Premedication with midazolam in intellectually disabled dental patients: intramuscular or oral administration? A retrospective study.

BACKGROUND: The use of midazolam for dental care in patients with intellectual disability is poorly documented. The purpose of this study was to determine which method of premedication is more effective for these patients, 0.15 mg/kg of intramuscular midazolam or 0.3 mg/kg of oral midazolam. MATERIAL AND METHODS: This study was designed and implemented as a non-randomized retrospective study. The study population was composed of patients with intellectual disability who required dental treatment under ambulatory general anesthesia from August 2009 through April 2013. Patients were administered 0.15 mg/kg of midazolam intramuscularly (Group IM) or 0.3 mg/kg orally (Group PO). The predictor variable was the method of midazolam administration. The outcome variables measured were Observer's Assessment of Alertness/ Sedation (OAA/S) Scale scores, the level of cooperation when entering the operation room and for venous cannulation, post-anesthetic agitation and recovery time. RESULTS: Midazolam was administered intramuscularly in 23 patients and orally in 21 patients. More patients were successfully sedated with no resistance behavior during venous cannulation in Group PO than in Group IM (p=0.034). There were no differences in demographic data and other variables between the groups. CONCLUSIONS: The results of this study suggest that oral premedication with 0.3 mg/kg of midazolam is more effective than 0.15 mg/kg of midazolam administered intramuscularly, in terms of patient resistance to venous cannulation. If both oral and intramuscular routes of midazolam are acceptable in intellectually disabled patients, the oral route is recommended.

Both head extension and mouth opening impair the ability to swallow in the supine position.

Head position and mouth opening in the supine position may impair the ability to swallow. If this does occur, it would lead to retention of intra-oral fluids during dental treatment, which would lead to stimulation of the cough reflex. This study was conducted to investigate how head position and mouth opening affect swallowing ability. The water swallowing test was performed in 13 healthy adult subjects in the supine position. The subjects were asked to swallow 10 mL of water that was injected into the mouth in a single attempt. After swallowing, the residual intra-oral water was suctioned and its volume was measured. An electromyogram (EMG) of the suprahyoid (SH) muscles was also recorded during the test. The duration of SH muscle activity and peak amplitude of SH EMG were examined. The water swallowing test was performed under three head positions (neutral, extended and flexed) and four mouth opening patterns (interincisal distances of 0, 20, 30 and 40 mm). The wider the subject opened the mouth, the more the water remained in the mouth after swallowing. The residual volume of water was more in the extended position compared with that in the neutral and flexed positions. Peak amplitude of SH EMG decreased with mouth opening. Duration of SH muscle activity was longer in the extended position than in the neutral and flexed positions. Head extension and mouth opening can induce difficulty in swallowing in the supine position by extending the duration of SH muscle activity while reducing its intensity.

IFPA Meeting 2012 Workshop Report III: trophoblast deportation, gestational trophoblastic disease, placental insufficiency and fetal growth restriction, trophoblast over-invasion and accreta-related pathologies, placental thrombosis and fibrinolysis.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2012 there were twelve themed workshops, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of clinical research and pregnancy disorders: 1) trophoblast deportation; 2) gestational trophoblastic disease; 3) placental insufficiency and fetal growth restriction; 4) trophoblast overinvasion and accreta-related pathologies; 5) placental thrombosis and fibrinolysis.

Mapping of a disease susceptibility locus in chromosome 6p in Japanese patients with ulcerative colitis.

Ulcerative colitis (UC) is a multifactorial disorder with both genetic and environmental factors. HLA-B*52 and DRB1*1502 are reported to be strongly associated with UC in Japan. However, the actual susceptible gene has not been identified yet. In this study, to map precisely the susceptible locus for UC, we performed association mapping in the chromosome 6p using 24 microsatellite markers distributed over 16 Mb. A total of 183 patients with UC and 186 healthy controls (HC) were included in this study. In all, 15 markers around the human leukocyte antigen (HLA) region showed statistical significance in the genotypic differentiation test concerned with the allelic distribution between the UC and HC. Especially, the markers between the centromeric region of HLA class I and the telomeric region of class III showed remarkably low P-values and the allele239 of C2-4-4 in class I marker showed the strongest association (Pc=2.9 x 10(-9): OR=3.74, 95% CI=2.50-5.60). Furthermore, we found strong linkage disequilibrium (LD) between the allele239 of C2-4-4 and HLA-B*52 in haplotype analysis. These results provide evidence that, in Japanese, important determinants of disease susceptibility to UC may exist in HLA, especially between the centromeric region of class I and the telomeric region of class III, under the strong LD with HLA-B*52.

