Development of a genotyping microarray for Usher syndrome

BACKGROUND: Usher syndrome, a combination of retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction, displays a high degree of clinical and genetic heterogeneity. Three clinical subtypes can be distinguished, based on the age of onset and severity of the hearing impairment, and the presence or absence of vestibular abnormalities. Thus far, eight genes have been implicated in the syndrome, together comprising 347 protein-coding exons. METHODS: To improve DNA diagnostics for patients with Usher syndrome, we developed a genotyping microarray based on the arrayed primer extension (APEX) method. Allele-specific oligonucleotides corresponding to all 298 Usher syndrome-associated sequence variants known to date, 76 of which are novel, were arrayed. RESULTS: Approximately half of these variants were validated using original patient DNAs, which yielded an accuracy of >98%. The efficiency of the Usher genotyping microarray was tested using DNAs from 370 unrelated European and American patients with Usher syndrome. Sequence variants were identified in 64/140 (46%) patients with Usher syndrome type I, 45/189 (24%) patients with Usher syndrome type II, 6/21 (29%) patients with Usher syndrome type III and 6/20 (30%) patients with atypical Usher syndrome. The chip also identified two novel sequence variants, c.400C>T (p.R134X) in PCDH15 and c.1606T>C (p.C536S) in USH2A. CONCLUSION: The Usher genotyping microarray is a versatile and affordable screening tool for Usher syndrome. Its efficiency will improve with the addition of novel sequence variants with minimal extra costs, making it a very useful first-pass screening tool.

Short anterior correction of the thoracolumbar/lumbar curve in King 1 idiopathic scoliosis: the behaviour of the instrumented and non-instrumented curves and the trunk balance

This is a retrospective clinical, radiological and patient outcome assessment of 21 consecutive patients with King 1 idiopathic adolescent scoliosis treated by short anterior selective fusion of the major thoracolumbar/lumbar (TL/L) curve. Three-dimensional changes of both curves, changes in trunk balance and rib hump were evaluated. The minimal follow-up was 24 months (max. 83). The Cobb angle of the TL/L curve was 52 degrees (45-67 degrees) with a flexibility of 72% (40-100%). The average length of the main curve was 5 (3-8) segments. An average of 3 (2-4) segments was fused using rigid single rod implants with side-loading screws. The Cobb angle of the thoracic curve was 33 degrees (18-50 degrees) with a flexibility of 69% (29-100%). The thoracic curve in bending was less than 20 degrees in 17 patients, and 20-25 degrees in 4 patients. In the TL/L curve there was an improvement of the Cobb angle of 67%, of the apex vertebral rotation of 51% and of the apex vertebral translation of 74%. The Cobb angle of the thoracic curve improved 29% spontaneously. Shoulder balance improved significantly from an average preoperative imbalance of 14.5-3.1 mm at the last follow-up. Seventy-five percent of the patients with preoperative positive shoulder imbalance (higher on the side of the thoracic curve) had levelled shoulders at the last follow-up. C7 offset improved from a preoperative 19.8 (0-40) to 4.8 (0-18) mm at the last follow-up. There were no significant changes in rotation, translation of the thoracic curve and the clinical rib hump. There were no significant changes in thoracic kyphosis or lumbar lordosis. The average score of the SRS-24 questionnaire at the last follow-up was 91 points (max. 120). We conclude that short anterior selective fusion of the TL/L curve in King 1 scoliosis with a thoracic curve bending to 25 degrees or less (Type 5 according to Lenke classification) results in a satisfactory correction and a balanced spine. Short fusions leave enough mobile lumbar segments for the establishment of global spinal balance. A positive shoulder imbalance is not a contraindication for this procedure. Structural interbody grafts are not necessary to maintain lumbar lordosis.

Periapical surgery and the maxillary sinus: radiographic parameters for clinical outcome

OBJECTIVE: To find out whether conventional periapical radiographs can be used to determine the risk of creating an oroantral communication (OAC) while performing periapical surgery on maxillary premolars and molars. STUDY DESIGN: One hundred thirteen periapical radiographs of maxillary premolars and molars with periapical radiolucencies indicating chronic apical periodontitis were retrospectively analyzed and classified. The surgery reports were evaluated for occurrence of perforation of the maxillary sinus and postoperative complications. RESULTS: Perforation of the sinus membrane (also referred to as the Schneiderian membrane) occurred in 12 cases (9.6%). Exposure of the membrane without rupture occurred in 15 cases (12%). It was found that the distance between the apex or the periapical lesion and the sinus floor did not serve as a predictor of a possible sinus membrane rupture. On the other hand, if the radiograph showed a distinct distance between the lesion and the sinus floor, there was an 82.5% probability that OAC would not occur. Additionally, a blurred radiographic outline of the periapical lesion did not indicate an increased risk of sinus membrane rupture. CONCLUSION: Conventional periapical radiographs cannot be used as predictors for perforation of the maxillary sinus during periapical surgery. However, radiographs with a specific distance between the periapical lesion and the sinus floor point toward a very low risk of accidental sinus perforation during periapical surgery.

