate empirical antibiotics is challenging and must be guided by an awareness of the relative frequency of various pathogens and the increasing incidence of resistant strains. Although high mortality rates may, in part, be related to the primary brain pathology, early diagnosis and the timely use of antibiotics based on antimicrobial susceptibility testing are essential for survival.
Hyperbaric oxygen (HBO) therapy has been proved in improving bone healing, but its effects on mesenchymal stem cells (MSCs) in vivo is not clear. The aims of this study are to clarify whether the HBO ...therapy has the same enhancing effect on MSCs with regard to bone formation and maturation and to ascertain whether the transplanted MSCs survive in the grafted area and contribute to new bone formation.
Twenty-three adult rabbits underwent posterolateral fusion at L4-L5 level. The animals were divided into three groups according to the material implanted and subsequent treatment: (1) Alginate carrier (n = 6); (2) Alginate-MSCs composite (n = 11); and (3) Alginate-MSCs composite with HBO therapy (n = 6). After 12 weeks, spine fusion was examined using radiographic examination, manual testing, and histological examination. Using a PKH fluorescence labeling system, whether the transplanted MSCs survived and contributed to new bone formation in the grafted area after HBO therapy was also examined.
The bilateral fusion areas in each animal were evaluated independently. By radiographic examination and manual palpation, union for the Alginate, Alginate-MSCs, and Alginate-MSCs-HBO groups was 0 of 12, 10 of 22, and 6 of 12 respectively. The difference between the Alginate-MSCs and Alginate-MSCs-HBO groups was not significant (P = 0.7997). The fluorescence microscopy histological analysis indicated that the transplanted PKH67-labeled MSCs survived and partly contributed to new bone formation in the grafted area.
This study demonstrated that the preconditioned MSCs could survive and yield bone formation in the grafted area. HBO therapy did not enhance the osteogenic ability of MSCs and improve the success of spine fusion in the rabbit model. Although there was no significant effect of HBO therapy on MSCs for spine fusion, the study encourages us to research a more basic approach for determining the optimal oxygen tension and pressure that are required to maintain and enhance the osteogenic ability of preconditioned MSCs. Further controlled in vivo and in vitro studies are required for achieving a better understanding of the effect of HBO treatment on MSCs.
The purpose of this study was to compare the bond strengths and debonded interfaces achieved with light-cured resin-modified glass ionomer cement (RMGIC) and conventional light-cured composite resin. ...In addition, the effects of acid etching and water contamination were examined. One hundred human premolars were randomly divided into five equal groups. The mini Dyna-lock upper premolar bracket was selected for testing. The first four groups were treated with light-cured RMGIC with or without 15 per cent phosphoric acid-etching treatment and with or without water contamination preceding bracket bonding. The control samples were treated with the conventional light-cured Transbond composite resin under acid etching and without water contamination. Subsequently, the brackets were debonded by tensile force using an Instron machine. The modified adhesive remnant index (ARI) scores were assigned to the bracket base of the debonded interfaces using a scanning electron microscope. The bond strength and modified ARI scores were determined and analysed statistically by one-way analysis of variance and chi-square test. Under all four conditions, the bond strength of the light-cure RMGIC was equal to or higher than that of the conventional composite resin. The highest bond strength was achieved when using RMGIC with acid etching but without water contamination. The modified ARI scores were 2 for Fuji Ortho LC and 3 for Transbond. No enamel detachment was found in any group. Fifteen per cent phosphoric acid etching without moistening the enamel of Fuji Ortho LC provided the more favourable bond strength. Enamel surfaces, with or without water contamination and with or without acid etching, had the same or a greater bond strength than Transbond.
This retrospective chart review describes the clinical features, pathogens, and outcomes of 46 patients with cerebrospinal fluid (CSF) shunt infections collected over 16 years. The overall CSF shunt ...infection rate was 2.1%, broken down into 1.7 and 9.3% in adult and pediatric groups, respectively. Fever and progressive consciousness disturbance were the most clinical features in the adult patient group, whereas disturbance of consciousness and abdominal symptoms and signs were the two most common clinical features in the pediatric patient group. The most frequently isolated microorganisms were of the Staphylococcus spp., including Staphylococcus aureus and coagulase negative Staphylococcus, which accounted for 47% of the episodes. Furthermore, increases in polymicrobial and Gram-negative bacilli infections were observed in our study. Due to the high proportion of oxacillin-resistant Staphylococcus spp. and polymicrobial infections, we recommend initial empirical antibiotics with both vancomycin and a third-generation cephalosporin for cases in which the causative bacteria has not been identified or for which the results of antimicrobial susceptibility tests are not available. For patients who develop smoldering fevers, progressive disturbed consciousness, seizures, or abdominal fullness after ventriculoperitoneal shunt procedures, CSF shunt infections should be suspected. Although some infections have been managed successfully with antimicrobial therapy alone, the timely use of appropriate antibiotics according to antimicrobial susceptibility testing and the removal of the shunt apparatus are essential for successful treatment.
Purpose: A prospective population‐based case‐control study was performed to ascertain whether febrile convulsion (FC) in early childhood is associated with neurocognitive attention deficits in school ...age.
Methods: A total of 103 children, confirmed to have FC by age 3 years from a population survey of 4,340 live‐birth new‐borns in Tainan City, Taiwan, was followed up until at least age 6 years. An achievement test, behavioral ratings, and computerized neurocognitive battery assessing various subcomponents of attention were given to 87 FC children (FC group) and 87 randomly selected population‐matched control (CC group).