Primary tumour resection of tongue carcinoma based on response to preoperative therapy.

The purpose of this study was to investigate the selection of resection techniques for primary lesions of advanced tongue carcinoma based on the effectiveness of our current preoperative therapy. Forty-three patients with advanced but potentially resectable squamous cell carcinoma of the tongue were included in this study. All patients were treated with preoperative concurrent chemoradiotherapy followed by conventional surgical resection. Semiserial sections of whole surgical specimen of primary lesion were evaluated histopathologically. In patients who achieved 85% and above regression, the extent of residual tumours two-dimensionally and in the deep layers was lesser, and the rate of tumour cell survival was lower, than in other patients. Furthermore, residual tumours tended to be localized to the superficial layers in the centre. These findings suggest that even in advanced tongue carcinomas it is possible to avoid extended resection and perform a less invasive surgery in which the extent of resection is reduced to preserve morphology and function in patients who achieved 65% and above regression following preoperative chemoradiotherapy.

Mandibular reconstruction using a vascularised fibula osteocutaneous flap in a patient with pyknodysostosis.

We present the first successful report of mandibular reconstruction using a free fibula osteocutaneous flap in a patient with pyknodysostosis. The patient had recurrent refractory osteomyelitis of the mandible, which was initially treated with resection and reconstruction using an AO plate. Recurrent fistula formation with loosening of the plate was treated by radical re-excision and reconstruction with a free fibula flap. The postoperative course was uneventful; at 14 months the bony union was almost complete, without resorption or atrophy of the grafted fibula on radiography.

Cardiovascular response to epinephrine-containing local anesthesia in patients with cardiovascular disease.

OBJECTIVE: The purpose of the present study was to examine the safety of epinephrine-containing local anesthesia for use on patients with cardiovascular disease. STUDY DESIGN: Twenty-seven patients with cardiovascular disease were studied. The cardiac functional capacity of 9 patients was New York Heart Association class I; 11, class II; and 7, class III. Hemodynamic responses to intraoral injection of 1.8 mL of 2% lidocaine with 1:80,000 epinephrine were measured with impedance cardiography. RESULTS: Systolic blood pressure and heart rate increased by 4.1% and 5.1%, respectively, immediately after the lidocaine-epinephrine injection. Consequently, rate pressure product increased by 10.0%. Cardiac index increased by 14.2%, and total peripheral resistance decreased by approximately 10%. No patient complained of cardiac symptoms. There were no significant differences in hemodynamic responses related to the extent of the cardiac functional capacity. CONCLUSION: We concluded that lidocaine-epinephrine was safe and had few, if any, hemodynamic consequences in patients with cardiovascular disease.

A comparative evaluation of osteosynthesis with lag screws, miniplates, or Kirschner wires for mandibular condylar process fractures.

PURPOSE: This study compared the clinical and radiologic outcomes of open treatment of mandibular condylar process fractures using lag screws, miniplates, or Kirschner wires. PATIENTS AND METHODS: Open reduction and internal fixation was performed for severely displaced or dislocated mandibular condylar process fractures in 23 patients (26 fractures) using Eckelt lag screws, in 10 patients (10 fractures) using Kirschner wires, and in 21 patients (22 fractures) using miniplates. Clinical and radiologic evaluations were made 6 months postoperatively and at final follow-up (mean, 18.4 months; range, 7 to 106 months). Radiologic evaluation included accuracy of reduction of the fractured condylar processes and changes in ramus height. RESULTS: Most fractured condylar processes (approximately 90%) were repositioned precisely in all groups. A shortening of the ramus of more than 5 mm was observed significantly more frequently (P <.05) in the miniplate group than in the lag screw group at 6 months. The condyles were severely resorbed in 2 or 3 patients in each group. All of these patients were associated with malunion, and partial bone resorption of the condyles was seen during the first 6 months. The relation between reduction or screw position and bone healing in patients treated with lag screws indicated that correct reduction and screw insertion allowed normal bone healing. The patients in all groups showed satisfactory clinical results. No significant intergroup differences were noted in maximum mouth opening and laterotrusion. However, deviation during mouth opening was significantly greater (P <.05) in cases treated with miniplates than with lag screws. CONCLUSION: Lag screw osteosynthesis may be more advantageous for restoration of ramus height than miniplates or Kirschner wires.

Synthesis of diaminobutane derivatives as potent Ca(2+)-permeable AMPA receptor antagonists.

We synthesized diaminobutane derivatives as potent Ca(2+)-permeable AMPA receptor antagonists with non-hypotensive activity. Compound 10c showed selective Ca(2+)-permeable AMPA receptor antagonist activity and neuroprotective effects in transient global ischemia models in gerbils.