Significance of primary stability for osseointegration of dental implants

AIM: To investigate the significance of the initial stability of dental implants for the establishment of osseointegration in an experimental capsule model for bone augmentation. MATERIAL AND METHODS: Sixteen male rats were used in the study. In each rat, muscle-periosteal flaps were elevated on the lateral aspect of the mandibular ramus on both sides, resulting in exposure of the bone surface. Small perforations were then produced in the ramus. A rigid, hemispherical Teflon capsule with a diameter of 6 mm and a height of 4 mm and with a hole in its middle portion, prepared to fit the circumference of an ITI HC titanium implant of 2.8 mm in diameter, was fixed to the ramus using 4 mini-screws. On one side of the jaw, the implant was placed through the hole in such a way that its apex did not make contact with the mandibular ramus (test). This placement of the implant did not ensure primary stability. On the other side of the jaw, a similar implant was placed through the hole of the capsule in such a way that contact was made between the implant and the surface of the ramus (control). This provided primary stability of the implant. After placement of the implants, the soft tissues were repositioned over the capsules and sutured. After 1, 3, 6 and 9 months, four animals were sacrificed and subjected to histometric analysis. RESULTS: The mean height of direct bone-to-implant contact of implants with primary stability was 38.8%, 52.9%, 64.6% and 81.3% of the implant length at 1, 3, 6 and 9 months, respectively. Of the bone adjacent to the implant surface, 28.1%, 28.9%, 52.6% and 69.6%, respectively, consisted of mineralized bone. At the test implants, no bone-to-implant contact was observed at any observation time or in any of these non-stabilized specimens. CONCLUSION: The findings of the present study indicate that primary implant stability is a prerequisite for successful osseointegration, and that implant instability results in fibrous encapsulation, thus confirming previously made clinical observations.

Do women have impaired regional systolic function in hypertensive heart disease? A 3-dimensional echocardiography study

AIMS: In pressure overload left ventricular (LV) hypertrophy, gender-related differences in global LV systolic function have been previously reported. The goal of this study was to determine regional systolic function of the left ventricle in male and female patients with hypertensive heart disease. METHODS AND RESULTS: Regional LV function was analyzed from multiplane transesophageal echocardiography with three-dimensional (3D) reconstruction of the left ventricle. In 24 patients (13 males and 11 females), four parallel (2 basal and 2 apical) equidistant short axis cross-sections from base to apex were obtained from the reconstructed LV. In each short axis 24 wall-thickness measurements were carried out at 15 degrees intervals at end-diastole and end-systole. Thus, a total of 192 measurements were obtained in each patient. Wall thickening was calculated as difference of end-diastolic and end-systolic wall thickness, and fractional thickening as thickening divided by end-diastolic thickness. Fractional thickening and wall stress were inversely related to end-diastolic wall thickness in both, males and females. Females showed less LV systolic function when compared to males (p<0.001). However, when corrected for wall stress, which was higher in females, there was no gender difference in systolic function. CONCLUSION: There are regional differences in LV systolic function in females and males which are directly related to differences in wall stress. Thus, gender-related differences in LV regional function are load-dependent and not due to structural differences.

