Exploration of urine metabolic biomarkers for new-onset, untreated pediatric epilepsy: A gas and liquid chromatography mass spectrometry-based metabolomics study.

OBJECTIVE: The discovery of objective indicators for recent epileptic seizures will help confirm the diagnosis of epilepsy and evaluate therapeutic effects. Past studies had shortcomings such as the inclusion of patients under treatment and those with various etiologies that could confound the analysis results significantly. We aimed to minimize such confounding effects and to explore the small molecule biomarkers associated with the recent occurrence of epileptic seizures using urine metabolomics. METHODS: This is a multicenter prospective study. Subjects included pediatric patients aged 2 to 12 years old with new-onset, untreated epilepsy, who had had the last seizure within 1 month before urine collection. Controls included healthy children aged 2 to 12 years old. Those with underlying or chronic diseases, acute illnesses, or recent administration of medications or supplements were excluded. Targeted metabolome analysis of spot urine samples was conducted using gas chromatography (GC)- and liquid chromatography (LC)-tandem mass spectrometry (MS/MS). RESULTS: We enrolled 17 patients and 21 controls. Among 172 metabolites measured by GC/MS/MS and 41 metabolites measured by LC/MS/MS, only taurine was consistently reduced in the epilepsy group. This finding was subsequently confirmed by the absolute quantification of amino acids. No other metabolites were consistently altered between the two groups. CONCLUSIONS: Urine metabolome analysis, which covers a larger number of metabolites than conventional biochemistry analyses, found no consistently altered small molecule metabolites except for reduced taurine in epilepsy patients compared to healthy controls. Further studies with larger samples, subjects with different ages, expanded target metabolites, and the investigation of plasma samples are required.

Stereomicroscopic features of colitis-associated tumors in mice: Evaluation of pit pattern.

Patients with longstanding ulcerative colitis have an increased risk of colorectal cancer. Mouse models for colitis-associated tumors are indispensable for the development of novel strategies for prevention and intervention, as well as an improved understanding of the mechanisms underlying tumor formation. The present study examined whether stereomicroscopic observations with dye-application were able to detect and discriminate tumors in a colitis-associated tumor model in mice. Colonic tumors were induced in C57BL/6 mice by 15 cycles of treatment with dextran sulfate sodium (DSS) in drinking water. The mice were then divided into 4 groups: normal mice fed a control diet, normal mice fed an iron-supplemented diet, 0.7% DSS mice fed an iron diet and 1.5% DSS mice fed an iron diet. The entire colons were characterized with respect to both morphology and histology. The pit pattern architecture was analyzed using stereomicroscopy with dye agents (0.2% indigo carmine or 0.06% crystal violet). The tumor histology was graded as negative, indefinite or positive for dysplasia. The positive category was divided into two subcategories: low-grade dysplasia (LGD) and high-grade dysplasia (HGD). The tumor incidences and multiplicity were significantly higher in mice fed an iron diet and 1.5% DSS compared with in mice fed an iron diet and 0.7% DSS. Compared with LGD, HGD was predominantly located in the distal colon, was larger in size and had a higher incidence of elevated lesions (Is and IIa) and a lower incidence of flat lesions (IIb). In regards to the pit pattern, HGD had a high incidence of VI pits and a low incidence of IV, IIIL and II pits. In conclusion, evaluation of the pit pattern using stereomicroscopy with dye-application is useful for detecting and discriminating neoplastic changes in DSS mice and may further our understanding of the mechanisms that induce tumor formation in patients with ulcerative colitis and the characterization of pharmaceutical responses.

Important role of calcium chloride in preventing carbon monoxide generation during desflurane degradation with alkali hydroxide-free carbon dioxide absorbents.

