Effects of Acute Experimental Stress on Pain Sensitivity and Cortisol Levels in Healthy Participants: A Randomized Crossover Pilot Study.

AIMS: To investigate pain sensitivity in the masseter muscle and index finger in response to acute psychologic stress in healthy participants. METHODS: Fifteen healthy women (23.7 ± 2.3 years) participated in two randomized sessions: in the experimental stress session, the Paced Auditory Serial Addition Task (PASAT) was used to induce acute stress, and in the control session, a control task was performed. Salivary cortisol, perceived stress levels, electrical and pressure pain thresholds (PTs), and pain tolerance levels (PTLs) were measured at baseline and after each task. Mixed-model analysis was used to test for significant interaction effects between time and session. RESULTS: An interaction effect between time and session occurred for perceived stress levels (P < .001); perceived stress was significantly higher after the experimental task than after the control task (P < .01). No interaction effects occurred for salivary cortisol levels, electrical PTs, or pressure PTLs. Although significant interactions did occur for electrical PTL (P < .05) and pressure PT (P < .001), the simple effects test could not identify significant differences between sessions at any time point. CONCLUSION: The PASAT evoked significant levels of perceived stress; however, pain sensitivity to mechanical or electrical stimuli was not significantly altered in response to the stress task, and the salivary cortisol levels were not altered in response to the PASAT. These results must be interpreted with caution, and more studies with larger study samples are needed to increase the clinical relevant understanding of the pain mechanisms and psychologic stress.

Study on the effect of chemoembolization combined with microwave ablation for the treatment of hepatocellular carcinoma in rats.

PURPOSE: We aimed to evaluate the combining effects of transarterial chemoembolization (TACE) and open local thermal microwave ablation in a hepatocellular carcinoma animal model. METHODS: Tumor cubes were implanted into the liver of 30 male inbred ACI rats. Groups of 10 animals were treated at 13 days (TACE or microwave ablation) and 16 days (microwave ablation) postimplantation with combined therapy of TACE (0.1 mg mitomycin C; 0.1 mg iodized oil; 5.0 mg degradable starch microspheres) and microwave ablation (2450 Mhz; 45 s; 35 W) (study group A), TACE alone (control group B), or microwave ablation alone (control group C). At day 12 and day 25 tumor size was measured via magnetic resonance imaging and the relative growth ratio was calculated. Hepatic specimens were immunohistochemically examined for the expression of vascular endothelial growth factor (VEGF). RESULTS: Mean growth rates were 1.34±0.19 in group A, 3.19±0.13 in group B, and 4.18±0.19 in group C. Compared with control groups B and C, tumor growth rate in group A was significantly inhibited (P < 0.01). The VEGF-antibody reaction in peritumoral tissue (staining intensity at portal triad, percent antibody reaction and staining intensity at central vein) was significantly lower in group A compared with group B (P < 0.01). No significant difference between group A and group C could be observed. CONCLUSION: This investigation shows improved results of TACE followed by microwave ablation as treatment of hepatocellular carcinoma in a rat model, compared with single therapy regimen regarding the inhibition of growth rate and reduction of VEGF-level in peritumoral tissue.

Transarterial administration of integrin inhibitor loaded nanoparticles combined with transarterial chemoembolization for treating hepatocellular carcinoma in a rat model.

AIM: To compare the effect of transarterial chemoembolization (TACE) plus GRGDSP (Gly-Arg-Gly-Asp-Ser-Pro, integrin-inhibitor) loaded nanoparticles with TACE alone or TACE + GRGDSP in a rat model of liver tumor. METHODS: Morris hepatoma 3924A tumors were implanted in the livers of 30 ACI rats. The ACI rats were divided randomly into three groups (10 animals each). Tumor volume before treatment (V1) was examined by magnetic resonance imaging (MRI), and then, after laparotomy and placement of a PE-10 catheter into the hepatic artery, the following interventional protocols were performed: TACE (mitomycin C + lipiodol + degradable starch microspheres) + GRGDSP loaded nanoparticles for group A; TACE + GRGDSP for group B (control group 1); TACE alone for group C (control group 2). Tumor volume (V2) was assessed by MRI and the mean ratio of the post-treatment to pretreatment tumor volumes (V2/V1) was calculated. Immunohistochemical analysis was performed to assess the quantification of matrix metalloprotein 9 (MMP-9) and vascular endothelial growth factor (VEGF) positive tumor cells in each treatment group. RESULTS: The mean tumor growth ratios (V2/V1) were 1.3649 ± 0.1194 in group A, 2.0770 ± 0.1595 in group B, and 3.2148 ± 0.1075 in group C. Compared with groups B and C, group A showed a significant reduction in tumor volume. Lower expression of MMP-9 and VEGF in hepatocellular carcinoma was observed in group A than in groups B and C. The angiogenesis of tumor was evaluated using anti-VEGF antibodies, and the metastasis of tumor was assessed using anti-MMP-9 antibody. MMP-9 and VEGF were expressed in all specimens. The immunoexpression of these proteins was confirmed by the presence of red cytoplasmic staining in tumor cells. Lower expression of MMP-9 and VEGF in hepatocellular carcinoma was observed in group A than in groups B and C. CONCLUSION: Transarterial administration of integrin inhibitor loaded nanoparticles combined with TACE evidently retards tumor growth and intrahepatic metastases compared with TACE alone or TACE plus integrin inhibitor in an animal model of hepatocellular carcinoma.

