Analgesic opioid use in a health-insured epilepsy population during 2012.

RATIONALE: Analgesic opioid use has increased dramatically in the general population. Although opioid analgesics are not indicated for the treatment of epilepsy, frequent opioid use has been reported in the epilepsy population. It is not clear whether comorbid disorders and/or epilepsy-associated injuries due to seizures foster opioid use. Our primary objective was to compare the prevalence of analgesic opioid use in an insured patient population with epilepsy to a matched control population without epilepsy. After observing increased frequency of opioid use in people with epilepsy compared with matched controls, we assessed the contribution of age, gender, pain diagnosis, and psychiatric illness as possible drivers regarding the use of opioids. METHODS: Health insurance claims and membership data from nine United States (U.S.) health plans for the year 2012 were analyzed. Individuals with epilepsy (n=10,271) were match-paired at a 1:2 ratio to individuals without epilepsy (n=20,542) within each health plan using propensity scores derived from age group, gender, and insurance type. Matched comparison groups had 53% females and 47% males with an average age of 34 years for the group with epilepsy and 33 years for controls. Each matched comparison group included 66% of individuals with commercial insurance, 30% with Medicaid insurance, and 4% with Medicare coverage. Based on prescriptions filled at least once during 2012, prevalence of analgesic opioid use was determined. The percentages of individuals with diagnosis for specific pain conditions and those with psychiatric diagnoses were also determined for the two comparison groups. RESULTS: Analgesic opioids were used by 26% of individuals in the group with epilepsy vs. 18% of matched controls (p<0.001). Compared with matched controls, the group with epilepsy had a significantly higher percentage of individuals with all 16 pain conditions examined: joint pain or stiffness (16% vs. 11%), abdominal pain (14% vs. 9%), headache (14% vs. 5%), pain in limb (12% vs. 7%), chest pain (11% vs. 6%), sprain of different parts (9% vs. 7%), sinusitis (9% vs. 7%), migraine (8% vs. 2%), lumbago (8% vs. 6%), backache (6% vs. 4%), cervicalgia (6% vs. 3%), fracture (5% vs. 3%), fibromyalgia (4% vs. 3%), chronic pain (3% vs. 1%), sciatica (1.4% vs. 1%), and jaw pain (0.4% vs. 0.1%) (all p<0.001). The prevalence of pain diagnosis was 51% in the group with epilepsy and 39% in the matched control group (p<0.0001). The prevalence of 'psychiatric diagnoses' was 27% in the group with epilepsy and 12% in the matched control group (p<0.0001). CONCLUSION: The prevalences of analgesic opioid use, psychiatric diagnoses, and 16 pain conditions were significantly higher in the patient population with epilepsy than in the control population without epilepsy. Our study also showed how opioid use rate varied by gender, age category, and depression. The reasons for the greater prevalence of opioid use in people with epilepsy are unclear. It seems that increased pain prevalence is an important driver for the higher frequency of opioid use in people with epilepsy. Psychiatric illness and other factors also appear to contribute. Further analysis including more detailed clinical information that cannot be obtained through claims data alone will be required to provide more insight into opioid use in people with epilepsy. If opioid use is higher in people with epilepsy as our results suggest, physicians managing patients with epilepsy need to pay special attention to safe opioid prescribing habits in order to prevent adverse outcomes such as abuse, addiction, diversion, misuse, and overdose.

The effects of evening bright light exposure on subsequent morning exercise performance.

We investigated the effects of evening bright light on the circadian timing of core temperature and morning exercise performance under conditions of high thermal stress. At 20:00 h, 8 males were exposed to a standardised light protocol and thereafter to either polychromatic bright light (2,500 lux at 50 cm, BL) or no light (0 lux, NL) for 30 min. The following morning, intermittent cycling exercise was undertaken followed by a 10 km time-trial in an environmental chamber set to 35°C and 60% relative humidity. Core body temperature was measured throughout. Data were analysed using a within-subjects model and presented as mean±SD. Time of the sleep-trough in core temperature occurred ~1.75 h later following BL (P=0.07). Prior to time-trial, core temperature was 0.27±0.42°C lower in BL (95%CI: -0.02 to 0.57, P=0.07). The time-trial was completed 1.43±0.63 min (0.98-1.87) faster in BL (P=0.001). Post time-trial, intestinal temperature was 38.21±0.56°C (37.84-38.57) in BL compared to 38.64±0.42°C (38.34-38.93) in NL (P=0.10). These data provide the first evidence that a 30-min exposure to bright light prior to sleep can influence exercise performance under hot conditions during the subsequent early morning.