We investigated whether calcium chloride (CaCl2), a supplementary additive in carbon dioxide (CO2) absorbents, could affect carbon monoxide (CO) production caused by desflurane degradation, using a Japanese alkali-free CO2 absorbent Yabashi Lime®-f (YL-f), its CaCl2-free and 1% CaCl2-added derivatives, and other commercially available alkali-free absorbents with or without CaCl2. The reaction between 1 L of desflurane gas (3-10%) and 20 g of desiccated specimen was performed in an artificial closed-circuit anesthesia system for 3 min at 20 or 40 °C. The CO concentration was measured using a gas chromatograph equipped with a semiconductor sensor detector. The systems were validated by detecting dose-dependent CO production with an alkali hydroxide-containing CO2 absorbent, Sodasorb®. Compared with YL-f, the CaCl2-free derivative caused the production of significantly more CO, while the 1% CaCl2-added derivative caused the production of a comparable amount of CO. These phenomena were confirmed using commercially available absorbents AMSORB® PLUS, an alkali-free absorbent with CaCl2, and LoFloSorb™, an alkali-free absorbent without CaCl2. These results suggest that CaCl2 plays an important role in preventing CO generation caused by desflurane degradation with alkali hydroxide-free CO2 absorbents like YL-f.

A randomized controlled trial comparing paravertebral block via the surgical field with thoracic epidural block using ropivacaine for post-thoracotomy pain relief.

PURPOSE: We conducted a comparative study to evaluate analgesic efficacy between paravertebral block via the surgical field (PVB-sf), in which the catheter was inserted into the ventral side of the sympathetic trunk in the paravertebral space by a thoracic surgeon under thoracoscopic visualization, and epidural block (Epi) using ropivacaine for post-thoracotomy pain relief. METHODS: Lung cancer patients scheduled for lobectomy via thoracotomy were randomly allocated to receive either PVB-sf or Epi (n = 36 per group). Before thoracotomy closure, 0.375% ropivacaine was administered as a bolus (PVB-sf, 20 mL; Epi, 5 mL), followed by a 300-mL continuous infusion of 0.2% ropivacaine at 5 mL/h. Postoperative pain was assessed using a visual analog scale (VAS) score at various time points, including the primary endpoint of 2 h after ropivacaine bolus injection. Sensory block area, vital signs, serum ropivacaine concentrations, and side effects were also evaluated. RESULTS: The Epi group showed significantly lower VAS scores and blood pressure and a wider sensory block area than the PVB-sf group at all evaluation time points. While the mean serum ropivacaine concentration in the PVB-sf group was significantly higher than that in the Epi group until 1 h after injection of the ropivacaine bolus, there was no significant difference at any subsequent assessment point. The incidence of side effects was similar between the groups. CONCLUSION: The Epi was superior to PVB-sf for the management of post-thoracotomy pain in this patient cohort. The number of dermatomes anaesthetized by Epi was greater than that anaesthetized by PVB-sf. No difference in complication rates was observed between the two groups.

[The effects of pulmonary rehabilitation in elderly patients].

Pulmonary rehabilitation is one of the most important treatment modalities for patients with chronic lung disease. To determine the effects of an outpatient pulmonary rehabilitation program for the older members (aged 77 +/- 3 years; seniors) of an elderly patient group with chronic lung disease, we prospectively compared the degrees of improvement of lung function, dyspnea, daily activities and exercise tolerance (6-minute walking distance) after a 9-week rehabilitation program in 27 seniors with chronic lung disease (COPD 18, post-tuberculosis lung disorders 8, lung fibrosis 1; %FEV1 50.9 +/- 17.1%) with that in disease- and %FEV1-matched younger members (aged 70 +/- 2 years; juniors; %FEV1 49.3 +/- 16.1%) of the elderly patient group. All patients performed supervised weekly outpatient exercise and education activities for 9 weeks and a home exercise regimen. Assessments were made before and after the program. Twenty-three of the seniors and 25 of the juniors completed the program. There was no significant difference in the withdrawal rates between these groups. Although lung function and blood gas data had not changed significantly after rehabilitation, the clinical symptoms and the 6-minute walking exercise improved significantly in both groups (Baseline Dyspnea Index focal score: +1.3 +/- 0.9 in the seniors and +0.6 +/- 0.9 in the juniors: 6-minute walking distance: +/- 52 m and +/- 62 m, respectively) and the improvement of the Baseline Dyspnea Index focal score was significantly greater in the seniors than in the juniors. We observed the patients after they had followed the program for 2,000 days and found that the continuation ratio of rehabilitation in the seniors was far inferior to that in the juniors (continuation ratios for 1.2 and 3 years in the seniors were 50.5, 18.0 and 0%, respectively, and in the juniors, 79.5, 66.2 and 61.5%). We concluded that, although the senior elderly patients could benefit from the pulmonary rehabilitation program, it is difficult to maintain this benefit for many years.