Loss-of-function mutations of Dynamin 2 promote T-ALL by enhancing IL-7 signalling.

Mutations in the DYNAMIN2 (DNM2) gene are frequently detected in human acute T-cell lymphoblastic leukemia (T-ALL), although the mechanisms linking these mutations to disease pathogenesis remain unknown. Using an ENU-based forward genetic screen for mice with erythroid phenotypes, we identified a heterozygous mouse line carrying a mutation in the GTPase domain of Dnm2 (Dnm2V265G) that induced a microcytic anemia. In vitro assays using the V265G mutant demonstrated loss of GTPase activity and impaired endocytosis that was comparable to other DNM2 mutants identified in human T-ALL. To determine the effects of DNM2 mutations in T-ALL, we bred the Dnm2V265G mice with the Lmo2 transgenic mouse model of T-ALL. Heterozygous Dnm2 mutants lacking the Lmo2 transgene displayed normal T-cell development, and did not develop T-ALL. In contrast, compound heterozygotes displayed an accelerated onset of T-ALL compared with mice carrying the Lmo2 oncogene alone. The leukemias from these mice exhibited a more immature immunophenotype and an expansion in leukemic stem cell numbers. Mechanistically, the Dnm2 mutation impaired clathrin-mediated endocytosis of the interleukin (IL)-7 receptor resulting in increased receptor density on the surface of leukemic stem cells. These findings suggest that DNM2 mutations cooperate with T-cell oncogenes by enhancing IL-7 signalling.

Small molecules demonstrate the role of dynamin as a bi-directional regulator of the exocytosis fusion pore and vesicle release.

Hormones and neurotransmitters are stored in specialised vesicles and released from excitable cells through exocytosis. During vesicle fusion with the plasma membrane, a transient fusion pore is created that enables transmitter release. The protein dynamin is known to regulate fusion pore expansion (FPE). The mechanism is unknown, but requires its oligomerisation-stimulated GTPase activity. We used a palette of small molecule dynamin modulators to reveal bi-directional regulation of FPE by dynamin and vesicle release in chromaffin cells. The dynamin inhibitors Dynole 34-2 and Dyngo 4a and the dynamin activator Ryngo 1-23 reduced or increased catecholamine released from single vesicles, respectively. Total internal reflection fluorescence (TIRF) microscopy demonstrated that dynamin stimulation with Ryngo 1-23 reduced the number of neuropeptide Y (NPY) kiss-and-run events, but not full fusion events, and slowed full fusion release kinetics. Amperometric stand-alone foot signals, representing transient kiss-and-run events, were less frequent but were of longer duration, similarly to full amperometric spikes and pre-spike foot signals. These effects are not due to alterations in vesicle size. Ryngo 1-23 action was blocked by inhibitors of actin polymerisation or myosin II. Therefore, we demonstrate using a novel pharmacological approach that dynamin not only controls FPE during exocytosis, but is a bi-directional modulator of the fusion pore that increases or decreases the amount released from a vesicle during exocytosis if it is activated or inhibited, respectively. As such, dynamin has the ability to exquisitely fine-tune transmitter release.

Minimal-trauma fracture in women with breast cancer surviving for at least 5 years from diagnosis.

