Radiolabeling of protected tryptophan with [18F]fluoromethyl tosylate: Formation of [18F]fluoromethyl ester of tryptophan instead of 1-N-[18F]fluoromethyl tryptophan methylester.

The reaction of [18F]fluoromethyl tosylate with methyl(tert-butoxycarbonyl)-l-tryptophanate results in formation the O-alkylated ester of the tryptophan instead of alkylation of the indole nitrogen of tryptophan as initially anticipated. Treatment of protected tryptophan with NaH in dimethyl formamide (DMF) along with [18F]fluoromethyl tosylate at 130°C results in the formation of [18F]fluoromethyl(tert-butoxycarbonyl)-l-tryptophanate. Preferential formation of the O-alkylated product is postulated to be due to the hydrolysis of the ester. Confirmation of the O-alkylation was obtained by synthesizing the [19F]fluoromethyl(tert-butoxycarbonyl)-l-tryptophanate insitu and examining its NMR characteristics using multiple NMR techniques. Similar results were also obtained when reacting Boc-tryptophan-N-carboxyanhydride precursor with fluoromethyl tosylate.

Effect of 5% transdermal lidocaine patches on postoperative analgesia in dogs undergoing hemilaminectomy.

OBJECTIVES: To investigate the effect of 5% lidocaine patches on postoperative analgesia in dogs undergoing hemilaminectomy. MATERIALS AND METHODS: Client-owned dogs undergoing hemilaminectomy for a single acute intervertebral thoracolumbar disc extrusion were enrolled in this prospective, randomised, blinded clinical trial. Following methadone administration, anaesthesia was induced with propofol, and maintained with isoflurane in oxygen and fentanyl infusion, in both groups. After skin closure, two 1∙5 cm wide 5% lidocaine patch strips were attached along both sides of the wound in dogs allocated to Group L. In Group C, the two lidocaine patch strips were applied but the transparent isolating liner was not removed. Postoperatively, all dogs received a non-steroidal anti-inflammatory drug, gabapentin and diazepam. Methadone was administered according to the short form of Glasgow Composite Pain Scale with pain assessed every 2 hours for 48 hours by observers unaware of the treatment. RESULTS: Thirty-nine dogs completed the study. Demographic data, end-expiratory fraction of isoflurane, fentanyl consumption, anaesthesia and surgical times were similar between groups. The number of dogs requiring postoperative methadone and the number of doses of methadone administered were not different between groups. No macroscopic skin reaction was noticed once the patches were removed. CLINICAL SIGNIFICANCE: In this setting, 5% lidocaine patches did not provide additional postoperative analgesia in dogs undergoing hemilaminectomy.

Spatially explicit action research for coastal fisheries management.

We worked with artisanal fisherfolk along the Coromandel coast in two districts of Tamil Nadu and the Union Territory of Pondicherry in South India to map and quantify catch, gear and crew details for all fishing craft along 120 km. Spatially explicit fisheries data were collected to understand the distribution of fishing effort and to identify high pressure fishing zones. Approximately 7,945 square kilometres of fishing grounds were surveyed and 3,427 fishing trips were observed using nine GPS enabled echo-sounders operated by fishermen. Data were visualised and non parametric statistical analysis revealed distinct patterns in fishing effort, high density fishing zones and large overlaps in zones between traditional, motorised and mechanised craft. Existing marine fishing regulations for the respective regions were also evaluated and violations were mapped. Results were presented in each of the villages and then in district wide meetings with community leaders to spur discussions on resource based conflicts and fisheries management. Our findings suggest that the present trajectory of resource over-exploitation, the use of destructive fishing methods combined with the lack of compliance to current regulations will lead to a collapse of the small scale fishing industry and further intensify conflicts within the community. Recommendations made by fishing community leaders are presented and their role in local fisheries management is discussed. This study is the first of its kind for this region and can easily be replicated at regional scales to develop a better understanding of the spatial extent and nature of small scale fisheries, including conflict, for the purpose of fisheries management.

Efficacy of alternate day Directly Observed Treatment Short-course (DOTS) in skeletal tuberculosis - A retrospective study.

