[A clinical application study of digital manufacturing simple intraoral Gothic arch-tracing device in determining the centric relation of complete dentures].

OBJECTIVE: To verify the consistency between the digital manufacturing simple intraoral Gothic arch-tracing device and the traditional intraoral Gothic arch-tracing device in determining the centric relation of complete dentures restoration. METHODS: Ten outpatients with edentulous jaws were selec-ted, and the centric relation of the patients was determined by digital manufacturing of simple intraoral Gothic arch-tracing device (T1) and traditional intraoral Gothic arch-tracing device (T2); the difference of clinical operation time between the two methods was recorded; the upper and lower edentulous jaw plaster models were scanned with two kinds of centric relation, the Standard Triangle Language (STL) files imported into Geomagic studio software to apply the best fitting of multiple points of the both upper jaw models, the fitted STL files imported into the 3 shape viewer software, and the maximum position deviations of the vertical, labial (buccal) and lingual directions of the mandibular midline area and molar areas in T1 and T2 groups measured. During the clinical complete dentures try-in, we observed whether there was midline deviation in the mouth of T1 group and T2 group, and whether the occlusion of posterior teeth was stable or not. RESULTS: The mean time spent on determining the centric relation of T1 and T2 groups was (41.90±2.64) min, (57.50±2.37) min respectively. Paired t test was conducted in the two groups, P < 0.01 with significant statistical difference; The mean maximum position deviation between T1 group and T2 group of the midline mandibular region in labial lingual direction was (0.32±0.14) mm, that was (0.40±0.23) mm in vertical direction; the mean maximum position deviation of molar area in buccal lingual direction was (0.35±0.23) mm and that was (0.33±0.20) mm in vertical direction. In the vertical and horizontal directions, the maximum position deviation of mandibles between group T1 and group T2 was controlled within 0.5 mm. In the process of clinical complete dentures try-in, there was no deviation from the center line of dentures. There was not warping, swinging and other poor stability phenomena in T1 and T2 groups. CONCLUSION: The digital manufacturing of simple intraoral Gothic arch-tracing device can be used to determine the centric relation of complete dentures, which can not only save time of clinical operation, but also ensure the accuracy of the centric relation.

A Comparative Study on Efficacy and Safety of Propofol versus Dexmedetomidine in Sleep Apnea Patients undergoing Drug-Induced Sleep Endoscopy: A CONSORT-Prospective, Randomized, Controlled Clinical Trial.

The aim of this study is to compare the efficacy and safety of propofol with dexmedetomidine in patients with obstructive sleep apnea hypopnea syndrome (SAHS) undergoing drug-induced sleep endoscopy (DISE). The 88 patients diagnosed with SAHS in the Affiliated Hospital of Xuzhou Medical University were randomly allocated into 2 groups (n = 44). Patients in the group dexmedetomidine (group D) received continuous intravenous infusion of dexmedetomidine 1 µg/kg over 15 minutes before the endoscopy, and propofol 2 mg/kg was intravenously administrated in the group propofol (group P). Cardiopulmonary parameters of patients were recorded. The time to fall asleep, duration of endoscopic examination, the wakeup time of patients, the number of mask ventilations for patients, the satisfaction of patients and endoscopic performers, and false positive cases of SAHS of patients were compared between the two groups. Compared with group D, mean arterial pressure (MAP) and blood oxygen saturation (SPO2) of patients in the P group were lower at the time point of T1 (P < 0.05), the duration of endoscopic examination and wakeup time of patients were obviously prolonged, the incidence of mask ventilation for patients and false positive cases of SAHS of patients was observably higher, and the satisfaction of endoscopic performers was markedly lower, but the time to fall asleep was significantly shortened (P < 0.05). Dexmedetomidine served as a novel sleep induced drug and can provide satisfactory conditions and be safely and effectively applied for endoscopy in patients with SAHS, without adverse hemodynamic effects.

Microstructure and nanoindentation analyses of low-temperature aging on the zirconia-porcelain interface.