SUMMARY: Minimal-trauma fracture is an important issue in breast cancer survivors, especially rib fracture. The likelihood of fracture is affected by menopausal status and a diagnosis of osteoporosis prior to breast cancer. Most women reported at least one assessment of bone mineral density. INTRODUCTION: We have investigated the self-reported frequency and pattern of minimal-trauma fracture (MTF) in breast cancer (BC) survivors at least 5 years from diagnosis, along with the use of bone mineral density (BMD) assessment. METHODS: This study was carried out within the Bupa Health Foundation Health and Wellbeing After Breast Cancer Study which is a questionnaire-based prospective cohort study of 1683 women diagnosed with their first invasive breast cancer between 2004 and 2006 and followed for at least 5 years. RESULTS: One thousand two hundred and five women, who remained free of recurrence or new breast cancer, completed the fifth annual follow-up. One hundred sixty-four (13.6%) reported at least one MTF. Rib fracture was the most common (52 fractures in 46 women). Compared with women who remained pre-/peri-menopausal, either being postmenopausal at diagnosis (OR 3.53, 95% Confidence Interval (CI) 1.09-11.44, p=0.036) or changing from pre- to postmenopausal during follow-up (OR 3.97, 95% CI 1.21-13.10, p=0.023) was associated with a higher likelihood of fracture, as was having a diagnosis of osteoporosis at the time of diagnosis (OR 1.74, 95% CI 1.00-2.99, p=0.047). Most women (64.9%) reported at least one BMD assessment. CONCLUSIONS: Overall MTF is a problem for breast cancer survivors, with rib fracture a particular issue for women in our study. Both pre-existing osteoporosis and being postmenopausal are risk factors for subsequent MTF in women treated for breast cancer. Clinicians need to be mindful of fracture prevention medication in these groups.

Metformin for overweight women at midlife: a double-blind, randomized, controlled trial.

AIM: This study was undertaken to determine whether metformin would ameliorate insulin resistance, reduce weight and waist circumference and improve lipids in obese, but not morbidly obese, euglycemic women. METHODS: Obese women (body mass index (BMI) ≥ 30 and < 40 kg/m(2) and/or waist circumference > 88 cm), aged 35-65 were randomized (1:1) to metformin 850 mg or identical placebo, twice daily for 26 weeks. The primary outcome was the change in insulin resistance determined by the homeostasis model of assessment (HOMA-IR). Secondary outcomes included fasting insulin, glucose, weight, waist circumference and BMI. RESULTS: Of the 125 women screened, 117 enrolled and 100 women, mean age 53 years, were included in the primary intention-to-treat analysis. Metformin resulted in statistically significant between-group difference in the change in HOMA-IR (change in median - 0.04 vs. placebo + 0.1, p = 0.018) and BMI (mean change - 1.00 kg/m(2); 95% confidence interval (CI) 1.37 to - 0.62 vs. placebo mean change 0.00; 95% CI - 0.29 to 0.28, p < 0.001). Statistically significant reductions in HbA1c (p = 0.008) and fasting insulin (p = 0.03) and a borderline decrease in high density lipoprotein cholesterol (p = 0.07) were also observed for metformin, compared with placebo. No effects were seen for waist circumference, fasting glucose or other lipids. CONCLUSION: Treatment of euglycemic, obese, middle-aged women with metformin 1700 mg per day reduced insulin resistance and weight compared with placebo. Further studies are needed to determine whether the use of metformin will prevent the progression of insulin resistance to type 2 diabetes mellitus in obese women.

Intended follow up of women with breast cancer at low risk of recurrence and at least 5 years from diagnosis.

BACKGROUND: Although there is evidence that minimal surveillance is compatible with an optimal outcome in women after early stage breast cancer, little is known of the surveillance that these women receive. AIMS: To describe the intended clinical follow up and patterns of use of imaging modalities in low-risk breast cancer survivors who are at least 5 years from diagnosis. METHODS: Participants in the Bupa Health Foundation Health and Wellbeing After Breast Cancer Study with stage 1 invasive breast cancer at diagnosis, who had survived free of recurrence or new primary breast cancer for at least 5 years, provided information for this analysis. RESULTS: The most common choice of physician follow up was with one doctor only (54%). Within this group, the most frequent choice was a general practitioner (GP) (63%) followed by medical oncologist (23%). Thirty-five per cent of women said that they intended to consult two doctors and within this group, the most common combination was a GP and a medical oncologist (45%). This was despite two out of three women reporting being advised that there was no need to consult a medical oncologist. Over 90% of women reported having a mammogram with, or without, breast ultrasound in the previous 12 months. There was a low rate of use of other imaging tests in the absence of clear indications. CONCLUSIONS: Minimising unnecessary medical consultations by women with breast cancer at low risk of recurrence 5 years from diagnosis will require education about the benefits of a minimal surveillance strategy.