Local anaesthetic techniques in endoscopic sinonasal surgery: a contemporaneous review.

OBJECTIVE: Endoscopic endonasal surgery is a minimally invasive technique that has revolutionised the management of complex neurosurgical, otolaryngological, skull-base and craniofacial lesions. Traditionally performed under general anaesthetic, this study explores the growing role of local anaesthetic techniques. METHOD: A contemporaneous review of modified dental techniques and intraoral anatomy provides a supportive guide for performing endoscopic sinus surgery under local anaesthetic. RESULTS: The practical procedures for four midfacial nerve blocks are described with relevance to endoscopic surgery under local anaesthetic. Anatomy, surgical technique and potential complications are discussed for the incisive foramen block, sphenopalatine ganglion block (via endonasal approach), maxillary nerve block (via the greater palatine foramen and the transoral lateral pterygoid plate approach) and transcutaneous approach to the pterygomaxillary fissure. CONCLUSION: Ultimately, such techniques may extend the safety and efficacy of endoscopic sinus surgery, limit surgical risk and increase satisfaction for patients, surgeons and healthcare managers alike.

Factors Associated with Self-Reported Dysphagia in Older Adults Receiving Meal Support.

OBJECTIVES: Dysphagia is common in older adults. However, there are no current estimates of dysphagia in community-dwelling older adults those receiving meal support. It is unknown whether dysphagia is associated with other measures of physical function (activities of daily living [ADL] ability or nutrition status). The study purposes were to determine the prevalence of self-reported dysphagia and to identify factors associated with self-reported dysphagia in community-dwelling older adults receiving meal support. DESIGN: A cross-sectional study. SETTING AND PARTICIPANTS: 476 community-dwelling older adults (78.5±0.51 years) across five Elder Nutrition Program meal services in Wisconsin participated in the study. MEASUREMENTS: Data were collected through administration of validated ADL and nutrition questionnaires (nutritional status, functional status with ADLs, chewing ability, dental conditions, and prior diagnoses of dysphagia, pneumonia, and dementia). For self-reported dysphagia, the validated 10-item eating assessment tool (EAT-10) was used. RESULTS: The prevalence of self-reported dysphagia (EAT-10 score of ≥ 3) was 20.4%. Multivariate logistic regression results indicated that poor nutritional status (OR=3.1, p=0.04), difficulty chewing (OR=2.2, p=0.03), prior dysphagia diagnosis (OR=34.8, p<0.001), prior pneumonia diagnosis (OR=2.1, p=0.04), and meal service site (OR=2.68, p=0.02) were associated with self-reported dysphagia. CONCLUSION: Approximately one in five community-dwelling older adults receiving meal support had self-reported dysphagia. Increased risk for poor nutrition, reduced chewing ability, prior dysphagia and pneumonia diagnosis, and meal service site were identified as factors associated with dysphagia on the EAT-10. Results highlight the need for further studies across more sites to identify dysphagia risk indicators in community-dwelling older adults receiving meal support state-wide.

Rheumatologists' recommended patient information when prescribing methotrexate for rheumatoid arthritis.

