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.

Accumulation of plasma cells expressing CXCR3 in the synovial sublining regions of early rheumatoid arthritis in association with production of Mig/CXCL9 by synovial fibroblasts.

Accumulation of plasma cells in the synovium is one of the diagnostic hallmarks in the histopathological manifestations of rheumatoid arthritis (RA). This seems to be prominent even prior to significant B cell infiltration and/or formation of lymphoid follicles in the synovium. To clarify the mechanism of early plasma cell accumulation, we examined in situ expression of chemokines and their receptors using synovial targeting biopsy specimens, which were obtained under arthroscopy from early RA patients. By immunohistochemical staining, plasma cells were found to express a chemokine receptor CXCR3, while synovial fibroblasts in the synovial sublining regions expressed its ligand, Mig/CXCL9. By reverse transcription-polymerase chain reaction (RT-PCR), using targeted lesions of synovial tissues obtained by laser capture microdissection, expression levels of Mig/CXCL9 in the synovial sublining regions were remarkably high and were likely to be associated with interferon (IFN)-gamma expression. Furthermore, cultured synovial fibroblasts were confirmed to produce Mig/CXCL9 upon stimulation with IFN-gamma. Our results indicate that in the early stage of RA, plasma cells expressing CXCR3 may be recruited directly from the circulation into the synovial sublining regions by its ligand, Mig/CXCL9, produced by synovial fibroblasts.

Localization of sex steroid receptor cells, with special reference to thymulin (FTS)-producing cells in female rat thymus.

Using monoclonal antibodies against progestin receptors (PR) and estrogen receptors (ER), and polyclonal antibodies to thymulin (FTS) and keratin, localization of the sex steroid receptors was studied immunohistochemically in ovariectomized estrogen-treated rat thymus, with special reference to FTS-producing cells. Both ER- and PR-immunostained cells were mainly localized in the medullary region, especially at its periphery (i.e., the corticomedullary junction). A few cells were also situated in the subcapsular area. They were medium- to large-sized and had a dendritic cell process, some of which were immunohistochemically keratin- and FTS-positive, indicative of reticuloepithelial (RE) cells. Hassall's corpuscles were also receptor-positive and FTS-positive. T-cells were not immunostained with anti-ER, anti-PR or anti-FTS. Light microscopically, both ER and PR immunostainings were localized in the cytoplasm and/or nucleus of keratin-stained RE cells. Electron microscopically, both steroid receptors were shown more precisely to distribute as aggregates of osmiophilic black dots on polysomes and perinuclear space in the cytoplasm and on the euchromatin area in the nucleus. These results suggest that the sex steroids E and P exert their effects through receptors within RE cells which produce FTS to regulate T-cell differentiation.

Hormone and immune response, with special reference to steroid hormone. 2. Sex steroid receptors in rat thymus.

In this study, we characterized the sex hormone receptors in normal and abnormal rat thymus tissues using biochemical and immunohistochemical techniques. Judging from the experimental results, the progestin and the estrogen receptor-containing cells and the thymulin-producing cells are the same reticuloepithelial (RE) cells. This suggests that the sex steroids mediate immune functions of the thymus through receptors within the RE cells to produce thymulin which induces the thymocyte to differentiate and mature. Whether the sex hormones have any direct effects on either T or B cells is not known at this time. So, further studies are needed to clarify this point. Secondly, using the spontaneously developed thymoma tissues from BUF/Mna rat the present authors have just started to biochemically analyse the existence of sex hormone receptors and to immuno-histochemically identify sex hormone receptor-containing cells and thymulin-producing cells. As a contemporary result, progesterone and estrogen receptors were mainly located in the intact RE cells but not in the neoplastic cells, whereas thymulin-producing cells were in both intact RE cells and neoplastic cells. It seems by now that there is no correlation between steroid hormone receptors and thymulin production in the neoplastic cells, as would be in the intact RE cells. Further study is required to answer this question.

Hormone and immune response, with special reference to steroid hormone 1. A short review.