Emphysema and secondary pneumothorax in young adults smoking cannabis

BACKGROUND: We observed a remarkable increase in the number of young patients who presented with lung emphysema and secondary spontaneous pneumothorax (SSP) at our institution for over a period of 30 months; most of them have a common history of marijuana abuse. STUDY DESIGN: Retrospective case series. METHODS: Seventeen young patients presented with spontaneous pneumothorax with bullous lung emphysema were systematically evaluated over a period of 30 months. All were regular marijuana smokers. Clinical history, chest X-ray, CT-scan, lung function test, and laboratory and histological examinations were assessed. We compared the findings of this group (group I) with the findings of non-marijuana smoking patients (group II) in the same period. The findings of this series were also compared with the findings of 75 patients presented with pneumothorax in a previous period from January 2000 till March 2002 (group III). RESULTS: In group I, there were 17 patients: the median age of the patients was 27 years (range 19-43 years), 16 males and 1 female. All were living in Switzerland. All but one smoked marijuana daily for a mean of 8.8 years and tobacco for 11.8 years. CT-scan showed multiple bullae at the apex or significant bullous emphysema with predominance in the upper lobes only in two patients. Only two patients had reduced forced first second expiratory volume (FEV1) and one reduced vital capacity (VC) below the predicted 50%. This correlated with the subjectively asymptomatic condition of the patients. All but two patients were treated by video-assisted thoracoscopic surgery (VATS) for prevention of relapsing pneumothorax. Histology showed severe lung emphysema, inflammation, and heavily pigmented macrophages. In group II, there were 85 patients: there were 78 males, the median age was 24 years (range 17-40 years), 74 patients smoked tobacco for 13.4 years but no marijuana. CT-scan in 72 patients showed only small bullae at the apex but no significant emphysema; other clinical, laboratory, and histopathological findings showed no significant difference in group I. In group III, there were 75 patients: there were 71 males and 4 females. Mean age was 25 years (range 16-46 years). Six smoked marijuana daily for a mean of 3.2 years, and 62 smoked tobacco for 14 years. CT-scan done in 59 patients showed few small bullae at the apex but no significant lung emphysema. The presence of lung emphysema on CT-scan in group I was significantly different than in groups II and III (p=0.14). No significant difference was found among all groups in the form of clinical, laboratory, and histopathological findings. CONCLUSIONS: In case of emphysema in young individuals, marijuana abuse has to be considered in the differential diagnosis. The period of marijuana smoking seems to play an important role in the development of lung emphysema. This obviously quite frequent condition in young and so far asymptomatic patients will have medical, financial, and ethical impact, as some of these patients may be severely handicapped or even become lung transplant candidates in the future.

Pulp and periodontal healing of laterally luxated permanent teeth: results after 4 years

AIM: To evaluate the pulp and periodontal healing of laterally luxated permanent teeth. MATERIAL AND METHODS: Patients presenting with lateral luxation of permanent teeth during 2001-2002 were enrolled in this clinical study. Laterally luxated teeth were repositioned and splinted with a TTS/composite resin splint for 4 weeks. Immediate (prophylactic) root-canal treatment was performed in severely luxated teeth with radiographically closed apices. All patients received tetracycline for 10 days. Re-examinations were performed after 1, 2, 3, 6, 12 and 48 months. RESULTS: All 47 laterally luxated permanent teeth that could be followed over the entire study period survived. In 10 teeth (21.3%), a prophylactic root-canal treatment was performed within 2 weeks following injury. The remaining 37 teeth showed the following characteristics at the 4-year re-examination: 19 teeth (51.4%) had pulp survival (no clinical or radiographic signs or symptoms), nine teeth (24.3%) presented with pulp canal calcification, and pulp necrosis was seen in another nine teeth (24.3%), within the first year after trauma. None of the teeth with a radiographically open apex at the time of lateral luxation showed complications. External root resorption was only seen in one tooth. CONCLUSIONS: Laterally luxated permanent teeth with incomplete root formation have a good prognosis, with all teeth surviving in this study. The most frequent complication was pulp necrosis that was only seen in teeth with closed apices.

Impact of E22 on two-stroke and four-stroke snowmobiles

A push to reduce dependency on foreign energy and increase the use of renewable energy has many gas stations pumping ethanol blended fuels. Recreational engines typically have less complex fuel management systems than that of the automotive sector. This prevents the engine from being able to adapt to different ethanol concentrations. Using ethanol blended fuels in recreational engines raises several consumer concerns. Engine performance and emissions are both affected by ethanol blended fuels. This research focused on assessing the impact of E22 on two-stroke and four-stroke snowmobiles. Three snowmobiles were used for this study. A 2009 Arctic Cat Z1 Turbo with a closed-loop fuel injection system, a 2009 Yamaha Apex with an open-loop fuel injection system and a 2010 Polaris Rush with an open-loop fuel injection system were used to determine the impact of E22 on snowmobile engines. A five mode emissions test was conducted on each of the snowmobiles with E0 and E22 to determine the impact of the E22 fuel. All of the snowmobiles were left in stock form to assess the effect of E22 on snowmobiles currently on the trail. Brake specific emissions of the snowmobiles running on E22 were compared to that of the E0 fuel. Engine parameters such as exhaust gas temperature, fuel flow, and relative air to fuel ratio (λ) were also compared on all three snowmobiles. Combustion data using an AVL combustion analysis system was taken on the Polaris Rush. This was done to compare in-cylinder pressures, combustion duration, and location of 50% mass fraction burn. E22 decreased total hydrocarbons and carbon monoxide for all of the snowmobiles and increased carbon dioxide. Peak power increased for the closed-loop fuel injected Arctic Cat. A smaller increase of peak power was observed for the Polaris due to a partial ability of the fuel management system to adapt to ethanol. A decrease in peak power was observed for the open-loop fuel injected Yamaha.