OBJECTIVES: Accurate communication of information concerning the risks and benefits of medications is essential for adherence and patient safety. A diverse array of information and sources makes it difficult to know exactly what to tell a patient with rheumatoid arthritis about methotrexate. OBJECTIVE: Our objective is to determine what key information patients must know about methotrexate and the key reasons they should call their doctor while they are taking methotrexate. METHODS: Three hundred and forty-four Canadian rheumatologists were sent a survey containing open-ended questions to gain uncued narrative perspectives from each individual's experience. The survey was designed to determine what must all patients taking methotrexate know and when must patients taking methotrexate call a physician? Emergent coding was used to establish a set of categories to form a checklist for coding. A second member checking survey was sent to gain confirmation and validation of themes developed from the initial survey. RESULTS: One hundred and seventy out of 344 (49.5%) surveys were completed. Regular blood testing, once weekly dosing, risk of infection, pregnancy and lactation information, alcohol limitation, potential lung toxicity, and drug interactions were thought to be important. Patients should call if they became pregnant, developed symptoms suggestive of lung toxicity, developed an infection, severe mouth sores, or were concerned about any side effects warranting the discontinuation of the medication. CONCLUSIONS: This study is the first to describe, from a rheumatologist's perspective, the key important information that all patients should know and when patients should call their doctor when taking methotrexate.

Outcomes from a Male-to-Male Promotores Intervention in an Emerging Latino Community.

Emerging Latino communities experience social isolation and lack services tailored to their culture. Few male-to-male promotores (community health workers in Spanish) interventions exist. This 6-month participatory study aimed to improve social support, healthcare access, depressive symptoms, and decrease alcohol consumption among Latino immigrant men. Promotores delivered non-directive social support to participants recruited from community venues. We analyzed baseline and 6-month questionnaires data (n = 89) using paired chi square tests. All participants were immigrants; 47% had not finished high school, 29% had depression symptoms, 35% reported past month binge drinking and 93% were uninsured. The intervention significantly improved having a usual source of care (24 to 43%), doctor's visits (41 to 62%) and dentist's visits (27 to 42%) in the past year. Other outcomes did not improve. Male promotores increased healthcare access among vulnerable Latino men. Addressing drinking behavior and depression may require longer interventions or specialized providers.

The Use of MIMS-MS-MS in field locations as an on-line quantitative environmental monitoring technique for trace contaminants in air and water.

Membrane introduction mass spectrometry (MIMS) is emerging as an important technique for on-line, real-time environmental monitoring. Because MIMS interfaces are simple and robust, they are ideally suited for operation in MS instrumentation used for in-field applications. We report the use of an on-line permeation tube to continuously infuse an isotopically labeled internal standard for continuous quantitative determinations in atmospheric and aqueous samples without the need for off-line calibration. This approach also provides important information on the operational performance of the analytical system during multi-day deployments. We report measured signal stability during on-line deployments in air and water of 7% based on variation of the internal standard response and have used this technique to quantify BTEX (benzene, toluene, ethylbenzenes, and xylenes), pinenes, naphthalene and 2-methoxyphenol (guaiacol) in urban air plumes at parts-per-billion by volume levels. Presented are several recent applications of MIMS-MS-MS for on-line environmental monitoring in atmospheric and aqueous environmental samples demonstrating laboratory, remote and mobile deployments. We also present the use of a thermally assisted MIMS interface for the direct measurement of polyaromatic hydrocarbons, alkylphenols, and other SVOCs in the low ppb range in aqueous environmental samples and discuss improvements in both the sensitivity and response times for selected SVOCs. The work presented in this paper represents significant improvements in field deployable mass spectrometric techniques, which can be applied to direct on-site analytical measurements of VOC and SVOCs in environmental samples.

Abscess of the anterior belly of the digastric muscle: a case report.

Abscess of the anterior belly of the digastric muscle has not been previously described and could pose a diagnostic and interventional dilemma. This case summarises the clinical, microbiological, radiological and surgical issues encountered and suggests learning points for clinicians posed with similar presentations. We recommend timely assessment by an appropriately trained clinician in either ear, nose and throat or oral and maxillofacial surgery, admission to a closely observable environment with airway-trained nursing staff and with potential for escalation to high dependency or intensive care in the event of airway compromise, as well as early involvement of an anaesthetist. Multimodality imaging should be performed to identify and localise an abscess collection or phlegmon, including an orthopantomogram in anticipation of odontogenic source and dental extraction as a definitive intervention. Surgical intervention for the abscess collection should be considered with consideration of the important neurovascular structures in this region.

Streptococcus gordonii's sequenced strain CH1 glucosyltransferase determines persistent but not initial colonization of teeth of rats.