Comparison of plain vertebral X-ray and dual-energy X-ray absorptiometry for the identification of older women for fracture prevention in primary care.

BACKGROUND: Recently, the dual-energy X-ray absorptiometry (DXA) diagnostic cut-off (T-score) for Australian Pharmaceutical Benefits Scheme (PBS) supported primary fracture prevention therapy with alendronate for older women (>70 years) has been changed from -3.0 to -2.5. AIM: To examine the impact of the expanded criteria for PBS-supported fracture prevention therapy in older women on case finding and cost. METHODS: One thousand, nine hundred and eighty-three women, median age 76 years, not previously known to have low bone mineral density by DXA or a vertebral fracture underwent DXA scanning and a thoracolumbar X-ray. A woman was considered eligible for fracture prevention therapy if she had a T-score ≤-2.5 at the femoral neck and/or the lumbar vertebrae (two to four) or at least one vertebral fracture of ≥20% deformity. RESULTS: Seven hundred and forty-six women (37.6%) met the new criteria as a case for PBS-subsidised fracture prevention therapy. Four hundred and thirty-one (21.7%) had a T-score ≤-2.5 on DXA compared with 10.6% (n = 210) with a T-score ≤-3.0. Four hundred and eighty-three (24.4%) had at least one vertebral fracture. Only 8.5% (n = 168) had both a T-score ≤-2.5 and a prevalent vertebral fracture. The cost per case found by DXA equated to $460 compared with $398 for screening by thoracolumbar X-ray. CONCLUSIONS: The use of either DXA or X-ray will identify approximately two-thirds of women aged 70 years and over who would be eligible for fracture prevention. The use of X-ray would identify a marginally larger number of women and at lower financial cost but involve substantially greater radiation exposure.

Antiplatelet drugs in elective ENT surgery.

INTRODUCTION: Oral antiplatelet drugs are increasingly being encountered in patients scheduled for elective ENT surgery. Their pre-operative cessation can have potentially serious complications in some patients, particularly those with intracoronary stents. METHODS: In order to gain an impression of current peri-operative management of patients taking antiplatelet drugs, an online survey was distributed to the Expert Panel of ENT UK, the British Association of Otolaryngologists Head and Neck Surgeons, between 13 January and 15 February 2011. RESULTS: Three hundred and three members were contacted. The response rate was 55 per cent (167 replies); 78 per cent of respondents were consultants. Results are presented in the main text. CONCLUSION AND RECOMMENDATIONS: Patients can be categorised as high or low risk, depending on their indication for taking antiplatelet drugs. Recommendations taken from the literature are given on how best to manage these two groups.

Breast reconstruction following mastectomy for invasive breast cancer is strongly influenced by demographic factors in women in Victoria, Australia.

This study explored factors associated with the likelihood of reconstruction after unilateral mastectomy and the wellbeing of women after reconstruction. Data were from a questionnaire completed on average 1.8 years after diagnosis by 1429 women in the BUPA Health and Wellbeing After Breast Cancer Study. Logistic regression was used to model factors associated with reconstruction. The Psychological General Wellbeing Questionnaire was used to assess wellbeing. A total of 25.4% of 366 women who had a unilateral mastectomy had undergone a reconstruction nearly two years after diagnosis. Being younger (p<0.001), educated beyond school (p<0.04), living in the metropolitan area (p<0.001), having private health insurance (p=0.003), not having dependent children (p=0.004) and not having radiotherapy (p<0.001) explained just over 40% of the variation in reconstruction status. There was a modest difference between women who did and did not have a reconstruction in terms of wellbeing. Demographic factors strongly influence the likelihood of reconstruction after mastectomy.

Tc99m-hepatobiliary iminodiacetic acid (HIDA) scintigraphy in clinical practice.