FOSSIL PLANTS AND PALYNOMORPHS FROM THE LATE PALEOZOIC CUTLER FORMATION, EASTERN PARADOX BASIN

The late Paleozoic Cutler Formation, where exposed near the modern-day town of Gateway, Colorado, has traditionally been interpreted as the product of alluvial fan deposition within the easternmost portion of the Paradox Basin. The Paradox Basin formed between the western margin of the Uncompahgre Uplift segment of the Ancestral Rocky Mountains and the western paleoshoreline of the North American portion of Pangea. The Paradox Basin region is commonly thought to have experienced semi-arid to arid conditions and warm temperatures during the Pennsylvanian and Permian. Evidence described in this paper support prior interpretations regarding paleoclimate conditions and the inferred depositional environment for the Cutler Formation near Gateway, Colorado. Plant fossils collected from the late Paleozoic Cutler Formation in The Palisade Wilderness Study Area (managed by the U.S. Department of the Interior, Bureau of Land Management) of western Colorado include Calamites, Walchia, Pecopteris, and many calamitean fragments. The flora collected is interpreted to have lived in an arid or semi-arid environment that included wet areas of limited areal extent located near the apex of an alluvial fan system. Palynological analysis of samples collected revealed the presence of the common Pennsylvanian palynomorphs Thymospora pseudothiessenii and Lophotriletes microsaetosus. These fossils suggest that warm and at least seasonally and locally wet conditions existed in the area during the time that the plants were growing. All evidence of late Paleozoic plant life collected during this study was found along the western margin of the Uncompahgre Uplift segment of the Ancestral Rocky Mountains. During the late Paleozoic, sediment was eroded from the Uncompahgre Uplift and deposited in the adjacent Paradox Basin. The preservation of plant fossils in the most proximal parts of the Paradox Basin is remarkable due to the fact that much of the proximal Cutler Formation consists of conglomerates and sandstones deposited as debris flow and by fluvial systems. The plants must have grown in a protected setting, possibly an abandoned channel on the alluvial fan, and been rapidly buried in the subsiding Paradox Basin. It is likely that there was abundant vegetation in and adjacent to low-lying wet areas at the time the Cutler Formation was deposited.

The Amplifier - v. 8,(a-1) no. 1

In this issue...Geology camp, Mrs. Dorothy Albers, Photo Club, US Olympic Skating Team, cheerleaders, Metal's Bank, M Club, Magma, Petroleum Engineering, Glee Club

Computer technology applications in surgical implant dentistry: a systematic review

PURPOSE: To assess the literature on accuracy and clinical performance of computer technology applications in surgical implant dentistry. MATERIALS AND METHODS: Electronic and manual literature searches were conducted to collect information about (1) the accuracy and (2) clinical performance of computer-assisted implant systems. Meta-regression analysis was performed for summarizing the accuracy studies. Failure/complication rates were analyzed using random-effects Poisson regression models to obtain summary estimates of 12-month proportions. RESULTS: Twenty-nine different image guidance systems were included. From 2,827 articles, 13 clinical and 19 accuracy studies were included in this systematic review. The meta-analysis of the accuracy (19 clinical and preclinical studies) revealed a total mean error of 0.74 mm (maximum of 4.5 mm) at the entry point in the bone and 0.85 mm at the apex (maximum of 7.1 mm). For the 5 included clinical studies (total of 506 implants) using computer-assisted implant dentistry, the mean failure rate was 3.36% (0% to 8.45%) after an observation period of at least 12 months. In 4.6% of the treated cases, intraoperative complications were reported; these included limited interocclusal distances to perform guided implant placement, limited primary implant stability, or need for additional grafting procedures. CONCLUSION: Differing levels and quantity of evidence were available for computer-assisted implant placement, revealing high implant survival rates after only 12 months of observation in different indications and a reasonable level of accuracy. However, future long-term clinical data are necessary to identify clinical indications and to justify additional radiation doses, effort, and costs associated with computer-assisted implant surgery.