The aim of the present study was to investigate the effects of low-temperature aging on the micro-mechanical and micro-structural properties of zirconia-porcelain interface. In total, thirty-three Y-TZP zirconia blocks were fabricated by using CAD/CAM technology, veneered with porcelains. Specimens were submitted to low-temperature aging in an autoclave at 134°C, additional 0.2MPa pressure for 0h, 5h, or 10h. Flexural strength was obtained by using three-point bending test. Micro-mechanical properties (nano-hardness (H) and reduced modulus (Er)) were investigated by nanoindentation tests. Scanning electron microscopy and X-ray diffraction analyses were performed to identify the micro-structure and fracture behavior. The flexure strength, modulus and hardness of zirconia increased after 5h aging and decreased after 10h aging. No significant alterations of the reduced modulus or hardness of porcelain were detected in the whole aging duration. Width of the zirconia-porcelain interface was extended towards the bulk of zirconia. The detachment and cracks could be observed in zirconia, and the crystal alignment was disorganized in porcelain after 5h aging and 10h aging. Mechanical properties of the veneering porcelain are not affected by low-temperature aging. However, the expansion and the alterations of micro-mechanical and micro-structural properties of zirconia-porcelain interface were detected.

Stretchable and compressible strain sensors based on carbon nanotube meshes.

Flexible strain sensors have promising applications in healthcare and human movement detection. Herein, we report stretchable and compressible strain sensors based on carbon nanotube meshes (CNTMs) with unique structures consisting of macroscopic grids and microscopic spider-web networks. The stretchable strain sensor shows good reliability for long cyclic tests and can be used for weak stimuli and large motion detection. The compressible strain sensor also shows good reliability after long cyclic tests and can be used to detect large strains induced by walking or running motion. Both the stretchable and compressible CNTM strain sensors are reliable and stable at detecting large stretching and compressing deformation.

Angle-dependent light emission from aligned multiwalled carbon nanotubes under CO(2) laser irradiation.

This paper reports the light emission from aligned multiwalled carbon nanotubes (MWNTs) under continuous wave CO(2) laser (λ = 10.6 µm) irradiation. Results indicate that the light emission is dependent on the angle θ between the laser incident direction and the nanotube axis. The relative intensity of the light emission at certain wavelengths shows a Lorentzian feature when θ varies from 0° to 90°. The Lorentzian fitting curve displays a distinct tendency between shorter (λ<600 nm) and longer wavelength (λ>700 nm). A minimum intensity was observed at θ(m) close to 67° under shorter wavelength, whereas a maximum intensity was shown at θ(m) of about 60° at longer wavelength. These results show the anisotropic property of aligned MWNTs.

The natural history and genotype-phenotype nonconcordance of HLA identical siblings with the same mutations of the 21-hydroxylase gene.

The correlation of genotype to phenotype in congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency has been investigated thoroughly since the mapping of the CYP21 gene to the short arm of chromosome 6. In most instances, it is possible to accurately predict the phenotype based on genoytpe; however, in a small number of patients, individuals with identical mutations demonstrate variable phenotypes. We report two HLA-identical brothers who represent a striking case of genotype-phenotype nonconcordance in CAH. Molecular genetic analysis showed both patients had mutations in intron 2 and exon 10 of CYP21. Both brothers underwent salt-deprivation tests at similar ages over three separate hospital admissions. Patient 1 was diagnosed with simple virilizing CAH and was able to maintain sodium balance during salt deprivation tests. Patient 2, 3 years younger, was diagnosed with salt-wasting CAH and was unable to maintain sodium balance but progressively increased his aldosterone secretion with age.

A novel semiquantitative polymerase chain reaction/enzyme digestion-based method for detection of large scale deletions/conversions of the CYP21 gene and mutation screening in Turkish families with 21-hydroxylase deficiency.