There have been evolutionary changes in the management of pathological conditions of the hepatobiliary system over recent years, particularly with an increasing emphasis on modern hepatobiliary surgical techniques. Concurrent advances have occurred in imaging technology and availability, leading to a greater use of ultrasound, multidetector computed tomography (CT), and magnetic resonance imaging (MRI) in the primary evaluation of hepatobiliary disease. Radionuclide imaging using technetium(99m) (Tc(99m)) hepatobiliary iminodiacetic acid (HIDA) derivatives is an established technique that complements morphological imaging, providing valuable functional information in both pre- and postoperative evaluation of patients with suspected or known hepatobiliary disease. This review discusses the current clinical indications for Tc(99m) HIDA scintigraphy using clinical cases to demonstrate how this technique continues to play a valuable diagnostic role in the assessment of the functional integrity of the hepatobiliary system.

Hilar cholangiocarcinoma: MR correlation with surgical and histological findings.

AIM: To evaluate magnetic resonance cholangiography (MRC) with high-resolution dynamic gadolinium-enhanced magnetic resonance imaging (MRI) in determining the imaging features of hilar cholangiocarcinoma that relate to tumour extent and influence resectability. MATERIALS AND METHODS: Twenty-six patients that underwent resection were reviewed. Tumour location and extent, lobar atrophy, the degree of portal vein and hepatic artery involvement were recorded. The findings were correlated with surgical and histopathological findings. RESULTS: Biliary assessment was concordant in 14 and discordant in eight of 14 stented and four of 12 non-stented patients. In 63/82 veins and 43/74 arteries results were fully concordant. The mean sensitivity, specificity, positive and negative predictive values (PPV, NPV) in predicting involvement of the main portal vein (MPV) at surgery were 83.3, 100, 100, and 92.5%; of the left main branch of the portal vein (LPV) were 100, 91.6, 93.3, and 100%; and of the right branch of the portal vein (RPV) were 87.5, 100, 100, and 87.5%. The sensitivity, specificity, PPV and NPV of MRI in determining histological involvement of the MPV was 75, 90.9, 60, and 92.5%; 100, 73.3, 73, and 100% for the LPV, and 100, 66.6, 42.8, and 100% for the RPV, respectively. CONCLUSION: MRC with high-resolution dynamic gadolinium-enhanced MRI is effective in determining tumour extent and vascular involvement, but prior stenting may lead to overestimation.

Effect of slice thickness on liver lesion detection and characterisation by multidetector CT.

The purpose of our study was to compare the effectiveness of 3.2 mm, 5 mm and 7.5 mm slice thicknesses in the detection and characterisation of liver lesions found on CT in patients with known or suspected malignant disease. 110 patients underwent portal phase imaging using four-slice MDCT. Two blinded observers independently read hard copy images at each slice thickness. The size and location of each lesion detected was recorded by each observer on a diagram of liver segmental anatomy. Each lesion was characterised as benign, malignant or indeterminate in nature. A diagnostic confidence score was allocated for each lesion on a scale of 1-4. The pathology or behaviour of lesions was assessed using surgery with intra-operative ultrasound (IOUS) and histology, or interval imaging with MRI, CT, or sonography. 294 lesions were detected, 64 (22%) of which were malignant. Both observers detected significantly more lesions on the 3.2 mm versus 7.5 mm slice thickness (p < 0.0001). Both observers detected more malignant lesions on 3.2 mm and 5 mm slice thicknesses versus 7.5 mm. As slice thickness decreased there was a significant increase in the sensitivity of malignant lesion detection for observer 1 (p < 0.001) and borderline significance for observer 2 (p = 0.07). As slice thickness decreased the proportion of lesions characterised as indeterminate by both observers fell. With thinner slices, both detection and characterisation of liver lesions were improved. A slice thickness no greater than 5 mm should be used to maximise both detection and correct characterisation of liver lesions.

Genotoxic stress-induced nuclear localization of oncoprotein YB-1 in the absence of proteolytic processing.