A systematic review on the accuracy and the clinical outcome of computer-guided template-based implant dentistry

Introduction: The aim of this systematic review was to analyze the dental literature regarding accuracy and clinical application in computer-guided template-based implant dentistry. Materials and methods: An electronic literature search complemented by manual searching was performed to gather data on accuracy and surgical, biological and prosthetic complications in connection with computer-guided implant treatment. For the assessment of accuracy meta-regression analysis was performed. Complication rates are descriptively summarized. Results: From 3120 titles after the literature search, eight articles met the inclusion criteria regarding accuracy and 10 regarding the clinical performance. Meta-regression analysis revealed a mean deviation at the entry point of 1.07 mm (95% CI: 0.76-1.22 mm) and at the apex of 1.63 mm (95% CI: 1.26-2 mm). No significant differences between the studies were found regarding method of template production or template support and stabilization. Early surgical complications occurred in 9.1%, early prosthetic complications in 18.8% and late prosthetic complications in 12% of the cases. Implant survival rates of 91-100% after an observation time of 12-60 months are reported in six clinical studies with 537 implants mainly restored immediately after flapless implantation procedures. Conclusion: Computer-guided template-based implant placement showed high implant survival rates ranging from 91% to 100%. However, a considerable number of technique-related perioperative complications were observed. Preclinical and clinical studies indicated a reasonable mean accuracy with relatively high maximum deviations. Future research should be directed to increase the number of clinical studies with longer observation periods and to improve the systems in terms of perioperative handling, accuracy and prosthetic complications.

A 5-year review of teeth filled with the noninstrumentation technology

AIM: The aim of this Case Series was to evaluate the radiographic quality of root fillings performed 5 years previously using the noninstrumentation technology (NIT)-obturation method and to assess radiographically the outcome of these root canal treatments. METHODOLOGY: Seventeen patients requiring root canal treatment participated in this study and were re-evaluated after 5 years. After instrumentation with K-Flexofiles, Calcium-Hydroxide inter-appointment dressing, re-entry and copious irrigation with NaOCl, the teeth were root filled using the NIT. RESULTS: Immediately after obturation the root fillings were (-0.78 +/- 0.11 mm) short when taking the radiographic apex as a reference point. After 60 months these values were -0.85 +/- 0.11 mm. No statistical difference was found (P > 0.05). In the periapical region, PAI rating 1 and 2 increased from 20.1% to 75.6% after 60 months. CONCLUSIONS: * This prospective Case Series demonstrated the performance of the NIT-obturation method in vivo. * Root canals filled by the reduced-pressure method using sealer combined with gutta-percha cones showed good radiographic quality. * Periapical healing after 5 years was comparable with conventional filling techniques.

[Navigation and robotics of the lateral skull base]

Computer-aided microscopic surgery of the lateral skull base is a rare intervention in daily practice. It is often a delicate and difficult minimally invasive intervention, since orientation between the petrous bone and the petrous bone apex is often challenging. In the case of aural atresia or tumors the normal anatomical landmarks are often absent, making orientation more difficult. Navigation support, together with imaging techniques such as CT, MR and angiography, enable the surgeon in such cases to perform the operation more accurately and, in some cases, also in a shorter time. However, there are no internationally standardised indications for navigated surgery on the lateral skull base. Miniaturised robotic systems are still in the initial validation phase.

Contrast-enhanced MR myelography in spontaneous intracranial hypotension: description of an artefact imitating CSF leakage

In contrast-enhanced (CE) MR myelography, hyperintense signal outside the intrathecal space in T1-weighted sequences with spectral presaturation inversion recovery (SPIR) is usually considered to be due to CSF leakage. We retrospectively investigated a hyperintense signal at the apex of the lung appearing in this sequence in patients with SIH (n = 5), CSF rhinorrhoea (n = 2), lumbar spine surgery (n = 1) and in control subjects (n = 6). Intrathecal application of contrast agent was performed in all patients before MR examination, but not in the control group. The reproducible signal increase was investigated with other fat suppression techniques and MR spectroscopy. All patients and controls showed strongly hyperintense signal at the apex of the lungs imitating CSF leakage into paraspinal tissue. This signal increase was identified as an artefact, caused by spectroscopically proven shift and broadening of water and lipid resonances (1-2 ppm) in this anatomical region. Only patients with SIH showed additional focal enhancement along the spinal nerve roots and/or in the spinal epidural space. In conclusion CE MR myelography with spectral selective fat suppression shows a reproducible cervicothoracic artefact, imitating CSF leakage. Selective water excitation technique as well as periradicular and epidural contrast collections may be helpful to discriminate between real pathological findings and artefacts.