21-Hydroxylase deficiency is a recessively inherited disorder resulting from mutations in the CYP21 gene. The CYP21 gene is located along with the CYP21P pseudogene in the human leukocyte antigen major histocompatibility complex region on chromosome 6. Molecular diagnosis is difficult due to the 98% similarity of CYP21 and CYP21P genes and the fact that almost all frequently reported mutations reside on the pseudogene. Allele-specific PCR for the 8 most frequently reported point mutations was performed in 31 Turkish families with at least a single 21-hydroxylase-deficient individual. The allele frequencies of the point mutations were as follows: P30L, 0%; IVS2 (AS,A/C-G,-13), 22.5%; G110delta8nt, 3.2%; I172N, 11.4%; exon 6 cluster (I236N, V237E, M239K), 3.2%; V281L, 0%; Q318X, 8%; and R356W, 9.6%. Large deletions and gene conversions were detected by Southern blot analysis, and the allele frequencies were 9.6% and 22.5%, respectively. Sequence analysis of the gene, performed on patients with only 1 mutated allele, revealed 2 missense mutations (R339H and P435S). A novel semiquantitative PCR/enzyme digestion-based method for the detection of large scale deletions/conversions of the gene was developed for routine diagnostic purposes, and its accuracy was shown by comparison with the results of Southern blot analysis.

Prenatal diagnosis for congenital adrenal hyperplasia in 532 pregnancies.

Congenital adrenal hyperplasia (CAH) refers to a family of monogenic inherited disorders of adrenal steroidogenesis most often caused by enzyme 21-hydroxylase deficiency (21-OHD). In the classic forms of CAH (simple virilizing and salt wasting), androgen excess causes external genital ambiguity in newborn females and progressive postnatal virilization in males and females. Prenatal treatment of CAH with dexamethasone has been successfully used for over a decade. This article serves as an update on 532 pregnancies prenatally diagnosed using amniocentesis or chorionic villus sampling between 1978 and 2001 at New York Presbyterian Hospital-Weill Medical College of Cornell University. Of the 532 pregnancies, 281 were prenatally treated for CAH due to the risk of 21-hydroxylase deficiency. Follow-up telephone interviews with mothers, genetic counselors, endocrinologists, pediatricians, and obstetricians were performed in all cases. Of the pregnancies evaluated, 116 babies were affected with classic 21-OHD. Of these, 61 were female, 49 of whom were treated prenatally with dexamethasone. Dexamethasone administered at or before 9 wk gestation (in proper doses) was effective in reducing virilization. There were no statistical differences in the symptoms during pregnancy between mothers treated with dexamethasone and those not treated with dexamethasone, except for weight gain, edema, and striae, which were greater in the treated group. No significant or enduring side-effects were noted in the fetuses, indicating that dexamethasone treatment is safe. Prenatally treated newborns did not differ in weight from untreated, unaffected newborns. Based on our experience, prenatal diagnosis and proper prenatal treatment of 21-OHD are effective in significantly reducing or eliminating virilization in the newborn female. This spares the affected female the consequences of genital ambiguity, genital surgery, and possible sex misassignment.

Congenital adrenal hyperplasia (21-hydroxylase deficiency) without demonstrable genetic mutations.

Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency (21-OHD) is the most common inherited defect of adrenal steroid biosynthesis. At least 36 mutations in the CYP21 gene, which is mapped to chromosome 6p21.3, have been described. We performed genetic analysis of the CYP21 gene in a patient with classic 21-OHD CAH and her family. The entire exonic coding regions and intronic regions, as well as the -1 kb 5' upstream promoter region, were thoroughly sequenced and analyzed. Despite extensive sequencing, no mutation was found in this 3.7 kb area. The 11beta-hydroxylase defect, closely mimicking the clinical and biochemical phenotype of classic 21-OHD, was excluded by directly sequencing 2.6 kb covering the entire coding of the CYP11B1 gene. Herein we describe a phenotypically and hormonally affected patient with classic simple virilizing 21-OHD CAH who lacks a mutation in the entire CYP21 gene and coding region of the CYP11B1 gene.

A genetic defect resulting in mild low-renin hypertension.