Y-box-binding protein 1 (YB-1) is an oncogenic transcription factor whose overexpression and nuclear localization is associated with tumor progression and drug resistance. Transcriptional activation of YB-1 in response to genotoxic stress is believed to occur in the cytoplasm through sequence-specific endoproteolytic cleavage by the 20S Proteasome, followed by nuclear translocation of cleaved YB-1. To study the proteolysis model, we developed a two-step affinity purification of endogenous YB-1 protein species and characterized the products using mass spectrometry. Whereas full-length YB-1 was readily identified, the smaller protein band thought to be activated YB-1 was identified as hnRNP A1. An antibody specific for YB-1 was generated, which revealed only one YB-1 species, even after genotoxic stress-induced nuclear YB-1 translocation. These findings warrant re-evaluation of the mechanism of YB-1 nuclear translocation and transcriptional activation. The relationship between nuclear YB-1 and tumor progression may also have to re-evaluated in some cases.

Initial outcomes from universal newborn hearing screening in Avon.

OBJECTIVE: The Avon Area Health Authority was a first-phase site for introduction of universal newborn screening in the UK. The aims of this study were: to review the programme's results to date; to assess the impact screening would have on other services (e.g. the cochlear implant programme); and to assess the longer term outcome for children identified by the screening programme. PATIENTS: All children identified by the Avon universal newborn hearing screening programme between April 2002 and July 2006. RESULTS: Fifty-four children with a bilateral hearing impairment of worse than 40 dBHL were identified from a screened population of approximately 44 000. Nine of these children were put forward for cochlear implantation, and seven had been implanted at the time of writing. Thirteen of these children were identified with possible auditory neuropathy or dys-synchrony. All the newborn hearing screening programme criteria assessed were met. CONCLUSIONS: The screening programme was effective. Some areas may need review in order to optimise patient care.

Informed consent for the study of retained tissues from postmortem examination following sudden infant death.

OBJECTIVE: To develop an approach for seeking informed consent to examine tissues retained from a previous study of sudden infant death syndrome (SIDS) as part of a study on asthma, and to document responses and participation rate. DESIGN: Pilot open-ended approach to 10 volunteer SIDS parents, followed by staged approach (newsletter, mail and telephone call) to seek consent from the target SIDS families for the asthma study. PARTICIPANTS: Parents (n = 10) of SIDS infants known to SIDS and Kids Victoria and parents of SIDS infants (n = 107) from the 1991-2 SIDS in Victoria case-control study. MAIN OUTCOMES: Qualitative responses of the piloted parents and study parents, and participation rates. RESULTS: The pilot group responses were used to refine the written material to be provided. Of the 72 families for which contact details were available, 45 gave verbal consent for contact by the Victorian Institute of Forensic Medicine regarding the asthma study, three refused and 24 did not respond to two letters. Thirty-three completed consent forms, all positive for participation in the asthma study, giving a positive response rate of 73% (33/45). CONCLUSIONS: The use of postmortem tissue for research is acceptable to the next of kin when an approach is sensitive to their concerns and needs and is made by experienced counsellors from a familiar organisation. Despite the painful memories evoked by the approach of the research group, the acceptance rate among those who could be contacted was high.

A new scoring system in Cystic Fibrosis: statistical tools for database analysis - a preliminary report.

BACKGROUND: Cystic fibrosis is the most common fatal genetic disorder in the Caucasian population. Scoring systems for assessment of Cystic fibrosis disease severity have been used for almost 50 years, without being adapted to the milder phenotype of the disease in the 21st century. The aim of this current project is to develop a new scoring system using a database and employing various statistical tools. This study protocol reports the development of the statistical tools in order to create such a scoring system. METHODS: The evaluation is based on the Cystic Fibrosis database from the cohort at the Royal Children's Hospital in Melbourne. Initially, unsupervised clustering of the all data records was performed using a range of clustering algorithms. In particular incremental clustering algorithms were used. The clusters obtained were characterised using rules from decision trees and the results examined by clinicians. In order to obtain a clearer definition of classes expert opinion of each individual's clinical severity was sought. After data preparation including expert-opinion of an individual's clinical severity on a 3 point-scale (mild, moderate and severe disease), two multivariate techniques were used throughout the analysis to establish a method that would have a better success in feature selection and model derivation: 'Canonical Analysis of Principal Coordinates' and 'Linear Discriminant Analysis'. A 3-step procedure was performed with (1) selection of features, (2) extracting 5 severity classes out of a 3 severity class as defined per expert-opinion and (3) establishment of calibration datasets. RESULTS: (1) Feature selection: CAP has a more effective "modelling" focus than DA.(2) Extraction of 5 severity classes: after variables were identified as important in discriminating contiguous CF severity groups on the 3-point scale as mild/moderate and moderate/severe, Discriminant Function (DF) was used to determine the new groups mild, intermediate moderate, moderate, intermediate severe and severe disease. (3) Generated confusion tables showed a misclassification rate of 19.1% for males and 16.5% for females, with a majority of misallocations into adjacent severity classes particularly for males. CONCLUSION: Our preliminary data show that using CAP for detection of selection features and Linear DA to derive the actual model in a CF database might be helpful in developing a scoring system. However, there are several limitations, particularly more data entry points are needed to finalize a score and the statistical tools have further to be refined and validated, with re-running the statistical methods in the larger dataset.