OBJECTIVE: Extracellular glucan synthesis from sucrose by Streptococcus gordonii, a major dental plaque biofilm bacterium, is assumed important for colonization of teeth; but this hypothesis is un-tested in vivo. METHODS: To do so, we studied an isogenic glucosyltransferase (Gtf)-negative mutant (strain AMS12, gtfG(-)) of S. gordonii sequenced wild type (WT, strain Challis CH1, gtfG(+)), comparing their in vitro abilities to grow in the presence of glucose and sucrose and, in vivo, to colonize and persist on teeth and induce caries in rats. Weanling rats of two breeding colonies, TAN:SPFOM(OM)BR and TAN:SPFOM(OMASF)BR, eating high sucrose diet, were inoculated with either the WT (gtfG(+)), its isogenic gtfG(-) mutant, or reference strains of Streptococcus mutans. Control animals were not inoculated. RESULTS: In vitro, the gtfG(-) strain grew at least as rapidly in the presence of sucrose as its WT gtfG(+) progenitor, but formed soft colonies on sucrose agar, consistent with its lack of insoluble glucan synthesis. It also had a higher growth yield due apparently to its inability to channel carbon flow into extracellular glucan. In vivo, the gtfG(-) mutant initially colonized as did the WT but, unlike the WT, failed to persist on the teeth as shown over time. By comparison to three S. mutans strains, S. gordonii WT, despite its comparable ecological success on the teeth, was associated with only modest caries induction. Failure of the gtfG(-) mutant to persistently colonize was associated with slight diminution of caries scores by comparison with its gtfG(+) WT. CONCLUSIONS: Initial S. gordonii colonization does not depend on Gtf-G synthesis; rather, Gtf-G production determines S. gordonii's ability to persist on the teeth of sucrose-fed rats. S. gordonii appears weakly cariogenic by comparison with S. mutans reference strains.

Novel oblique radiographic projection of the temporomandibular articulation of horses.

A novel radiographic projection is described for assessing part of the temporomandibular articulation of horses. It minimises the superimposition of osseous structures of the cranium that limit the usefulness of conventional projections and permits improved imaging in cases of suspected disease.

A baseline tool for predicting response to peginterferon alfa-2a in HBeAg-positive patients with chronic hepatitis B.

BACKGROUND: Peginterferon induces off-treatment responses in approximately one-third of patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. AIM: To develop an easy-to-use baseline prediction score to identify hepatitis B virus (HBV) genotype B-/C-infected HBeAg-positive Asian patients likely to respond to peginterferon alfa-2a. METHODS: Generalised additive models, multiple logistic regression (MLR) analysis and internal validation methods were applied to data from 647 HBeAg-positive patients from China, Hong Kong and Taiwan to develop a scoring system to predict response 24 weeks after completing a 48-week course of peginterferon alfa-2a. RESULTS: Five baseline factors (age, sex, alanine aminotransferase ratio, hepatitis B surface antigen (HBsAg) level and HBV DNA level) were retained in the final MLR for HBeAg seroconversion and used to develop a scoring system from 0 to 7. Among patients with scores of 0-1, 2-3, 4 or ≥5, HBeAg seroconversion was achieved in 6.4% (6/94), 23.0% (61/265), 36.4% (67/184) and 54.8% (57/104), respectively, and a combined response (HBeAg seroconversion plus HBV DNA <2000 IU/mL) in 5.3% (5/94), 12.8% (34/265), 25.0% (46/184) and 36.5% (38/104), respectively. Among patients with scores of 0-1, 2-3, 4 or ≥5, 57.0% (53/93), 12.3% (31/253), 3.4% (6/178) and 1.0% (1/100) had HBsAg ≥20 000 IU/mL at treatment Week 12; only 3/91 (3.3%) with HBsAg ≥20 000 IU/mL experienced a combined response at 24 weeks post-treatment (negative predictive value = 97% [88/91]). CONCLUSION: A pre-treatment scoring system using readily available baseline characteristics identifies HBeAg-positive Asian patients likely to experience sustained HBeAg seroconversion after treatment with peginterferon alfa-2a.