Severe low-renin hypertension has few known causes. Apparent mineralocorticoid excess (AME) is a genetic disorder that results in severe juvenile low-renin hypertension, hyporeninemia, hypoaldosteronemia, hypokalemic alkalosis, low birth weight, failure to thrive, poor growth, and in many cases nephrocalcinosis. In 1995, it was shown that mutations in the gene (HSD11B2) encoding the 11beta-hydroxysteroid dehydrogenase type 2 enzyme (11beta-HSD2) cause AME. Typical patients with AME have defective 11beta-HSD2 activity, as evidenced by an abnormal ratio of cortisol to cortisone metabolites and by an exceedingly diminished ability to convert [11-3H]cortisol to cortisone. Recently, we have studied an unusual patient with mild low-renin hypertension and a homozygous mutation in the HSD11B2 gene. The patient came from an inbred Mennonite family, and though the mutation identified her as a patient with AME, she did not demonstrate the typical features of AME. Biochemical analysis in this patient revealed a moderately elevated cortisol to cortisone metabolite ratio. The conversion of cortisol to cortisone was 58% compared with 0-6% in typical patients with AME whereas the normal conversion is 90-95%. Molecular analysis of the HSD11B2 gene of this patient showed a homozygous C-->T transition in the second nucleotide of codon 227, resulting in a substitution of proline with leucine (P227L). The parents and sibs were heterozygous for this mutation. In vitro expression studies showed an increase in the Km (300 nM) over normal (54 nM). Because approximately 40% of patients with essential hypertension demonstrate low renin, we suggest that such patients should undergo genetic analysis of the HSD11B2 gene.

Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess.

Apparent mineralocorticoid excess (AME) is a genetic disorder causing pre- and postnatal growth failure, juvenile hypertension, hypokalemic metabolic alkalosis, and hyporeninemic hypoaldosteronism due to a deficiency of 11 beta-hydroxysteroid dehydrogenase type 2 enzyme activity (11 beta HSD2). The 11 beta HSD2 enzyme is responsible for the conversion of cortisol to the inactive metabolite cortisone and therefore protects the mineralocorticoid receptors from cortisol intoxication. Several homozygous mutations are associated with this potentially fatal disease. We have examined the phenotype, biochemical features, and genotype of 14 patients with AME. All of the patients had characteristic signs of a severe 11 beta HSD2 defect. Birth weights were significantly lower than those of their unaffected sibs. The patients were short, underweight, and hypertensive for age. Variable damage of one or more organs (kidneys, retina, heart, and central nervous system) was found in all of the patients except one. The follow-up studies of end-organ damage after 2-13 yr of treatment in six patients demonstrated significant improvement in all patients. The urinary metabolites of cortisol demonstrated an abnormal ratio with predominance of cortisol metabolites, i.e. tetrahydrocortisol plus 5 alpha-tetrahydrocortisol/tetrahydrocortisone was 6.7-33, whereas the normal ratio is 1.0. Infusion of [11-3H]cortisol resulted in little release of tritiated water, indicating the failure of the conversion of cortisol to cortisone. Thirteen mutations in the HSD11B2 gene have been previously published, and we report three new genetic mutations in two patients, one of whom was previously unreported. All of the patients had homozygous defects except one, who was a compound heterozygote. Our first case had one of the most severe mutations, resulting in the truncation of the enzyme 11 beta HSD2, and died at the age of 16 yr while receiving treatment. Three patients with identical homozygous mutations from different families had varying degrees of severity of clinical and biochemical features. Due to the small number of patients with identical mutations, it is difficult to correlate genotype with phenotype. In some cases, early and vigilant treatment of AME patients may prevent or improve the morbidity and mortality of end-organ damage such as renal or cardiovascular damage and retinopathy. The outcome of treatment in more patients may establish the efficacy of treatment.

Several homozygous mutations in the gene for 11 beta-hydroxysteroid dehydrogenase type 2 in patients with apparent mineralocorticoid excess.

Four deleterious mutations are described in the gene for HSD11B2, which encodes the type 2 isoenzyme of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD2). In seven families with one or more members affected by apparent mineralocorticoid excess, this disorder is shown to be the result of a deficiency in 11 beta HSD2. Surprisingly, the patients are all homozygous for their mutation. This results from consanguinity in two families and possibly from endogamy or a founder effect in four of the other five families. The absence of compound heterozygotes remains to be investigated.

Prenatal treatment and diagnosis of congenital adrenal hyperplasia owing to steroid 21-hydroxylase deficiency.