OBJECTIVE: To assess the efficacy of alternate day (thrice a week) Directly Observed Treatment Short-course (DOTS) regimen spanning six to nine months in providing sustained cure for skeletal tuberculosis (TB) under programmatic conditions. DESIGN: Retrospective cohort study. SETTING: An urban district tuberculosis centre in India under the Revised National Tuberculosis Programme. PARTICIPANTS: A cohort of 218 patients treated with alternate day DOTS regimen for skeletal TB between 2007 and 2012. METHODS: All patients with the diagnosis of skeletal TB registered between 2007 and 2012 who successfully completed treatment were followed up for evidence of disease recurrence or relapse using structured interviews conducted between August 2013 and October 2015 after ensuring a minimum follow up of two years. RESULTS: Of the 200 patients eligible for follow up in this study, 117 (58.5%) had a minimum follow up of two years. The remaining 83 cases could not be traced. 105 (89.7%) of these 117 patients were symptom free for two years or more after the completion of treatment. There were four cases who had a relapse of the disease within two years of completion of treatment. Eight cases were administered further ATT soon after the completion of treatment under DOTS. CONCLUSIONS: This study confirms the efficacy of the alternate day DOTS regimen in successfully treating all forms of skeletal TB, including spinal TB, with a success rate of 89.7%.

Challenges in the automated synthesis of [18F]-1-fluoroethyl tryptophan: Formation of both O- and N-alkylated products.

[18F]Fluoroethyl tosylate was synthesized using an automated "Synthra" module using ethylene di-tosylate and [18F]fluoride/K222/K2CO3 in acetonitrile. [18F]Fluoroethyl tosylate was purified by semi-preparative HPLC followed by reformulation using a C18 Sep-Pak cartridge and eluted with DMF. Using this [18F]fluoroethyl tosylate, we attempted to alkylate protected tryptophan aiming to obtain the N-[18F]fluoroethyl-t-Boc-tryptophan methyl ester. Initial attempts resulted in the formation of the O-alkylated, rather than N-alkylated product. Manual removal of the cartridge from the automated module, followed by an extended drying of the cartridge under high flow nitrogen, was required to form the desired N-alkylated product. This demonstrates that the drying process in automated modules requires modification for sensitive N-alkylation of compounds and may be essential for compounds like tryptophan methyl ester that have multiple potential sites of alkylation in their chemical structure.

Epidemiological features of skeletal tuberculosis at an urban district tuberculosis centre.

Skeletal tuberculosis is an important component of extra-pulmonary tuberculosis. It can lead to substantial morbidity and poses serious occupational and economic problem. We conducted a study in an urban District Tuberculosis Centre (DTC) to assess the burden and distribution of skeletal tuberculosis in the community. Our centre was catering to a population of 6-7 lakhs between 2007 and 2012. During this period, we treated 11,274 cases of tuberculosis. Out of these, 3086 (27.3%) were cases of extrapulmonary tuberculosis and 219 (1.94%) were cases of skeletal tuberculosis. Skeletal TB predominantly affects the young Indian population with incidence peaking in the second and third decades of life. 172 patients (78.5%) in our study were new cases. There were no drugs resistant (DRTB) skeletal TB cases till we concluded our study. Tuberculosis commonly involves joints more than long bones. The spinal column was the most commonly involved skeletal site affecting 62.6% of all cases. The rate of spinal TB in our study is much higher than that reported in literature. The high number of patients calls for close co-ordination between managing orthopaedic surgeons, treating physicians and DOT providers to ensure adequate patient care.

Management of radioactive waste gases from PET radiopharmaceutical synthesis using cost effective capture systems integrated with a cyclotron safety system.

The emphasis on the reduction of gaseous radioactive effluent associated with PET radiochemistry laboratories has increased. Various radioactive gas capture strategies have been employed historically including expensive automated compression systems. We have implemented a new cost-effective strategy employing gas capture bags with electronic feedback that are integrated with the cyclotron safety system. Our strategy is suitable for multiple automated 18F radiosynthesis modules and individual automated 11C radiosynthesis modules. We describe novel gas capture systems that minimize the risk of human error and are routinely used in our facility.

Rare giant frontal sinus osteoma mimicking fibrous dysplasia.

OBJECTIVE: To present the first report of a giant frontal sinus osteoma treated by excision and single-stage reconstruction with custom-made titanium cranioplasty and left orbital roof prostheses. CASE REPORT: A 31-year-old man with a history of chronic frontal sinusitis presented with a deforming, painless, midline forehead swelling of 11 years' duration, which had been treated unsuccessfully in Nigeria. Differential diagnosis included both benign and malignant bony tumours. Computerised tomography revealed a giant bony frontal sinus tumour extending beyond the sinus roof and breaching the left orbit, consistent with fibrous dysplasia. Given the extent of the tumour, open craniectomy was performed for surgical extirpation. Histological analysis identified multiple osteomas. This surgical approach achieved excellent cosmesis, with no evidence of recurrence at 12-month follow up. CONCLUSION: Forehead swelling may pose diagnostic and management dilemmas for the ENT surgeon; however, effective management is facilitated by a multidisciplinary approach.

