The Efficacy of Carotid Tubercle as an Anatomical Landmark for Identification of Cervical Spinal Level in the Anterior Cervical Surgery: Comparison with Preoperative C-arm Fluoroscopy

Background

In cervical anterior approach, transverse skin incision is preferred due to cosmetic reasons. Precise skin incision is required to reach the surgery segment while minimizing soft tissue injury. Skin incision site is frequently identified using C-arm fluoroscopy or the carotid tubercle. Accordingly, this study was conducted to investigate the efficacy of skin incision using the carotid tubercle as a marker.

Methods

This study was retrospectively conducted on 114 patients who underwent anterior cervical surgery by the same surgeon from April 2004 to June 2012. The rate of the appropriate insertion of K-wire, which was inserted into the disc after anterior approach, into the surgery segment was compared between 62 patients where skin incision site was identified using C-arm fluoroscopy before skin incision and 52 patients where skin incision site was identified using carotid tubercle palpitation before surgery.

Results

The needle was shown to have been inserted into the planned site in 106 patients out of the total 114 patients. The appropriate insertion of the needle was shown in 59 patients of group I (95.2%) and in 47 patients of group II (90.4%). Although the success rate was higher in group I than group II, it was statistically insignificant. The success rate of one-segment surgery was shown to be 89.7% in group I and 82.6% in group II. Although the success rate was higher in group I than group II, it was statistically insignificant. The success rate of two-segment surgery was shown to be 100% in group I, and 96.4% in group II due to one case of the failure at C3-4 and C5-6. The success rate of three- and four-segment surgeries was shown to be 100% in both groups.

Conclusions

The identification of skin incision site via carotid tubercle palpation was useful for surgeries involving two or more segments. Furthermore, it could be useful for one-segment surgery if surgical site is identified using vertebral body or soft tissues such as longus collis rather than insertion into the disc.     

Pharmacokinetic and pharmacodynamic evaluation of a novel proton pump inhibitor, YH1885, in healthy volunteers

To evaluate the pharmacokinetic and pharmacodynamic characteristics of YH1885, a novel proton pump inhibitor, a single-blind, randomized, placebo-controlled, dose-rising, parallel-group study was conducted in 46 healthy volunteers. The volunteers were randomly allocated to single dose groups of 60 mg, 100 mg, 150 mg, 200 mg, and 300 mg (6 subjects per dose, including 2 placebos) or to multiple-dose groups of 150 mg and 300 mg (once-daily dosing for 7 days; 8 subjects per dose, including 2 placebos). The multiple-dose study was conducted separately after the single-dose study. YH1885 was administered orally after overnight fasting. Serial blood samples, urine samples, and pharmacodynamic measurements were taken. Drug concentrations in plasma and urine were determined by liquid chromatography/mass spectrometry (LC/MS). Pharmacodynamic changes were evaluated by ambulatory intragastric pH monitoring and by serial measurements of serum gastrin concentrations. Assessments of safety and tolerability also were made. Plasma concentrations of YH1885 reached peak levels 1.3 to 2.5 hours after single-dose administration and then declined monoexponentially with a terminal half-life (t(1/2)) of 2.2 to 2.4 hours in dosage groups up to 200 mg in the single-dose study. YH1885 showed linear pharmacokinetic characteristics, and little accumulation occurred after multiple administrations. The parent drug was not detected in urine. Dose-related pharmacological effects were obvious for dose groups of 150 mg and higher in the single-dose study. The mean intragastric pH and the percentage of time at pH>4 were significantly increased. The onset of drug effect was rapid, and maximal effects were observed on the first day of administration during multiple dosing. Serum gastrin levels also showed rapid increases during dosing but with a weak dose-effect relationship. Neither serious nor dose-limiting adverse effects were observed. YH1885 was found to be safe and well tolerated and effectively inhibited acid secretion with dose-dependent increases in intragastric pH. The acid-suppressing efficacy of YH1885 needs to be further evaluated in patients with gastric acid-related diseases.     

Increased expression of metallothionein is associated with irinotecan resistance in gastric cancer

To gain insight into clinically relevant mechanisms of irinotecan resistance, we undertook oligonucleotide microarray analyses on paired malignant effusion samples obtained from eight gastric cancer patients treated with weekly irinotecan. Pretreatment and posttreatment (48 h) effusion samples were obtained for each patient, and the change in expression profile was compared between clinical responders and nonresponders. When differences in the expression of genes were examined using SAM (Significance Analysis of Microarrays) software, five isoforms of the metallothionein family were identified to have significantly higher signal log ratios in five nonresponders, compared with three responders. Compared with control cells, metallothionein 1X (MT1X)-transfected AGS cells showed a 1.4-fold higher irinotecan IC(50) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and tended to form more colonies. These findings collectively suggest that irinotecan-induced up-regulation of metallothionein might be associated with irinotecan resistance in patients with gastric cancer, although it remains to be confirmed in a larger data set.     