Transarterial chemoembolization of hepatocellular carcinoma in a rat model: the effect of additional injection of survivin siRNA to the treatment protocol.

BACKGROUND: Transarterial chemoembolization is one of the most widely accepted interventional treatment options for treatment of hepatocellular carcinoma. Still there is a lack of a standard protocol regarding the injected chemotherapeutics. Survivin is an inhibitor of Apoptosis protein that functions to inhibit apoptosis, promote proliferation, and enhance invasion. Survivin is selectively up-regulated in many human tumors. Small interfering RNA (siRNA) can trigger an RNA interference response in mammalian cells and induce strong inhibition of specific gene expression including Survivin. The aim of the study is to assess the effectiveness of the additional injection of Survivin siRNA to the routine protocol of Transarterial Chemoembolization (TACE) for the treatment of hepatocellular carcinoma in a rat model. METHODS: The study was performed on 20 male ACI rats. On day 0 a solid Morris Hepatoma 3924A was subcapsullary implanted in the liver. On day 12 MRI measurement of the initial tumor volume (V1) was performed. TACE was performed on day 13. The rats were divided into 2 groups; Group (A, n = 10) in which 0.1 mg mitomycin, 0.1 ml lipiodol and 5.0 mg degradable starch microspheres were injected in addition 2.5 nmol survivin siRNA were injected. The same agents were injected in Group (B,=10) without Survivin siRNA. MRI was repeated on day 25 to assess the tumor volume (V2). The tumor growth ratio (V2/V1) was calculated. Western blot and immunohistochemical analysis were performed. RESULTS: For group A the mean tumor growth ratio (V2/V1) was 1.1313 +/- 0.1381, and was 3.1911 +/- 0.1393 in group B. A statistically significant difference between both groups was observed regarding the inhibition of tumor growth (P < 0.0001) where Group A showed more inhibition compared to Group B. Similarly immunohistochemical analysis showed significantly lower (p < 0.002) VEGF staining in group A compared to group B. Western Blot analysis showed a similar difference in VEGF expression (P < 0.0001). CONCLUSION: The additional injection of Survivin siRNA to the routine TACE protocol increased the inhibition of the hepatocellular carcinoma growth in a rat animal model compared to regular TACE protocol.

Benefit of piezoosteotomy in cranioplasties for craniosynostosis correction versus conventional saw-and-chisel osteotomy: a pilot study.

OBJECTIVE: Pilot study evaluation of the benefit of piezoosteotomy in cranioplasty of craniosynostoses, based on clinical data. DESIGN: Retrospective case-control study. SETTING: Universitarian institution. PATIENTS: Craniosynostosis patients (n = 19) operated upon conventionally with a craniotome and microsaw versus 19 patients operated upon with a piezoosteotomy and a craniotome. INTERVENTION: Piezoosteotomy of the supraorbital "bandeau" and osteotomies on part of the parietal and occipital regions versus conventional saw-and-chisel osteotomy. MAIN OUTCOME MEASURES: Perioperative age, weight, laboratory parameters, transfusion and infusion requirements, operation time, and blood loss. RESULTS: The intraoperative erythrocyte concentrate transfusion and noncolloidal infusions were comparable (P = .15; P = .56). The fresh frozen plasma transfusion was significantly higher (P = .03); possibly, the anesthesiologist's reaction was secondary to the higher irrigation-fluid accumulation in the aspiration bag during piezoosteotomy. The postoperative erythrocyte concentrate transfusion rate was significantly lower (P = .01) as a result of local hemostasis in piezoosteotomy. The fresh frozen plasma transfusion and noncolloidal infusion volumes were nonsignificantly lower (P = .27; P = .85). Operation time was slightly shorter with a smaller standard deviation (P = .09), due to a lower rate of dural lacerations and consecutive repair; patients in the study group were on the intensive care unit half a day less (P = .73) than those in the control group. C-reactive protein was significantly lower preoperatively (P = .00) and on the operation day (P = .01) and nonsignificant postoperatively (P = .81); hematocrit was postoperatively higher (P = .23). Thrombocytes were preoperatively lower and postoperatively higher, both nonsignificant (P = .29; P = .52). CONCLUSIONS: Piezoosteotomy appears to be less traumatic than conventional saw-and-chisel osteotomy by the evaluated parameters. The main study limitation is its nonrandomized retrospective design; results should be confirmed by a randomized controlled trial.