Improved predictive model for n-decane kinetics across species, as a component of hydrocarbon mixtures.

n-Decane is considered a major component of various fuels and industrial solvents. These hydrocarbon products are complex mixtures of hundreds of components, including straight-chain alkanes, branched chain alkanes, cycloalkanes, diaromatics, and naphthalenes. Human exposures to the jet fuel, JP-8, or to industrial solvents in vapor, aerosol, and liquid forms all have the potential to produce health effects, including immune suppression and/or neurological deficits. A physiologically based pharmacokinetic (PBPK) model has previously been developed for n-decane, in which partition coefficients (PC), fitted to 4-h exposure kinetic data, were used in preference to measured values. The greatest discrepancy between fitted and measured values was for fat, where PC values were changed from 250-328 (measured) to 25 (fitted). Such a large change in a critical parameter, without any physiological basis, greatly impedes the model's extrapolative abilities, as well as its applicability for assessing the interactions of n-decane or similar alkanes with other compounds in a mixture model. Due to these limitations, the model was revised. Our approach emphasized the use of experimentally determined PCs because many tissues had not approached steady-state concentrations by the end of the 4-h exposures. Diffusion limitation was used to describe n-decane kinetics for the brain, perirenal fat, skin, and liver. Flow limitation was used to describe the remaining rapidly and slowly perfused tissues. As expected from the high lipophilicity of this semivolatile compound (log K(ow) = 5.25), sensitivity analyses showed that parameters describing fat uptake were next to blood:air partitioning and pulmonary ventilation as critical in determining overall systemic circulation and uptake in other tissues. In our revised model, partitioning into fat took multiple days to reach steady state, which differed considerably from the previous model that assumed steady-state conditions in fat at 4 h post dosing with 1200 ppm. Due to these improvements, and particularly the reconciliation between measured and fitted partition coefficients, especially fat, we have greater confidence in using the proposed model for dose, species, and route of exposure extrapolations and as a harmonized model approach for other hydrocarbon components of mixtures.

Biopsy site selection for endobronchial ultrasound guide-sheath transbronchial biopsy of peripheral lung lesions.

BACKGROUND: Choice of biopsy method for peripheral lung lesions is usually between CT-guided fine-needle aspiration biopsy (CT FNA) and bronchoscopy. Endobronchial ultrasound guide-sheath biopsy (EBUS GS) is a new method to improve the yield of bronchoscopy. Guidance on which lesions would be appropriate for either method is needed. The aim of the study was to compare the diagnostic yields and pneumothorax rate of EBUS GS and CT FNA in terms of the location of the lesion needing biopsy, in particular, whether the lesion is touching the pleura. METHODS: Prospective series of EBUS GS were compared to retrospective review of CT FNA carried out simultaneously in a large teaching hospital. RESULTS: For EBUS GS 140 cases were carried out with mean lesion size 29 mm. Overall diagnostic sensitivity was 66%. For lesions not touching visceral pleura it was 74% compared with 35% where it was on the pleura (P < 0.01). For CT FNA 121 cases were carried out with mean lesion size 37 mm. The overall diagnostic sensitivity was 64%. Rate of pneumothorax and ICC placement in EBUS GS was 1 and 0% and in CTFNA was 28 and 6%, with P < 0.001 for both. CONCLUSION: Lesion location, in particular, connection to the visceral pleura, can improve decision-making in referral for either CT FNA or EBUS GS to maximize diagnostic yield and minimize pneumothorax rate.