Substantial evidence has been accumulated to support the gonadal regulation of immune functions. They are mainly based on the following observations: i) the existence of sexual dimorphism in immune response, ii) alteration of immune response by gonadectomy or sex steroid replacement, iii) alteration of immune response during pregnancy, and iv) existence of sex steroid receptors in the thymus tissue which affect T cell function through thymic hormones produced in the gland. In the present study, we have tried to review some of this evidence by adding our own findings. We also referred to the experimental findings which show that the thymus, brain and gonads are close-related functionally, and form a functional axis, the so-called "hypothalamic-pituitary-gonadal-thymic" axis which is of great importance not only because it regulates immune response, but because its influence may extend to other organ system within the living body.

Hormone and immune response, with special reference to steroid hormone. 3. Sex steroid effect on T-cell differentiation.

Effect of sex steroids on differentiation of mouse thymic lymphocytes (T cells) was investigated. The result obtained are as follows: (i) the receptors for estrogen and progestin are both in the thymic cytosol, and they are mainly located in the reticuloepithelial cells in which thymulin (FTS) is also localized, (ii) estrogen and thymulin affect thymic weight and T cell differentiation, especially helper T cell subset, and (iii) estrogen may play a role through its receptor on thymic reticuloepithelial cells to produce thymulin which in turn influences T cell function.

Nuclear progestin receptors in rat thymic tissue.

The thymus and its associated endothelial cells and lymphocytes act as an important immunological tissue. The endothelial cells of the thymus have been reported to synthesize cytoplasmic progestin receptor in response to estrogen priming. To measure nuclear progestin receptor, female rats were castrated and primed for 3 days with estradiol benzoate (30 micrograms/0.1 ml/d) and immediately before sacrifice injected subcutaneously with 0.2 mg of progesterone. By Scatchard plot analysis we found that specific progestin receptor (KA = 0.89 +/- 0.10 x 10(9) M-1) was present in the KCl-nuclear extract. The concentration of nuclear progestin receptor was found to be in the range of 312.6 +/- 49 fmole/g tissue (n = 9, 1 hour after progesterone injection) while the nuclear receptor was significantly reduced (approximately 44 fmol/g tissue) in the oil treated controls. This level verges on the limits of sensitivity for this assay. For cytoplasmic progestin receptor the concentration was 3.46 +/- 0.20 pmole/g tissue in oil treated controls (n = 14) and 3.36 +/- 0.20 pmole/g tissue in progesterone treated animals (n = 24). The KA of this thymic cytoplasmic progestin receptor was 1.35 +/- 0.06 x 10(9) M-1. By competition assay, the relative binding affinity of nuclear progestin receptor was: R5020 (a potent synthetic progestin) (100%), progesterone (9%), testosterone (0.56%), corticosterone (0.53%), estradiol-17 beta (0%). It is concluded that thymic reticuloepitheleal cells contain nuclear progestin receptor and this finding supports the hypothesis that progesterone, like other sex steroids may play a regulatory role in thymic cell function.

Hormonal events surrounding spontaneous onset of puberty in female rats.

In an effort to define more completely the hormonal events surrounding onset of puberty in female rats, concentration of sex steroids and gonadotropins in serum, ovaries and pituitaries were quantified. Simultaneously the sites and intensity of synthesis of the hormones were observed immunohistochemically. It was found that an increase in tissue concentration of follicle stimulating hormone (FSH), luteinizing hormone (LH), progeterone (Po) and estradiol (E2) preceded vaginal opening (VO). However, the serum levels of these hormones were not significantly increased until the day of VO except for serum E2 levels which were fairly high during the early prepubertal period. Coincident with an increase in pituitary gonadotropin levels was an increase in the staining intensity for pituitary gonadotropes. However, the increase in ovarian steroid levels was not always coincident with the staining intensity for steroid-producing cells. The site or localization of steroid synthesis in the ovary was the thecal layer, but not the granulosa, of various growing follicles. The present results clearly indicated that the preovulatory changes in gonadotropins and sex steroids in blood and the tissues are similar to those noted in cycling adult rats, suggesting that prepubertal gonadotropin surge is induced via a common mechanism. They also indicated that ovarian steroids, especially estrogens, are synthesized mainly in the thecal layer of growing follicles.