Posterior Cruciate Ligament Tibial Avulsion treated with Open Reduction and Internal Fixation through the Burks and Schaffer Approach.

OBJECTIVE: To report functional outcome in Posterior Cruciate Ligament (PCL) tibial avulsion fractures treated with open reduction and internal fixation through Burks and Schaffer approach. The patient specific functional outcome measures like IKDC grading together with objective grading with stress radiographs have rarely been used -to assess PCL tibial avulsion fractures. MATERIAL AND METHODS: Twenty seven patients (21 males and 6 females) were included in the study. The mean follow up duration was 22.30±6.82 months. They were assessed using international knee documentation committee (IKDC) grades, Lysholm scoring and stress radiography. The injury severity scores (ISS) of the patients were also recorded. RESULTS: The mean Lysholm scores at the time of last follow up was 90.85±5.58. The IKDC grades achieved were normal in 20 patients, near normal in five and abnormal in two. The PCL laxity determined on active hamstring contraction stress radiography was grade I in 20 cases and grade II in seven cases. All patients had achieved bony union of tibial avulsion fractures at the time of last follow up. Statistically significant association was found between higher ISS and lower Lysholm scores. (t=3.455, p=0.0019). Good IKDC grades were associated with higher Lysholm scores (analysis of variance, F=32.51, p<.0001). There was no correlation between PCL laxity and functional outcome (t=.857, p = 0.399). CONCLUSION: PCL tibial avulsion fractures treated through Burk and Schaffer approach with open reduction and internal fixation produces good results. The early rehabilitation without cast immobilisation prevents arthrofibrosis.

Synthesis, characterization and (11) C-radiolabeling of aminophenyl benzothiazoles: structural effects on the alkylation of amino group.

Several aminophenyl benzothiazoles were prepared with a view to using them as amyloid binding agents for imaging ß-amyloid in Alzheimer's disease. These precursors were radiolabeled with (11) C-positron-emitting radioisotope using an automated synthesizer and selected radiolabeled compounds were further purified by HPLC. Our results demonstrate that changes in structure have a major influence on the radioactive yield and the ease with which the radiolabel can be introduced. Aminophenyl benzothiazoles with an attached isopropyl group resisted dialkylation perhaps due to steric hindrance caused by this group. Straight chain attachment of methyl, ethyl, butyl, and crotyl groups in the structure decreased the radiochemical yield. Notably, the o-aminophenyl benzothiazole derivatives were difficult to alkylate despite stringent experimental conditions. This reactivity difference is attributed to the hydrogen bonding characteristics of the o-amino group with the nitrogen atom of the thiazole ring.

Unusual presentation of an asymptomatic pseudomeningocele within the sphenoid sinus.

OBJECTIVE: We report the rare case of a 55-year-old woman with an asymptomatic left sphenoid sinus pseudomeningocele mimicking a mucocele. CASE REPORT: A 55-year-old woman was found to have an incidental mass in the left sphenoid sinus on computed tomography. Magnetic resonance imaging confirmed the presence of a mucocele. A left endoscopic sphenoidotomy was performed to drain the mucocele. Despite an anatomical puncture through a stenosed sphenoid ostium, alarmingly, the opening leaked cerebrospinal fluid. A dehiscent lateral wall was identified with a dural opening communicating with the sphenoid sinus. This was immediately repaired with a free nasal septal mucosal graft. Six months post-operatively, the patient remained free from cerebrospinal fluid leakage. CONCLUSION: Pseudomeningoceles are extremely rare in the absence of trauma or iatrogenic injury. Surgeons should be alert to their presence as they can mimic a unilateral mucocele or nasal polyp. Endoscopic management lends itself to a single-stage repair.

Avulsion of the puborectalis muscle is associated with asymmetry of the levator hiatus.

OBJECTIVE: To determine the degree of levator hiatal asymmetry in women with unilateral avulsion of the puborectalis muscle in order to estimate the likely effect of successful reconstruction. METHODS: We reviewed datasets of women seen between May 2005 and January 2009 in a tertiary urogynecological unit. Archived ultrasound volume datasets were analyzed for hiatal dimensions and puborectalis muscle trauma in patients with unilateral avulsion. RESULTS: From 929 eligible datasets we identified 71 patients with isolated complete unilateral tears. Unilateral avulsion was associated with a significant increase in hiatal area (P ≤ 0.002). Relative to a hypothetical normal hiatus (intact hemi-area × 2), avulsion was associated with a larger hiatus on Valsalva maneuver (+2.1 cm(2) or 7%). CONCLUSIONS: Unilateral puborectalis muscle avulsion results in an asymmetric increase in the size of the levator hiatus. This increase is relatively minor, accounting for < 10% of hiatal area. Surgical repair of an avulsion may have only limited effects on hiatal dimensions.