Changes in masticatory muscle activity according to food size in experimental human mastication.

The purpose of this study was to investigate the changes in masticatory muscle activity according to food size in human mastication. Sixteen subjects performed deliberate unilateral chewing of similarly cone shaped hard gummy jellies weighing 5 and 10 g. The masseter and anterior temporal muscle activity on both sides was recorded for the first 10 strokes. The normalized muscle activity during the chewing of the 10 g jelly was significantly higher than that of the 5-g jelly, and there was a considerably high significant correlationship between the muscle activity during the chewing of the 10- and 5-g jellies in each muscle on each side. The 10 g/5 g jelly ratio for the masseter muscle activity on the non-chewing side almost coincided with the theoretical energy ratio required to shear, although that of the chewing side was lower than the ratio. The 10 g/5 g jelly ratio for the temporal muscle activity on both sides almost coincided with the food height ratio. The results suggest that anterior temporal and masseter muscle activity changes according to the rate of change in the height of hard coherent food bolus and food resistance required to shear, respectively, during mastication.

Effects of volatile and intravenous anesthetics on the uptake of GABA, glutamate and dopamine by their transporters heterologously expressed in COS cells and in rat brain synaptosomes.

Although the neurotransmitter uptake system is considered a possible target for the presynaptic action of anesthetic agents, observations are inconsistent concerning effects on the transporter and their clinical relevance. The present study examined the effects of volatile and intravenous anesthetics on the uptake of GABA, glutamate and dopamine in COS cells heterologously expressing the transporters for these neurotransmitters and in the rat brain synaptosomes. Halothane and isoflurane, but not thiamylal or thiopental, significantly inhibited uptake by COS cell systems of GABA, dopamine and glutamic acid in a concentration-dependent manner within clinically relevant ranges for anesthesia induced by these agents. Similarly, in synaptosomes halothane and isoflurane but not thiopental significantly suppressed the uptake of GABA and glutamic acid, respectively. These results do not support the hypothesis that volatile and intravenous anesthetics exert their action via specific inhibition of GABA uptake to enhance inhibitory GABAergic neuronal activity. Rather, they suggest that presynaptic uptake systems for various neurotransmitters including GABA may be the molecular targets for volatile anesthetic agents.

Intraplacental coagulation in intrauterine growth restriction: cause or result?

Growth-restricted fetuses with complications of pregnancy exhibit significantly increased perinatal morbidity and mortality compared with normal growth fetuses. Coagulation-related lesions such as uteroplacental vessel thrombosis and perivillous coagulation in the placentas with intrauterine growth restriction (IUGR) are reported in complicated pregnancy, while fibrin depositions and intervillous thrombi are observed in half of the placentas of full-term uncomplicated pregnancy. These observations raise the question whether coagulation in the placental circulation is a cause for the development of IUGR. Recently published IUGR models in animals demonstrate that antiphospholipid antibodies and procoagulant platelet-derived phospholipids induce IUGR with histopathological changes of coagulation-related lesions in the placenta. These experiments suggest that enhanced coagulation in the placental circulation can induce IUGR and that hypercoagulable states remain one of the important factors in the development of IUGR.

Predictive values of coagulation/fibrinolysis parameters for the termination of pregnancy complicated by severe preeclampsia.

We investigated coagulation/fibrinolysis parameters for significant differences between patients with early-onset severe preeclampsia (< 32 weeks gestation, wG) and those with late-onset severe preeclampsia (> or = 32 wG). A decrease in antithrombin (AT), protein C (PC), and free protein S (PS) activities and an increase in plasmin-alpha2-plasmin inhibitor complex (PIC), thrombin-antithrombin complex (TAT), and FDP D-dimer (D-dimer) were observed. However, there were no statistical differences between the two groups. Once preeclampsia occurred and it developed severe, the changes in coagulation/fibrinolysis parameters became more severe in spite of early-onset preeclampsia or late-onset preeclampsia. We also investigated coagulation/fibrinolysis abnormalities in 101 patients with severe preeclampsia. A significant increase in WBC, RBC, Hb, Ht, TAT, PIC, and D-dimer and a significant decrease in platelet (Plt) counts and AT activity were observed. deltaPlt (the difference between platelet counts in early gestation and before delivery) was -5.0 x 10(4)/microL in cases with severe preeclampsia. Among patients with severe preeclampsia, coagulation/fibrinolysis changes before delivery were typical for patients with cesarean section compared with those with successful vaginal delivery. These facts suggest that an excessive hypercoagulable state is associated with the termination of pregnancy resulting from the aggravation of preeclampsia. From the viewpoint of coagulation/fibrinolysis changes, the termination of pregnancy could be recommended when the levels of parameters exceed the following values; deltaPlt > -6.0 x 10(4) microL, D-dimer > 4 microg/mL, AT activity < 79%, TAT > 26 ng/mL, and PIC > 1.2 microg/mL. Particularly, deltaPlt and D-dimer are useful bedside predictive markers in order to decide the optimal time for the termination of pregnancy in patients with severe preeclampsia.