Results: Compared with the CC group, the FC group did not have scholastic performance or behavioral outcome disadvantage. Overall FC group performance was distinguished by significantly higher scores in the achievement test and fewer missing errors (p <0.005) and commission errors (p <0.05), less variability in reaction time (p <0.005), and a nonsignificant trend of impulsivity. Attention performance of the FC and CC groups were comparable. Within the FC group, age at onset, complex FC, recurrence of FC, development of unprovoked seizures, or prior use of phenobarbital had no adverse effects on neurocognitive attention outcome.
Conclusions: This population study suggests that FC in early childhood does not have adverse effects on behavior, scholastic performance, and neurocognitive attention. On the contrary, the FC group demonstrated significantly better control of distractibility and attention at school age.
Vinorelbine (VNB) is a member of vinca alkaloid medications and approved for the treatment of non-small cell lung cancer as well as off-label use for metastatic breast cancer over 20 years based upon ...FDA-approved indication. Several studies have suggested the potential of VNB in treating sarcomas. Liposomal VNB (TLC178) is a novel sustained release liposomal formulation. In the presented studies, TLC178 resulted in enhanced tumor accumulation and greater anti-tumor efficacy than non-liposomal VNB.
Mice were subcutaneously inoculated with human sarcoma cell lines (1.5∼4×106/mouse) at the dorsal-lateral flank. Treatment was commenced once tumor size reached 150 to 400mm3 in average. Mice were intravenously (i.v.) injected with test articles by groups.Table1722PTableStudy #Cell Type Cell DensityInitial Tumor Size (mm3)Treatment Group (Dosage)Dosing RegimenPD17060Human Rhabdomyo- sarcoma (RMS) cell line (SJCRH30) 1.5×106/mouse200Saline TLC178 (5mg/kg) VNB solution (5mg/kg)TLC178 and VNB were injected at a 4-day interval for three doses.PD17069Human RMS cell line (SJCRH30) 4×106/mouse150Saline TLC178 (7.5mg/kg) VNB solution (10mg/kg) + cyclophosphamide (CTX) (19.8mg/kg)TLC178 and VNB were injected once weekly for two doses while CTX was administrated at 19.8mg/kg on day 0, 7 and 50mg/kg on day 8.PD17008Human fibrosarcoma cell line (HT1080) 2.2×106/mouse390D5W TLC178 (5mg/kg) Doxorubicin (3.4mg/kg)TLC178 and doxorubicin were injected at a 4-day interval for two doses.PK17066Human RMS cell line (SJCRH30) 2.3×106/mouse150 to 400TLC178 (5mg/kg) TLC178 (10mg/kg) VNB solution (10mg/kg)Single injection*Tumor size was monitored with digital caliper during the study. * Plasma and tumors were collected to determine VNB concentration in bio-distribution study. * Saline or D5W (Dextrose 5% in Water) was used as the control group according to the study design. * VNB solution is vinorelbine injectable solution
In efficacy studies (Study #PD17060, #PD17069 and #PD17008), TLC178 not only showed better inhibitory effect than that of VNB alone and VNB+CTX treatments in the SJCRH30 RMS xenograft model, but also remarkably suppressed HT1080 human fibrosarcoma compared with doxorubicin, an approved drug for treatment of sarcomas. In a biodistribution study (Study #PK17066), TLC178 yielded larger systemic exposure of total VNB (comprising liposome-encapsulated and unencapsulated VNB), higher local concentration and longer elimination half-life in tumor compared to VNB.
TLC178 demonstrated improved in vivo systemic VNB PK profile and tumor distribution, which resulted in superior anti-cancer efficacy compared to traditional VNB treatment. Therefore, TLC178 may have potential as a single or combination treatment for sarcomas with decreased dosage and/or frequency, reduced toxicity, and enhanced efficacy.
Taiwan Liposome Company, Ltd.
Has not received any funding.
All authors have declared no conflicts of interest.
Infection with rhinovirus (RV) triggers exacerbations of asthma and chronic obstructive lung disease.
We sought to develop a mouse model of RV employing RV1B, a minor group serotype that binds to the ...low-density lipoprotein receptor.
C57BL/6 mice were inoculated intranasally with RV1B, replication-deficient ultraviolet (UV)-irradiated RV1B, or RV39, a major group virus.
Viral RNA was present in the lungs of RV1B-treated mice, but not in those exposed to UV-irradiated RV1B or RV39. Lung homogenates of RV-treated mice contained infectious RV 4 days after inoculation. RV1B exposure induced neutrophilic and lymphocytic airway inflammation, as well as increased lung expression of KC, macrophage-inflammatory protein-2, and IFN-alpha and IFN-beta. RV1B-exposed mice showed airway hyperresponsiveness 1 and 4 days after inoculation. UV-irradiated RV1B induced modest neutrophilic airway inflammation and hyperresponsiveness 1 day after exposure. Both RV1B and UV-irradiated RV1B, but not RV39, increased lung phosphorylation of Akt. Confocal immunofluorescence showed colocalization of RV1B and phospho-Akt in the airway epithelium. Finally, pretreatment with the phosphatidylinositol 3-kinase inhibitor LY294002 attenuated chemokine production and neutrophil infiltration.
We conclude that RV1B induces airway inflammation in vivo. Evidence is presented that viral replication occurs in vivo and is required for maximal responses. On the other hand, viral replication was not required for a subset of RV-induced responses, including neutrophilic inflammation, airway hyperresponsiveness, and Akt phosphorylation. Finally, phosphatidylinositol 3-kinase/Akt signaling is required for maximal RV1B-induced airway neutrophilic inflammation, likely via its essential role in virus internalization.