Treatment of malar and midfacial fractures with osteoconductive forged unsintered hydroxyapatite and poly-L-lactide composite internal fixation devices.

PURPOSE: To evaluate the internal fixation of malar and midfacial fractures, long-term results, and biocompatibility of osteoconductive internal fixation devices composed of a forged composite of unsintered hydroxyapatite and poly-L-lactide (F-u-HA/PLLA). MATERIALS AND METHODS: From January 2006 to June 2010, 29 patients (24 males and 5 females; age 33 ± 15 years) were included in the present prospective study. The fracture type was malar in 24 patients, midfacial in 5, isolated orbital floor blowout in 2, and frontal sinus, cranial base in 2 patients. The fractures were fixed with internal fixation devices; these were plates and screws composed of F-u-HA/PLLA. The 24 patients with malar fractures were treated with a single 4-hole L-plate or a straight plate at the infrazygomatic crest. RESULTS: All fractures with internal fixation using devices composed of F-u-HA/PLLA healed well. All malar and midfacial fractures had satisfactory long-term stability. The follow-up examinations at 12 to 67 months after surgery showed that most patients had no complaints, although 2 patients (15%) had a foreign body reaction that was treated by implant removal, with complete symptom resolution. At 5 years after fracture fixation, 2 patients had ultrasound and 2 had radiographic evidence of residual material. An exemplar biopsy showed direct bone growth into the material. CONCLUSIONS: In patients with malar and midfacial fractures, hardware composed of the F-u-HA/PLLA composite provided reliable and satisfactory internal fixation, intraoperative handling, long-term stability, and biocompatibility. Direct bone growth into the material could be histopathologically exemplified, in contrast to previous polymer fixations that were resorbed and surrounded by a connective tissue layer. This finding indicates that long-term F-u-HA/PLLA residual material will be included into the remodeled bone, which was confirmed on long-term follow-up radiographs.

Low to high oblique ramus piezoosteotomy: a pilot study.

Two major drawbacks of classical bilateral sagittal split osteotomy (BSSO) are occasional inferior alveolar nerve damage and bad splits. In order to avoid these two well-known disadvantages and benefit from ultrasonic bone cutting, a low-to-high oblique piezoosteotomy (LHO) was developed from Schlössmann's 1922 high oblique osteotomy, clinically evaluated with a standard and a novel osteosynthesis system. Eighty-five patients were retrospectively evaluated, 23 with an LHO osteotomy with standard osteosynthesis, 33 LHO with a dedicated plate osteosynthesis and compared to 29 patients with BSSO and standard osteosyntheses. The mean mandibular advancement in the LHO standard osteosynthesis/LHO dedicated plate osteosynthesis/BSSO collectives was 4.7 ± 2.5/7.8 ± 7.1/4.1 ± 2.8 mm, the mean one year relapse 2.6 ± 0.8 (p = 0.58)/1.4 ± 1.4 (p = 0.28)/2.1 ± 1.4 mm; the mean mandibular setback was 6.9 ± 3.6/7.7 ± 4.1/8.1 ± 4.9 mm and the one year relapse 2.9 ± 2.9 (p = 0.16)/1.4 ± 1.0 (p = 0.38)/1.5 ± 1.9 mm; clockwise rotation of the mandible was 5.2 ± 3.2/6.3 ± 5.1/10.2 ± 6.9°, the one year relapse 2.7 ± 1.2 (p = 0.18)/2.1 ± 1.7 (p = 0.09)/11.4 ± 9.3°; counterclockwise rotation averaged 6.4 ± 3.2/6.5 ± 7.9/6.5 ± 6.1° with a mean one year relapse of 3.3 ± 0.6 (p = 0.37)/3.7 ± 1.9 (p = 0.21)/4.5 ± 6.2°. LHO had 3%, BSSO 5% three months postoperative inferior alveolar nerve deficit (p = 0.17). The operation time was significantly shorter when LHO and dedicated plates were used compared to BSSO. Two broken conventional plates occurred in LHO, which stimulated the development of the dedicated plates used, one in BSSO; four bad splits in BSSO and two in LHO. Reosteosyntheses were performed using the newly developed dedicated "orthognathics" plate. LHO was successfully performed, easier and faster than BSSO. Gonial angle modifications were possible due to the oblique cut. Postoperative stability appears sufficient for moderate repositioning with a lower incidence of bad split and inferior alveolar nerve irritation, moreover blood loss was reduced. Since 2 standard miniplate fractures occurred in LHO, the "orthognathics" osteosynthesis was developed, applied and no further osteosynthesis fractures were seen.