Predicting the site of attachment of sinonasal inverted papilloma.

STATEMENT OF PROBLEM: Sinonasal inverted papilloma is a benign, epithelial neoplasm, which has a propensity for malignant transformation and recurrence. The evolution of endoscopic trans-nasal surgery has facilitated less destructive and, more functionally and cosmetically acceptable approaches to this tumour. Recurrence rates have been shown to be more favourable than after traditional external approaches. Precise surgery is enhanced by pre-operative localisation of the site of tumour attachment. The aim of this study was to examine, in a prospective fashion, the predictive value of osteitis on the pre-operative CT scan of the paranasal sinuses at correctly identifying the site of attachment of sinonasal inverted papilloma. METHOD OF STUDY: Pre-operative CT scans of the paranasal sinuses in 24 patients with histology-proven sinonasal inverted papilloma were examined for osteitis, allowing a prediction of the site of attachment. Coronal reformats of thin-cut (1mm) axial CT scans were evaluated. Intra-operatively, the actual site of tumour attachment was established. A correlation between the predicted and actual site of tumour attachment was calculated. MAIN RESULT: The predictive value of the osteitis sign was 95%. PRINCIPAL CONCLUSION: Pre-operative identification of osteitis can be used in 95% of cases to accurately predict the intra-operative site of attachment of sinonasal inverted papilloma.

Acoustic analysis in asthmatics and the influence of inhaled corticosteroid therapy.

The impact of sustained inhaled corticosteroid (ICS) therapy on the larynx and pharynx was assessed using a prospective, cross-sectional, and investigator-blinded study conducted at the University Hospital Aintree, Liverpool, UK. Forty-six adults recruited from two local general practices and from general ENT clinics at our University hospital were investigated for the study. Patients were allocated to three groups according to ICS use. Laryngeal effects were measured by correlating the results of a vocal performance questionnaire, a respiratory symptom questionnaire, and measurements obtained by computerized speech analysis. Sustained vowels and connected speech were analyzed in normal and asthmatic subjects. Acoustic analysis was correlated with cellular markers of inflammation after biopsy. Regular ICS users had significantly more pharyngeal inflammation and throat discomfort (P<0.0001). Vocal performance was also worse in this group (P<0.0001). They were more likely to have hoarseness, weakness of voice, aphonia, sore throat, throat irritation, and cough (P<0.0001). All these variables were directly related to one another (P<0.0001). Multiple linear regression analysis showed that jitter was a good objective measure of hoarseness (P<0.05). Regular ICS users were significantly more likely to have abnormal jitter, shimmer, and closed-phase quotient scores (P<0.0001). There was no difference between the groups in the observed parameters of inflammation (P>0.01). A higher pharyngitis score did not correlate with any of the histological markers of inflammation (P>0.01). Local side effects are more common in asthmatics that use ICS regularly. Measures of laryngeal function are significantly worse in regular ICS users. However, histological markers and oropharyngeal redness are not reliable measures of inflammation.

Prospective, randomized cross-over trial to assess the ability of a dry-powder inhaler to reverse the local side effects of pressurized metered-dose inhalers.

OBJECTIVES: To determine whether a corticosteroid dry-powder inhaler could reverse the pharyngeal and laryngeal side effects produced by a corticosteroid pressurised metered-dose inhaler. DESIGN: Prospective, randomized, controlled, cross-over, evaluator-blinded study. SETTING: University Hospital Aintree, Liverpool, United Kingdom. PATIENTS: Thirty-seven adults recruited over a 12-month period from Ear, Nose and Throat clinics at our University hospital. Patients were randomized into three groups using a computer-generated random number list and sealed opaque envelopes. MAIN OUTCOME MEASURES: Scores were achieved on respiratory symptom and vocal performance questionnaires. Acoustic analysis was performed followed by a standardized biopsy of the posterior pharyngeal wall. Histological markers of inflammation were correlated with pharyngitis. The data were tested for normality using the Kalmogorov-Smirnov test. The Kruskal-Wallis analysis of variance was used to investigate differences between medians and ranges. The data were further investigated for correlations using the Spearman test. Discriminant analysis was used to examine the effect of the three groups on each variable. RESULTS: Discomfort scores (median and range) were significantly lower after dry-powder inhaler use than with either a spacer or water gargle (p < 0.01). These worsened after restoring pressurized metered-dose inhaler therapy. The reduction in pharyngitis in each of the three groups was not significant. Vocal performance scores improved with dry-powder inhaler use. Jitter, shimmer, and closed-phase quotient scores improved with dry-powder inhaler use (p < 0.01). Shimmer scores deteriorated once the pressurized metered-dose inhaler was restored (p < 0.01). There was no significant difference between the groups in most observed parameters of inflammation (p > 0.01). CONCLUSION: A dry-powder inhaler may alleviate the local side effects produced by a pressurized metered-dose inhaler. Laryngeal dysfunction appears to be particularly responsive to the absence of propellant. More observational and randomized controlled trials are necessary to examine existing inhalers and specifically, how and why they cause local side effects.