Since 1986, prenatal diagnosis and treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OHD) have been carried out in 239 pregnancies. In 145, diagnoses were made by amniocentesis, whereas 77 were diagnosed using chorionic villus sampling. A newly developed, rapid allele-specific polymerase chain reaction was used for DNA analysis in some cases. Of 239 pregnancies evaluated, 37 babies were affected with classical 21-OHD. Of these, 21 were females, 13 of whom were treated prenatally with dexamethasone. Dexamethasone administered at or before 10 weeks gestation (9 affected female fetuses) was effective in reducing virilization. Seven fetuses had affected female siblings (Prader stages 1-5); 3 of these were born with entirely normal female genitalia, whereas the other 4 were significantly less virilized (Prader stages 1-2) than their siblings. The remaining 2 newborns had male siblings; 1 was born with normal genitalia, and the other was Prader stage 1. No significant or enduring side-effects were noted in either the mothers or the fetuses, indicating that dexamethasone treatment is safe. Prenatally treated newborns did not differ in weight, length, or head circumference from untreated unaffected newborns. Based on our experience, proper prenatal diagnosis and treatment of 21-OHD is effective in significantly reducing or eliminating virilization in the affected female. This spares the newborn female the consequences of genital ambiguity, i.e. genital surgery, sex misassignment, and gender confusion.

A mutation in the HSD11B2 gene in a family with apparent mineralocorticoid excess.

A mutation in the HSD11B2 gene has been discovered in a consanguineous Iranian family with three sibs suffering from Apparent Mineralocorticoid Excess (AME). Sequence data demonstrate a C to T transition resulting in an R337C mutation.

Rapid deoxyribonucleic acid analysis by allele-specific polymerase chain reaction for detection of mutations in the steroid 21-hydroxylase gene.

Rapid DNA analysis based on allele-specific polymerase chain reaction (PCR) using mutation site-specific primers was developed to detect mutations in the CYP21 gene known to cause steroid 21-hydroxylase deficiency. In contrast to the previous method, in which PCR of genomic DNA was followed by dot blot analysis with radioactive probes and multiple rounds of stripping and reprobing for each of the 8 most common mutation sites, the results using this new method were immediately visualized after the PCR run by ethidium bromide-stained agarose gel electrophoresis. Using allele-specific PCR, mutation(s) were identified on 148 affected chromosomes out of 160 tested. Although mutation(s) were identified on only one chromosome of 11 of these patients, their parents showed a consistent pattern on DNA analysis. The only exception was that in one family, in which the parents each had a detectable mutation, a mutation was detected on only one allele of the patient. Most likely there is a mutation in the patient's other allele that could have arisen de novo or was inherited from the parent and was not evident in the transmitting parent's phenotype. When compared with the dot blot procedure, allele-specific PCR is more rapid, less labor-intensive, and avoids the use of radioactivity.

Serum steroid hormonal profiles by reversed-phase liquid chromatography in patients with 17-hydroxylase deficiency and in an affected family.

We used an optimized isocratic reversed-phase high-performance liquid-chromatographic procedure to separate and measure 12 steroid hormones, and studied the steroid hormone profiles in sera from three patients with 17-hydroxylase deficiency (17-OHD). Two of the patients were sisters, one of whom (II-3), expressing normotension and primary amenorrhea, was diagnosed on the basis of chromatographic data and followed up for seven years. The untreated patients had obvious abnormalities on chromatograms of serum extracts, characterized by markedly increased corticosterone (B) and decreased or undetectable cortisol (F) and cortisone (E). The concentration of 11-deoxycorticosterone was much greater in the patient with classical symptoms than in the normotensive patient. In all three patients, concentrations of aldosterone were within the normal range, but concentrations of progesterone were much lower than in the patients with 21-hydroxylase deficiency. We evaluated the responses to corticotropin and dexamethasone. HPLC evaluation of the serum steroid profiles before and after corticotropin stimulation in the affected family showed that in the parents and one other sibling, concentrations of F before and after stimulation were within the normal ranges. The sums of the ratio of B to F before and the ratio of B to F after corticotropin stimulation (sigma B/F) in the parents and the other sibling were 0.292, 0.496, and 0.614, respectively, all much higher than the normal value (mean +/- SD: 0.164 +/- 0.038). Thus the sigma B/F value may be a hormonal marker of heterozygotes carrying this defect.