Activated protein C prevents development of phosphatidylserine-induced intrauterine growth restriction in mice.

We examined the effect of activated protein C (APC) on the development of intrauterine growth restriction (IUGR) in an experimental animal model we established. The IUGR in mice was induced by artificial phosphatidylserine (PS)/phosphatidylcholine (PC) microvesicles that represent procoagulant phospholipids derived from activated platelets. This model represents the placental insufficiency associated with the phospholipid-induced hypercoagulable state in placental circulation. APC prolonged the activated partial thromboplastin time (aPTT) using mouse plasma and dose dependently inhibited thrombin generation in a chromogenic assay in defibrinated plasma of mice. Administration of exogenous APC at concentrations that maximally inhibited thrombin generation in defibrinated plasma prevented a significant reduction in fetal body weight and induced marked histological changes including congestion and fibrin depositions in IUGR mouse placentas. These results suggest that the inhibition of thrombin generation in the placental circulation by APC prevents the development of IUGR that is dependent on coagulation associated with PS/PC from activated platelets.

Motion of the human mandibular condyle during mastication.

It has been reported that loading to the mandible during closing movement makes the condylar path move more in the superior direction than that during the free closing movement. In this study, the hypothesis was tested that the displacement of the condyle on the chewing side is greater in the direction of the mandibular fossa than that on the non-chewing side. Using a six-degrees-of-freedom jaw movement recording system, we recorded condylar motion in 12 healthy adults without TMD, during the chewing of a large hard gummy jelly. The maximum displacements at the condyle on the chewing side from the maximum intercuspation (CO) position were significantly larger in the superior and medial directions at the initial stage and in the posterior direction at all stages (0.5 mm, 0.5 mm, and 0.6 mm, respectively) than those on the non-chewing side (0.0 mm, 0.1 mm, and 0.1 mm, respectively). This suggests that, in healthy adults, the condyles at CO are located in a position such that excessive load is not applied to the temporomandibular joint when there are the aforementioned displacements.

Recombinant human bone morphogenetic protein-2 potentiates the in vivo osteogenic ability of marrow/hydroxyapatite composites.

A composite of marrow mesenchymal stem cells (MSCs) and porous hydroxyapatite (HA) has bone-forming capability. To promote the capability, we added recombinant human bone morphogenetic protein-2 (BMP) to the composite. The bone formation was assessed by rat subcutaneous implantation of 4 different kinds of implants, i.e., HA alone, BMP/HA composites, MSCs/HA composites, and the composites containing BMP (MSCs/BMP/HA). Both HA and the BMP/HA composites did not show bone formation at any time after implantation. The MSCs/HA composites showed moderate bone formation at 4 weeks and extensive bone formation at 8 weeks. The MSCs/BMP/HA composites showed obvious bone formation together with active osteoblasts at 2 weeks and more bone formation at 4 and 8 weeks. The MSCs/BMP/HA composites demonstrated high alkaline phosphatase and osteocalcin expression at both the protein and gene levels. These results indicate that the combination of MSCs, porous HA, and BMP synergistically enhances osteogenic potential and provides a rational basis for their clinical application in bone reconstruction surgery.

Prognostic value of response to preoperative chemoradiotherapy and residual tumor grades in tongue carcinoma.