Segmental stability in orthognathic surgery: hydroxyapatite/Poly-l-lactide osteoconductive composite versus titanium miniplate osteosyntheses.

Hydroxyapatite was included into F-u-HA/PLLA (unsintered hydroxyapatite - Poly l-lactide) composite osteosynthesis material for its documented osteoconductive capacity. This study investigates segmental retention capacities and outcome stability using F-u-HA/PLLA composite osteosyntheses in orthognathic surgery. Of fifty patients in total, 25 patients were osteofixated with F-u-HA/PLLA osteoconductive bioabsorbable osteosyntheses and compared to a group of 25 patients treated with titanium miniplates. The F-u-HA/PLLA group included 14 maxillary advancements, 4 setbacks, 13 impactions, 5 elongations at A-point; the titanium group included 20 maxillary advancements, 2 setbacks, 11 impactions and 11 elongations. In the mandible the F-u-HA/PLLA group included 13 advancements at B-point, 11 setbacks, 16 clockwise rotations and 8 counterclockwise rotations at the Gonial angle (Ar-Go-Gn); the titanium group included 9 mandibular advancements, 5 setbacks, 8 clockwise rotations and 6 counterclockwise rotations at Ar-Go-Gn. Segmental stability and relapse were assessed comparing preoperative, postoperative and follow-up roentgen cephalometrics at 22 ± 11 months on average in F-u-HA/PLLA cases, 24 ± 22 months on average in the titanium group. All absolute operative movements were nonsignificant in the F-u-HA/PLLA cases compared to the titanium osteosynthesis cases. Relapses were nonsignificant but there was greater vertical relapse in maxillary impactions with titanium osteosyntheses. Throughout this study, F-u-HA/PLLA composite osteosyntheses appeared as stable as titanium miniplates. It can therefore be concluded, although from a limited number of patients, that the investigated osteoconductive osteosynthesis can be used in a similar way to titanium miniplates in orthognathic surgery. Compared to earlier studies using other bioabsorbable polymers in the literature, F-u-HA/PLLA proved to be more stable in segmental retention.

Long-term prospective teaching effectivity of practical skills training and a first OSCE in cranio maxillofacial surgery for dental students.

Basic skills in oral/CMF surgery should be taught effectively to dental students as surgical skills training is traditionally under-represented in the dental curriculum compared to its later need in daily clinical practice. Rigid curricular time frames and prospectively condensed professional education foster new effective teaching and examination formats. Transmitting and assessing clinical competence objectively (independent of subjective bias), reliably (repeatable, inter-rater consistency) and valid (representative, structured task selection) was intended and evaluated in oral/CMF surgery skills acquisition starting in summer 2009. A small-group practical skills training (PST) day initiated a one-week practical training course, covering previously formulated learning objectives. An objective structured clinical evaluation (OSCE) was held at the end of each semester. Theoretical background knowledge and clinical skills should have to be memorized within a representative number of practical tasks (test stations). A first semester (26 students) used classical practical training alone as controls, the following semesters (171 students) had PST, considered as a study group. All 197 students were assessed with OSCE's over a 3-year period. An instructor held PST based on presentations, videos and practical training, including mannequins, with pairs of students. This included history taking, communication and interpretation of laboratory/image diagnostics, structured clinical facial examination, fracture diagnosis, venipuncture, suturing, biopsy and wire loops on pig jaws for manual and clinical skills, which were later incorporated in OSCE stations. OSCE average results increased from 63.3 ± 9.7% before and to 75.5 ± 10% after the inclusion of PST (p < 0.05). Knowledge diffusion between sittings on the same test date and between consecutive semesters was insignificant. Students and faculty rated their learning/teaching experience "very good" to "good". PST was effective in optimizing clinical skills as evaluated by OSCE.