The expression of DNA damage checkpoint proteins and prognostic implication in metastatic brain tumors

The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, DNA damage checkpoint signaling pathway activation after irradiation has received increasing attention. The association between the expression levels and survival outcome was evaluated to find possible therapeutic targets in brain metastasis. Radiosensitivity of human non-small cell lung cancer cell lines was determined by checking their viability after treatment with varying doses of ionizing radiation (IR). The expression of DNA checkpoint proteins was analyzed by Western blots and immunohistochemistry. On the basis of the clinical data for the patients, the association between the expression of the components and patients' survival was investigated. The expression levels of TopBP1 and phosphorylated Chk1 (P-Chk1) protein were higher in radioresistant lung cancer cell lines compared to radiosensitive cell lines. We previously assessed radiation survival of lung cancer cell lines after treating them with Chk1 inhibitor, AZD7762. AZD7762 significantly sensitized both radioresistant and radiosensitive cells to IR. We also observed a strong inverse relationship between progression-free survival (PFS) and expression level of P-Chk1 and TopBP1. This study, which is the first clinical report that connects DNA damage checkpoints and prognosis of brain metastasis, supports these two proteins to be promising targets for overcoming the radioresistance in brain metastasis.     

A variant 2677A allele of the MDR1 gene affects fexofenadine disposition

BACKGROUND AND OBJECTIVES: There have been considerable disagreements regarding the influence of MDR1 (ABCB1) polymorphisms on the disposition of P-glycoprotein (P-gp) substrates. We speculated that the unknown function of the A allele of exon 21 G2677T/A (Ala893Ser/Thr) provides one of the reasons for the contradictory results. This study was performed to clarify the effects of major MDR1 gene polymorphisms, including a variant A allele in exon 21, on fexofenadine pharmacokinetics. METHODS: We investigated the occurrence of 3 high-frequency single-nucleotide polymorphisms (SNPs) in exons 12 (C1236T), 21 (G2677T/A), and 26 (C3435T) of the MDR1 gene in 232 healthy Koreans, using a polymerase chain reaction-restriction fragment length polymorphism method, and performed haplotype analysis on these 3 SNPs. A single oral dose of 180 mg fexofenadine hydrochloride was administered to 33 healthy Korean male volunteers, who were divided into 6 groups based on the MDR1 genotype for the G2677T/A polymorphism in exon 21 and the C3435T polymorphism in exon 26. RESULTS: A strong linkage disequilibrium was observed among the 3 SNPs. The frequencies of the 4 major haplotypes, 1236C-2677A-3435C, C-G-C, T-G-C, and T-T-T, were 16.4%, 18.6%, 21.6%, and 32.2%, respectively. Fexofenadine disposition varied considerably among the groups. In the 2677AA/3435CC genotype group (n=3), the values of area under the concentration-time curve from time 0 to 24 hours [AUC(0-24)] were significantly lower (P=.014) than those of the other 5 genotype groups (GG/CC, GT/CT, TT/TT, GA/CC, and TA/CT). As compared with the 2677GG/3435CC subjects, the AUC(0-24) values were 17% lower in the 2677AA/3435CC subjects and 47% higher in the 2677TT/3435TT subjects (GG/CC versus AA/CC versus TT/TT, 4017 +/- 1137 ng . h/mL versus 3315 +/- 958 ng . h/mL versus 5934 +/- 2,064 ng . h/mL; P=.018). By stratification for genotypes at position 3435, homozygous 3435TT subjects were found to have significantly higher AUC(0-24) (P=.024) and maximum plasma concentration (P=.040) values than CC subjects [AUC(0-24), 5934 +/- 2064 ng . h/mL versus 3998 +/- 1241 ng . h/mL; maximum plasma concentration, 958 +/- 408 ng/mL versus 673 +/- 242 ng/mL]. CONCLUSIONS: The plasma concentrations of fexofenadine after a single oral administration were lower in 2677AA/3435CC subjects than in subjects with the other 5 genotype combinations of the SNPs of G2677T/A and C3435T. These findings confirm the importance of analyzing MDR1 haplotypes and provide a plausible explanation for the conflicting results regarding the effect of MDR1 polymorphisms on the disposition of P-gp substrates.     