[Preventive effect of changzhankang in experimental intestinal adhesions in rats].

Intestinal adhesions were induced in rats by stabbing the terminal part of the ileum. Adhesion prevention by ibuprofen and changzhankang (CZK), which was composed by traditional Chinese medicines, was evaluated with a grading system. All of the 13 rats in the non-treated group created severe adhesions. The severity was significantly modified by orally administered CZK of 20 g/kg (in crude drugs) once or twice daily for five days (P less than 0.01 and P less than 0.05 compared with the non-treated). Intramuscular injection of ibuprofen (35 mg/kg, 3 times daily) also alleviated the severity of adhesions. There was no significant difference between the ibuprofen-treated and CZK-treated groups though some of the rats were virtually free from adhesion formation in the latter. It is plausible to expect CZK to become a promising drug used in treating intestinal adhesions, for the natural drug has greater security and less side effects than synthesized drugs.

Isocratic reversed phase high performance liquid chromatography determination of twelve natural corticosteroids in serum with on-line ultraviolet and fluorescence detection.

An isocratic reversed phase high performance liquid chromatography procedure utilizing ultraviolet and fluorescence detectors linked in series is described for the analysis of cortisone (E), cortisol (F), corticosterone (B), 11-deoxycortisol (S), 11-deoxycorticosterone (DOC), androstenedione (A), testosterone (T), 17-hydroxyprogesterone (17-OHP), progesterone (P), estriol, estradiol, estrone, prednisone acetate and dexamethasone acetate in serum. Serum specimens were extracted with ethyl ether. The optimized mobile phase was methanol + tetrahydrofuran + water (26:18:56, v/v/v). A Shim-pack ODS column was used. The recoveries were 80 to 103%. Intra- and inter-day coefficient of variance were less than 8%. The detection limit is 0.5 pmol per injection volume for estriol, estradiol, E, F and B; 1 pmol for S, A, DOC and estrone; 2 pmol for T and 17-OHP; and 4 pmol for P. Serum from normal subjects and patients with congenital adrenal hyperplasia due to 21- or 17-hydroxylase deficiency were measured, as well as samples of maternal and umbilical cord serum.

Optimization of an isocratic reversed phase liquid chromatographic system for the separation of fourteen steroids using factorial design and computer simulation.

An optimization strategy for an isocratic reversed phase high performance liquid chromatographic system (RP-HPLC) is described. Factorial design and a computer program are used to predict the retention time and resolution of fourteen steroids. An optimized rapid (less than 25 min) isocratic RP-HPLC system for the satisfactory separation of cortisone, cortisol, corticosterone, 11-deoxycortisol, 11-deoxycorticosterone, 17 alpha-hydroxyprogesterone, progesterone, androstenedione, testosterone, estrone, estradiol, estriol, prednisone acetate and dexamethasone acetate has been developed using this strategy through eight experiments.

Simultaneous measurement of eight corticosteroids by liquid chromatography, and application of the procedure to diagnosis of congenital adrenal hyperplasia.

We describe a liquid-chromatographic procedure for simultaneously determining eight steroids in serum. We used a Zorbax ODS column and a mobile phase of methanol/isopropanol/water (44/10/46, by vol), which well resolves the steroids cortisone, cortisol, corticosterone, 11-deoxycortisol, 11-deoxycorticosterone, androstenedione, 17-hydroxyprogesterone, and progesterone, but not 11-deoxycorticosterone and androstenedione. Analytical recoveries of the steroids ranged from 89.27% to 99.58%. CVs were less than 10%. Prednisone and dexamethasone do not interfere. Using this method, we studied the serum steroid profiles of six patients with congenital adrenal hyperplasia (CAH) due to deficiency of 21-hydroxylase or 17-hydroxylase. Not only could we make a clearcut diagnosis and distinguish the subtle types of CAH, but also we could investigate clinical and biochemical variants of CAH. For example, we confirmed 17-hydroxylase deficiency in a patient who was normotensive with primary amenorrhea and streak gonads.