Progestin and estrogen receptors: characterization and localization in rat submandibular glands, with special reference to epidermal growth factor.

By using progestin (P) and estrogen (E), the localization and characterization of both steroid receptors were examined in the submandibular gland (SMG) of 6-week-old immature castrated rats, with special reference to localization of epidermal growth factor (EGF). In the castrated male and female rats, both 3H-estradiol-17 beta (3H-E2 beta) and 3H-promegestone (3H-R5020) bound to SMG cytosol with high affinity and low capacity. These values were similar to those reported for other tissues. However, E-treatment after castration inhibited the specific binding. In sucrose density gradient ultracentrifugation, it was found that P receptors in both castrated males and females had a sedimentation coefficient of 7S, whereas E receptors had sedimentation coefficients of 4S and 7S. A histochemical study of the SMG of castrated male and female rats showed that the E-peroxidase complex (EPC)- and P-peroxidase complex (PPC)-stained cells were predominantly located in the epithelium of the duct system including the excretory duct and the granular convoluted tubules. Few cells were located in the intercalated duct, and none were found in the acinus. EGF-immunoreactive cells were also located in the epithelium of the same tissue region as in PPC- and EPC-stained sections. Moreover, E-treatment after castration inhibited the intensity of staining and immunoreactivity. These results clearly suggest that rat SMG contains specific P and E receptors which are mainly located in the epithelial cells of the duct system in which EGF-containing cells are identified. We discussed the possibility that P and E might affect EGF immunoreactivity, which reflects EGF production, through their receptors in the epithelium of the duct system.

An experimental study on isochronal ventricular mapping in acute myocardial infarction.

Simultaneous epicardial (EP) and endocardial (EN) isochronal mapping during spontaneous ventricular arrhythmia was attempted in a experimental model of acute myocardial infarction. The left anterior descending artery (LAD) was ligated in 12 open-chest mongrel dogs. A total of 86 electrode terminals, 43 for EP and 43 for EN, were inserted over the infarction, border and normal areas, and connected to a computerized data acquisition system. Data for each ventricular arrhythmia were stored on disks for 3 hours following ligation and were analyzed to obtain isochronal EP and EN maps. Finally, the heart was sliced and stained by the TTC technique. In a comparison with TTC staining, the earliest activation sites of ventricular arrhythmias estimated from the isochronal maps 3 hours postligation were located in various areas but localized exclusively in the border zones. Moreover, the earliest activation sites tended to change their locations from EN to EP throughout the time course following ligation. In several spontaneous ventricular arrhythmias, findings suggestive of functional blocks and reentry circuits were also delineated in EP and EN maps.

Biochemical characterization and immunohistochemical localization of progestin and estrogen receptors in castrate rat submandibular gland.

The physicochemical property and immunohistochemical localization of progestin (P) and estrogen (E) receptors (PR and ER) were examined in the submandibular gland (SMG) of 5-8-week-old castrated rats. The localization of epidermal growth factor (EGF) was simultaneously examined in the same tissue. The tissue cytosols from male and female rats specifically bound 3H-promegestone (3H-R5020) and 3H-estradiol-17 beta with high affinity and low capacity; the values were within the range of those reported for other tissues. However, E-treatment suppressed the specific P-binding in the female, whereas it did not in the male. On the contrary, E-treatment did not at all suppress specific E-binding in both sexes. Monoclonal antibodies against PR and ER were mainly located in the epithelium of the excretory duct and granular convoluted tubule, but not in the acinus. The monoclonal antibodies were also located in the large polygonal cell with irregular cell border, probably macrophage in the tissue. The EGF-immunoreactivity was observed in the epithelium of the same tissue region as that in which the monoclonal antibodies were located. The present results clearly suggest that the rat SMG tissue contains specific PR and ER that are mainly located in the epithelium of the duct system where EGF-producing cells are also located. The possibility that P and E may influence EGF-production through their receptors in this tissue was discussed.

Immunohistochemical evidence of progestin target cells in the pituitary gland of ovariectomized rat.