Normal Range of the Inflammation Related Laboratory Findings and Predictors of the Postoperative Infection in Spinal Posterior Fusion Surgery

Background

Inflammation related hematological parameters vary greatly depending on patients. It is not well known how much increase of which parameter warrants suspicion of postoperative infection. This study proposes to identify the normal range and the predictive factors for postoperative infection by conducting a time series analysis of the hematological parameters of patients after the spinal posterior fusion.

Methods

A retrospective study was done with 608 patients who underwent spinal posterior fusion with pedicle screw fixation. Laboratory assessment including the leucocyte, neutrophil, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) of patients for 2 weeks after operation. The patients were divided into the one-level fusion group (group I), the two-level fusion group (group II), the three or multi-level fusion or reoperation group (group III), and the postoperative infection group (group IV). Blood was drawn before breakfast prior to the operation, and then 2-3 days, 4-7 days, 8-11 days, and 12-14 days after the operation. The leucocyte count, neutrophil count, CRP, and ESR were measured.

Results

From 4-7 days after the operation, the CRP and neutrophil count of group IV were significantly higher than those of group I and II, and from 8-11 days after operation, the CRP and neutrophil counts were significantly higher than those of all groups. Twelve to fourteen days after the operation, the neutrophil count of group IV was significantly higher than that of group I and II, while the neutrophil count of group III was also higher than that of group I. The lower limit of the 95% confidence interval (CI) of the CRP and neutrophil count group IV was greater than the upper limit of the 95% CI of group I and II. The ESR of group IV was significantly higher than that of group I and III.

Conclusions

If the postoperative CRP and neutrophil counts are high, or if the CRP begins to rise again 8 days after the operation, the likelihood of infection increases, but caution must be exercised in interpreting the results. If the hematological parameters are higher than the lower limit of the 95% CI of the postoperative infection group, infection must be strongly suspected.     

Pharmacokinetic Interactions Between Eperisone Hydrochloride and Aceclofenac: A Randomized,Open-Label,Crossover Study of Healthy Korean Men

Background

Eperisone hydrochloride, a centrally acting muscle relaxant, is a calcium antagonist that causes vasodilation and antispastic actions. Aceclofenac, an anti-inflammatory analgesic and antipyretic drug, has similar efficacy and improved gastrointestinal tolerance compared with other nonsteroidal anti-inflammatory drugs, such as diclofenac. Although eperisone hydrochloride and aceclofenac are frequently coadministered, no published studies have reported on the pharmacokinetic interactions between these 2 drugs.

Objective

The aim of this study was to investigate any pharmacokinetic interactions between eperisone hydrochloride and aceclofenac in healthy Korean men.

Methods

This was a randomized, open-label, crossover study. Each participant was randomly assigned to 1 of 6 treatment sequences and received eperisone hydrochloride (3 doses of 50 mg each), aceclofenac (2 doses of 100 mg each), or both as a single dose with a 7-day washout period between each dose. Blood samples were collected ≤24 hours after dosing, and plasma eperisone hydrochloride and aceclofenac concentrations were determined using validated LC/MS-MS. Pharmacokinetic analyses were conducted using noncompartmental methods. A safety profile was determined using the measurement of vital signs, ECG, and clinical laboratory tests.

Results

A total 24 of men were enrolled, and all completed the study. The geometric mean ratios (90% CIs) of the C_max and AUC_0-∞ values for eperisone were 1.18 (0.828–1.673) and 1.12 (0.836–1.507), respectively. The geometric mean ratios (90% CIs) of the C_max and AUC_0-∞ for aceclofenac were 0.93 (0.847–1.022) and 1.01 (0.979–1.036), respectively. A total of 7 adverse events were reported in 7 men. All adverse events were mild, and no significant differences were found between treatment groups.

Conclusion

No clinically significant pharmacokinetic differences exist between 150 mg eperisone hydrochloride and 200 mg aceclofenac when administrated as a monotherapy or in combination.     

A phase II study of perioperative S-1 combined with weekly docetaxel in patients with locally advanced gastric carcinoma: clinical outcomes and clinicopathological and pharmacogenetic predictors for survival

Gastric Cancer - We conducted a phase II study to evaluate the efficacy and safety of perioperative S-1 plus docetaxel in locally advanced gastric cancer (LAGC) and to investigate the association...