Spontaneous pneumothorax in children: when is invasive treatment indicated?

A retrospective review of pneumothoraces in children presenting to a major tertiary children's hospital is described. A total of 35 cases in 31 patients of spontaneous pneumothorax were identified over a 10-year period. There was one case of bilateral pneumothorax and three cases of recurrent pneumothoraces. Twenty-four cases (69%) required intercostal tube catheter drainage for a mean of 4.9 days (range 2-10 days). Eleven cases, including two cases in CF patients, and three cases in patients with Marfan's Syndrome proceeded to a secondary surgical procedure after a continuing air leak was present for an average of 5.9 days (range 2-16 days). In follow-up studies on 11 cases, 5 (45%) were found to have apical abnormalities of the lung on CT scanning. Pneumothoraces were identified in six cases of patients with cystic fibrosis as well as four in patients with Marfan's Syndrome. This present study has suggested that unless intercostal catheter treatment resolves the air leak associated with a spontaneous pneumothorax within 5 days that surgical intervention is most likely to be required to achieve a full resolution.

Radiological anatomy of the anterior ethmoidal artery for functional endoscopic sinus surgery.

AIM: This study investigated the extent to which the anterior ethmoidal artery and anterior ethmoidal foramen could be reliably identified on routine coronal sinus computed tomography scans. Where they could be identified, the relationship of these structures with the vertical height of the skull base, and their distance from an anterior landmark, were measured. METHODS: Fifty consecutive coronal sinus computed tomography scans were viewed independently by two observers. Scans were reviewed when the observers' opinions differed. RESULTS: Inter-observer concordance was high. The anterior ethmoidal foramen was visualised in 95 per cent of cases bilaterally and in the remaining 5 per cent unilaterally. The anterior ethmoidal artery was visualised in 33 per cent of scans. The anterior ethmoidal foramen was at skull base level in 72 per cent of sides studied, and below it in the remainder. The distance from the lacrimal crest to the anterior ethmoidal foramen was 22.4 mm (mean; standard deviation 3.7). CONCLUSION: The anterior ethmoidal foramen is a reliable landmark on coronal computed tomography scans of the paranasal sinuses. From this, the position of the anterior ethmoidal artery can be inferred.

The role of (99m)technetium-labelled hepato imino diacetic acid (HIDA) scan in the management of biliary pain.

OBJECTIVE: To assess the outcome of laparoscopic cholecystectomy on the basis of an abnormal provocative (99m)technetium-labelled hepato imino diacetic acid (HIDA) scan for patients with typical biliary pain and normal trans-abdominal ultrasound (TUS) scan. PATIENTS AND METHODS: Prospective data were collected for 1201 consecutive patients with typical biliary symptoms. Patients who were found to have a normal TUS and upper GI endoscopy subsequently underwent cholescintigraphy (HIDA scan). Patients with an abnormal HIDA scan, i.e.<40% ejection fraction with Sincalide (cholecystokinin octapeptide)--were offered cholecystectomy. Symptoms and histology were reviewed postoperatively. RESULTS: In all, 48/1201 (4%) patients with typical biliary symptoms had a normal ultrasound and endoscopy; 35/48 patients had an abnormal provocative HIDA scan and all underwent laparoscopic cholecystectomy. Histology in all cases revealed chronic cholecystitis and 18 patients had sludge or microlithiasis within the gallbladder. At 6-week follow-up, 31 of the 35 patients were completely asymptomatic or improved. Furthermore, 79% of patients remained symptom-free or improved at a median follow-up of 28.5 months (range 4-70). CONCLUSIONS: HIDA scan is a useful clinical tool as an adjunct to the diagnosis and management of patients who present with typical biliary pain and a normal TUS scan.