Clinical, Immune, and Microbiome Traits of Gingivitis and Peri-implant Mucositis.

Tissues surrounding dental implants and teeth develop clinical inflammation in response to microbial stimuli. However, the literature suggests that differences exist in the microbial insult and inflammatory responses leading to gingivitis and peri-implant mucositis. In this pilot study, the authors use for the first time a systems biology approach to comprehensively evaluate clinical parameters, selected inflammatory markers, and the microbiome of subject-matched tooth and implant sites during native inflammation and in response to experimental plaque accumulation. Fifteen subjects with 2 posterior implants and corresponding contralateral teeth were examined at enrollment; at day 0, after reinstitution of gingival/mucosal health; at days 7, 14, and 21, during stent-mediated oral hygiene (OH) abstention; and at day 42, after resumption of OH. The subgingival microbiome was evaluated via 16S rRNA gene sequencing and 8 selected inflammatory markers measured in crevicular fluid. Comparison of teeth and implants via general linear models based on orthogonal polynomials showed similar responses in clinical parameters, inflammatory mediators, and proportions of individual microbial taxa during OH abstention. Implants, however, accumulated less plaque and underwent more heterogeneous shifts in microbiome structure. A multilevel, within-group, sparse partial least squares analysis of covariation of microbial, inflammatory, and clinical parameters throughout all study visits found inflammation around teeth and implants positively correlated with IL-1 alpha and IL-1 beta and with the proportions of Selenomonas, Prevotella, and 5 species-level phylotypes. Gingivitis, however, showed a stronger positive correlation with lactoferrin and IL-1ra and a stronger negative correlation with Rothia. Peri-implant mucositis, on the contrary, correlated positively with certain microbial taxa not associated with gingivitis by a previous study or the current one. In summary, differences existed between implants and tooth sites in microbiome evolution during OH abstention and in the correlation of specific inflammatory mediators and microbial taxa with clinical inflammation. Common biological features, however, were also identified for gingivitis and mucositis.

Streptococcus mutans: fructose transport, xylitol resistance, and virulence.

Streptococcus mutans, the primary etiological agent of human dental caries, possesses at least two fructose phosphotransferase systems (PTSs), encoded by fruI and fruCD. fruI is also responsible for xylitol transport. We hypothesized that fructose and xylitol transport systems do not affect virulence. Thus, colonization and cariogenicity of fruI(-) and fruCD(-) single and double mutants, their WT (UA159), and xylitol resistance (X(r)) of S. mutans were studied in rats fed a high-sucrose diet. A sucrose phosphorylase (gtfA(-)) mutant and a reference strain (NCTC-10449S) were additional controls. Recoveries of fruI mutant from the teeth were decreased, unlike those for the other strains. The fruCD mutation was associated with a slight loss of cariogenicity on enamel, whereas mutation of fruI was associated with a loss of cariogenicity in dentin. These results also suggest why xylitol inhibition of caries is paradoxically associated with spontaneous emergence of so-called X(r) S. mutans in habitual human xylitol users.

Preparation of liposomes from milk fat globule membrane phospholipids using a microfluidizer.

The isolation of milk fat globule membrane (MFGM) material from buttermilk on a commercial scale has provided a new ingredient rich in phospholipids and sphingolipids. An MFGM-derived phospholipid fraction was used to produce liposomes via a high-pressure homogenizer (Microfluidizer). This technique does not require the use of solvents or detergents, and is suitable for use in the food industry. The liposome dispersion had an average hydrodynamic diameter of 95 nm, with a broad particle-size distribution. Increasing the number of passes through the Microfluidizer, increasing the pressure, or reducing the phospholipid concentration all resulted in a smaller average liposome diameter. Changing these variables did not have a significant effect on the polydispersity of the dispersion. Electron microscopy showed that the dispersions formed had a range of structures, including unilamellar, multilamellar, and multivesicular liposomes. The composition of the MFGM phospholipid material is different from that of the phospholipids usually used for liposome production in the pharmaceutical and cosmetic industries. The MFGM-derived fraction comprises approximately 25% sphingomyelin, and the fatty acids are primarily saturated and monounsaturated. These differences are likely to affect the properties of the liposomes produced from the phospholipid material, and it may be possible to exploit the unique composition of the MFGM phospholipid fraction in the delivery of bioactive ingredients in functional foods.