OBJECTIVE: The purposes of the present study were to analyze our experience with preoperative chemoradiotherapy followed by surgery for advanced tongue carcinoma and to assess the prognostic value of response to preoperative therapy in these tumors. STUDY DESIGN: Between May 1988 and December 1999, a total of 43 patients with advanced but potentially resectable squamous cell carcinoma of the tongue were candidates for this study. A minimum tumor size of 3 cm was required. The mean age was 59.8 years (range, 26-85 years); 13 cases were advanced stage II, 23 cases were stage III, and 7 cases were stage IV. All patients were treated preoperatively with cisplatin- or carboplatin-based chemotherapy in combination with simultaneous irradiation to a target volume of 40 Gy; 2-6 weeks later, they underwent curative surgery. Tumor regression rate, residual tumor grade, and histologic regression grade to the preoperative therapy were analyzed to determine their influence on the prognosis. RESULTS: With a median follow-up of 60.5 months, overall survival rates were 86.0% for all cases, 92.3% for stage II cases, 77.3% for stage III cases, and 100% for stage IV cases. The progression-free survival rates according to tumor regression rate were 33.3% for group 1 (< 50% tumor regression), 66.7% for group 2 (> or = 50% and < 75% regression), 100% for group 3 (> or = 75% and < 100% regression), and 96.0% for group 4 (complete regression). The higher the tumor regression rates, the higher the survival rates. When patients who achieved a regression rate of 75% or higher were compared with those who did not, there was a significant difference in survival (P < .0001). The factors of residual tumor grade and histologic regression grade also had good correlations with the prognosis (residual tumor grade, P =.0324; histologic regression grade, P < .0001). CONCLUSIONS: The findings of the present study suggest that response to preoperative chemoradiotherapy, such as tumor regression rate, residual tumor grade, and histologic regression grade, could be of prognostic value in patients with tongue carcinoma.

Increased expression of cyclooxygenase-2 protein in 4-nitroquinoline-1-oxide-induced rat tongue carcinomas and chemopreventive efficacy of a specific inhibitor, nimesulide.

Expression of cyclooxygenase (COX)-2 protein in 4-nitroquinoline-1-oxide (4-NQO)-induced rat tongue lesions and the postinitiation chemopreventive potential of a selective COX-2 inhibitor, nimesulide (NIM), were examined in Fischer 344 male rats. NIM was administered in the diet at doses of 150, 300, and 600 ppm for 14 weeks after treatment with 25-35 ppm 4-NQO in the drinking water for 12 weeks. Western blot analysis revealed COX-2 protein to be barely expressed in the normal tongue epithelia, whereas it was increased approximately 6-fold in squamous cell carcinomas (SCCs). Immunohistochemically, COX-2 protein was diffusely present in SCCs and dysplasia but expressed only in basal cells in hyperplasia and papillomas. In basal cells of normal epithelia, it was also occasionally weakly stained. NIM dose-dependently decreased at doses of 150 and 300 ppm, the incidences of SCCs to 4 of 12 (33.3%) and 1 of 13 (7.7%) and their multiplicity to 0.33+/-0.49 and 0.08+/-0.28 per rat, respectively, as compared with 4-NQO alone group values of 9 of 11 (81.8%) and 1.00+/-0.77. A lesser decrease was observed with 600 ppm, the values being 5 of 12 (41.7%) and 0.50+/-0.67. NIM did not significantly affect the development of hyperplasias, dysplasias, and papillomas. These results clearly indicate chemopreventive potential of a selective COX-2 inhibitor against the postinitiation development of SCCs in rat tongue carcinogenesis.

Selective transport of the mulberry leaf urease from the midgut into the larval hemolymph of the silkworm, Bombyx mori.

Just before spinning, larvae of the silkworm, Bombyx mori, absorb intact urease of the host plant (mulberry leaf) from the midgut lumen into the hemolymph. In order to investigate whether the transport of the mulberry leaf urease is selective, crude proteins extracted from the mulberry leaves were labeled with biotin and orally administered to the fifth instar larvae. The biotinylated proteins transported into the hemolymph were detected by ligand blotting using streptavidin. When the biotinylated proteins were administered to 5-day-old fifth instar larvae, a strong signal of a biotinylated protein was detected in the hemolymph 2 days after the administration. In contrast, when the biotinylated mulberry leaf proteins were administered to 3-day-old fifth instar larvae, no signal derived from the biotinylated proteins was detected in the hemolymph. The signal weakened when the biotinylated proteins had been immunoprecipitated before administering to the larvae, indicating that the signal came from the mulberry leaf urease. These results show that the transport of the mulberry leaf urease from the midgut into the hemolymph is selective and larval-stage specific. Subsequently, binding assays were carried out to test the binding ability of the mulberry leaf urease to the brush border membrane in the epithelial cells of larval midgut. The urease was not bound to the brush border membrane vesicles (BBMV) from the midgut of 3-day-old fifth instar larvae, while more than 60% of the total amount of incubated urease was bound to the BBMV from the midgut of 6-day-old fifth instar larvae. The urease binding ability of BBMV correlated with the uptake of the mulberry leaf urease. This suggests that a urease binding molecule(s) exists in the BBM of the midgut epithelium, which is involved in the uptake of the mulberry leaf urease. In addition, the uptake of the mulberry leaf urease into the hemolymph was induced by 20-hydroxyecdysone.