Progestin (P) target cells were identified in the pituitary gland of gonadectomized female rats which had been primed with estrogen (E). P staining was localized using the immunohistochemical avidin-biotin-peroxidase (ABP) complex method. Dark brown precipitates were primarily found over the cytoplasm of cells in the pars distalis, but not in the pars intermedia nor in the pars nervosa. The majority of P-sensitive cells in the pars distalis were identical with luteotrophs, a few being lactotrophs. These observations suggest a role of P in the regulation of production and secretion of gonadotrophins in the pituitary glands of female rats.

Histochemical localization of progestin receptor cells in the rat thymus.

Using progesterone (Po)-horseradish peroxidase (HRP) conjugate (PPC), the histochemical localization of progestin (Pi) receptor in the female rat thymus was investigated. The PPC staining was predominantly detected in the large polygonal cells with irregular cell borders that contain large clear, round or oval nuclei, 'epithelial cells', but rarely in the small round cells with dark round or oval nuclei, 'thymic lymphocytes'. The PPC-positive cells were distributed everywhere in the tissue, but found more frequently at the corticomedullary junctional area than at the other tissue areas. The stained cells tended to gather to make a cell cluster. The PPC staining within the epithelial cells was predominantly localized in the cytoplasm, but only faintly in the nucleus. The steroid specificity of Pi binding was studied by simultaneous incubation of the tissue sections with PPC and a series of unconjugated steroids such as progesterone-3-O-carboxymethyl oxime (PCMO), progesterone (Po), testosterone (T), estradiol-17 beta (E2 beta) and corticosterone (CC). The incubation studies indicated that two progestins, PCMO and Po, bind to Pi receptor in the thymus with a reasonable degree of specificity, but other nonprogestational steroids do not. The method was reproducible and showed satisfactory technical stability. The present results suggest that the effect of Pi on the thymus may be mediated by Pi receptor present in the epithelial cells.

Progestin receptor in the thymus of ovariectomized immature rats.

By using the synthetic progestin promegestone (R5020), the location and characteristics of progestin receptors in the thymic cytosols from immature ovariectomized oestrogen-treated rats were determined. Tritiated promegestone bound to the cytosol with high affinity (dissociation constant (Kd) = 2.0 +/- 0.3 nmol/l; promegestone greater than progesterone greater than oestradiol greater than corticosterone testosterone) and low capacity (number of binding sites (Bmax) = 143.0 +/- 13.5 fmol/mg protein). These values were appropriate for progestin receptors. However, an extremely high dose of dexamethasone (10 mumol/l; 1000-fold excess over [3H]promegestone) slightly inhibited the specific binding. Progestin receptors were predominantly located in the reticuloepithelial (RE)-cell fraction, with few in the thymocyte T-cell fraction. The receptor level was raised (24.9 +/- 11.3 (S.E.M.) to 143.0 +/- 13.5 fmol/mg protein) with increased doses of oestrogen (0-30 micrograms) administered in vivo. Using sucrose density gradient ultracentrifugation it was found that the thymic progestin receptor had a sedimentation coefficient of 9S under low-salt conditions. These results clearly suggest that the thymus of the immature female rat contains a specific progestin receptor which is mainly located in the RE cells.

Progestin receptors in adult rat ovary during estrous cycle.

Using a synthetic progestin (P)(i.e. R5020), characteristics of P receptors were determined in the ovarian tissue cytosols from adult estradiol benzoate-treated or 4-day cycling rats. In the estradiol benzoate-treated rats a specific 3H-R5020 binding in the cytosol was found with a number of binding sites, V max = 110 fmol/mg protein and the equilibrium dissociation constant, Kd = 14 nM. In the 4-day cycling rats, specific binding was found in the 6-7 S region with the Vmax which fluctuated during the estrous cycle: the sequence of Vmax (fmol/mg protein) was 395 (proestrus) greater than 122 (diestrus) greater than 96 (late estrus) greater than 62 (metestrus) greater than 40 (early estrus). The Kd value varied during the cycle, the highest (22 nM) in proestrus and the lowest (5 nM) in early estrus. In addition, 3H-R5020 binders were thermolabile and of protein in nature. These results suggest that the rat ovary contains P receptors in its cytoplasm with high affinity and low capacity of P binding, the level of which fluctuates during the estrous cycle.