Isolation and characterization of mouse nasal-associated lymphoid tissue.

A method for isolation of mouse nasal-associated lymphoid tissue (NALT), which is a principal mucosal lymphoid tissue of the respiratory tract in rodents, was developed. The paired lymphoid organs could be separated from the upper jaw by peeling away the palate where NALT was localized bilaterally on the posterior side. About 3 x 10(5) lymphocytes could be obtained from one NALT fragment. The NALT lymphocyte fraction from normal BALB/c mice contained T- and B-cells in about equal numbers, and contained about 4 times as many CD4+ T-cells as CD8+ T-cells when analyzed with a FACScan fluorescence analyzer. The composition of the NALT lymphocytes was similar to that of the lymphocytes from the portion of the nasal cavity remaining after isolation of the NALT. The NALT lymphocyte fraction from mice infected 7 days previously with influenza virus was also characterized. The numbers of NALT T- and B-cells from the infected mice were approximately 2 and 3 times higher than those of non-infected mice, respectively. In parallel with the cell increase, NALT lymphocytes produced IFN-gamma when cultured for 24 h and contained cells secreting influenza virus-specific IgA and IgG antibodies. The results suggest that this method can be successfully used for investigating cellular dynamics of mucosal immunology in the upper respiratory tract.

Factor IX Denver, ASN 346-->ASP mutation resulting in a dysfunctional protein with defective factor VIIIa interaction.

Hemophilia B is a sex-linked recessive bleeding disorder characterized by the presence of either a decreased amount of normal factor IX (FIX) or the presence of a dysfunctional FIX. We have identified a unique mutation in a family with mild hemophilia B. DNA analysis of family members revealed a single base transition in the 8th exon of the FIX gene predicting an amino acid change of Asn 346-->Asp in the catalytic domain. The FIX variant, named FIX Denver, was purified from proband plasma. Kinetic studies of factor X (FX) interactions with normal FIXa or FIXa Denver and phospholipid (PL) showed little difference in kcat but a significant difference when factor VIIIa (FVIIIa) was included in the reaction. Using kinetic assays to infer the Kd of FIXa for FVIIIa, normal FIXa had a Kd of 0.095 nM while that of FIXa Denver was 9.85 nM. The major defect caused by this point mutation is a marked decrease in the affinity of FIXa Denver for factor VIIIa.

An osteoconductive collagen/hyaluronate matrix for bone regeneration.

A new type of collagen-hyaluronate (COL/HA) matrix was synthesized by cross-linking collagen fibers with modified hyaluronate polymers bearing active formyl groups. The resulting matrix is a three-dimensional scaffold consisting of interconnected pores with an average size of 40 microm and a high pore volume/surface area ratio. The covalent nature of the bond between the collagen fibers and the modified hyaluronate was demonstrated by extended elution with phosphate buffered saline and by extraction in increasing ionic gradients. The fraction of covalently bound hyaluronate in the matrix ranged from 5 to 25 w%. The total hyaluronate content of the COL/HA matrix affected both the in vitro non-enzymatic and enzymatic degradation as well as the in vivo turnover. When implanted in cranial defects in rats, the COL/HA matrix demonstrated good biocompatibility and exhibited greater osteoconductive potential than matrices composed of either cross-linked collagen or cross-linked hyaluronate alone.

Differential expression of 11beta-hydroxysteroid dehydrogenase types 1 and 2 mRNA and glucocorticoid receptor protein during mouse embryonic development.

Accumulating evidence suggests that the actions of glucocorticoids in target tissues are critically determined by the expression of not only the glucocorticoid receptor (GR) but also the glucocorticoid-metabolizing enzymes, known as 11beta-hydroxysteroid dehydrogenase types 1 and 2 (11beta-HSD1 and 11beta-HSD2). To gain insight into the role of glucocorticoids in fetal development, the expression patterns of the two distinct 11beta-HSD isozymes and GR were studied in the mouse embryo from embryonic day 12.5 (E12.5, term = E19) to postnatal day 0.5 (P0.5) by in situ hybridization and immunohistochemistry, respectively. 11beta-HSD1 mRNA was detected in the heart as early as E12.5 and maintained thereafter. In the lung and liver, 11beta-HSD1 mRNA was first detected between E14.5 and E16.5, increased to high levels towards term and maintained after birth. Relatively low levels of 11beta-HSD1 mRNA were also detected in the kidney, adrenal glands and gastrointestinal tract at E18.5. However, the mRNA for 11beta-HSD1 was undetectable in all other embryonic tissues including the brain. In contrast, kidney was the only organ that expressed appreciable levels of 11beta-HSD2 mRNA during embryonic life. The level of 11beta-HSD2 mRNA in the kidney increased dramatically in the newborn, which coincided with expression of 11beta-HSD2 mRNA in the whisker follicle, tooth and salivary gland. Distinct from the profiles of 11beta-HSD1 and 11beta-HSD2 mRNA, GR protein was detectable in all tissues at all ages studied except for the thymus, salivary gland, and bone. Taken together, the present study demonstrates that tissue- and developmentally-stage specific expression of 11beta-HSD1 and 11beta-HSD2 as well as GR occurs in the developing mouse embryo, thus highlighting the importance of these two enzymes and GR in regulating glucocorticoid-mediated maturational events in specific tissues during murine embryonic development.

Calibration and quality assurance for rounded leaf-end MLC systems.

Multileaf collimator (MLC) systems are available on most commercial linear accelerators, and many of these MLC systems utilize a design with rounded leaf ends and linear motion of the leaves. In this kind of system, the agreement between the digital MLC position readouts and the light field or radiation field edges must be achieved with software, since the leaves do not move in a focused motion like that used for most collimator jaw systems. In this work we address a number of the calibration and quality assurance issues associated with the acceptance, commissioning, and routine clinical use of this type of MLC system. These issues are particularly important for MLCs used for various types of intensity modulated radiation therapy (IMRT) and small, conformal fields. For rounded leaf end MLCs, it is generally not possible to make both the light and radiation field edges agree with the digital readout, so differences between the two kinds of calibrations are illustrated in this work using one vendor's MLC system. It is increasingly critical that the MLC leaf calibration be very consistent with the radiation field edges, so in this work a methodology for performing accurate radiation field size calibration is discussed. A system external to the vendor's MLC control system is used to correct or handle limitations in the MLC control system. When such a system of corrections is utilized, it is found that the MLC radiation field size can be defined with an accuracy of approximately 0.3 mm, much more accurate than most vendor's specifications for MLC accuracy. Quality assurance testing for such a calibration correction system is also demonstrated.

Atlantoaxial instability in Lesch-Nyhan syndrome.

STUDY DESIGN: A clinical case report of two brothers with Lesch-Nyhan syndrome found to have atlantoaxial instability is reported. OBJECTIVES: To report the clinical and radiologic findings and the operative outcome in these patients. SUMMARY OF BACKGROUND DATA: Both patients had biochemically proven Lesch-Nyhan syndrome. No previous cases of cervical instability have been reported in this group of patients. METHODS: The first patient presented with neck pain and progressive quadriplegia. Radiology including computed tomography scanning showed fracture of the tip of the odontoid and forward subluxation of the atlas. He was treated with a C1-C2 Gallie fusion. The second patient (his brother) was found to have similar radiologic findings but had not developed quadriplegia. He has not required surgery. RESULTS: At surgery, attempted correction of the subluxation produced severe bradycardia. An in situ fusion was performed that relieved the patient's neck pain. The child's neurologic status has remained the same during a 16-month follow-up period, despite failure of the posterior wire fixation 12 months after surgery. CONCLUSIONS: Patients with Lesch-Nyhan syndrome may develop atlantoaxial instability with subsequent neck pain and quadriplegia that may be masked by their underlying disease. Posterior fusion produced symptomatic relief but no improvement in neurologic status in our patient. Posterior fusion probably should be augmented by rigid cervical immobilization until fusion is confirmed in this type of patient.