A primitive social circuit: vasotocin-substance P interactions modulate social behavior through a peripheral feedback mechanism in goldfish.

At its core, the polyvagal theory proposes that peptides affect simple social behaviors through influences on hindbrain autonomic processes. To test this mechanism, we compared the effects of fore- and hindbrain infusions of vasotocin (VT) on social approach behavior in goldfish. VT infusions into the 4th ventricle, which ink infusions verified did not move rostrally to the forebrain, inhibited social approach at a lower dose than did infusions into the 3rd ventricle, which did diffuse to the hindbrain. Thus, VT actions in the hindbrain appear to modulate this simple social behavior. We then identified a population of substance P (SP)-immunoreactive cells in the hindbrain that are encapsulated by putative VT terminals, and determined that those cells project to the periphery. Injecting SP peripherally, as with infusing VT centrally, inhibited social approach, and peripheral injections of an SP antagonist, but not central infusions, abolished the behavioral effects of central VT infusions. We therefore propose that VT inhibits social approach by activating SP cells in the hindbrain, which then induce changes in body state that feed back to the brain. Central VT infusions did not inhibit feeding, suggesting that this VT mechanism selectively affects appetitive social responses. Because VT projections to the hindbrain are highly conserved in vertebrates, influences on peripheral feedback processes like the one we have described in goldfish may reflect how VT affected simple social behaviors in ancestral vertebrates and thus preadapted members of this peptide family to play increasingly complex roles in social and emotional regulation in modern animals.

Prevalence of pharyngeal and laryngeal complications in adult asthmatics using inhaled corticosteroids.

OBJECTIVES: To investigate the prevalence in adults of pharyngeal and laryngeal symptoms associated with the use of inhaled corticosteroids. DESIGN: Prospective, observational and based on a structured, specifically designed postal questionnaire. SETTING: University Hospital Aintree, Liverpool, UK. PARTICIPANTS: The questionnaire was distributed to 190 patients on the basis of current inhaled corticosteroid use. Recruitment was from the databases of two local general practices. Individuals were classified as mild, moderate or severe asthmatics, using the guidelines of the British Thoracic Society. MAIN OUTCOME MEASURES: Demographic data, including smoking history, were recorded. The number, type, strength, dosing regime and duration of individual inhaler use were recorded. Specific pharyngeal and laryngeal side effects were enquired about. Co-morbidities and preventive measures were also recorded. Results were analysed using univariate and multivariate statistical tests. RESULTS: There was a 75.8 per cent response rate (144/190 questionnaires); 63 (43.8 per cent) of respondents were male and 81 (56.2 per cent) were female. The majority of our patients were either mild or moderate asthmatics. Longer use of an inhaled corticosteroid predisposed to weak voice (p = 0.0016), hoarseness (p = 0.0001) and throat irritation (p = 0.008). Hoarseness, throat irritation, sore throat and cough were observed much more frequently than anticipated. Severe asthmatics were more likely to use a spacer device compliantly (p = 0.0487; odds ratio 1.53). Side effects were more prevalent as asthma severity worsened (p = 0.0049; odds ratio 1.87). CONCLUSIONS: Inhaled corticosteroids cause sore throats, throat irritation, hoarseness and cough. Further research in this area is required in order to elucidate the mechanism of inflammation. Only then can effective preventive measures be introduced and implemented.

The inflammation produced by corticosteroid inhalers in the pharynx in asthmatics.

OBJECTIVES: To investigate inflammation of the pharyngeal mucosa caused by inhaled corticosteroids. DESIGN: Prospective, cross-sectional, single-blinded study. SETTING: University Hospital Aintree, Liverpool, UK. PATIENTS: Fifty adults were recruited from two local general practices and from general ENT clinics at our University hospital. Patients were allocated to one of four groups according to use of inhaled corticosteroids and the presence of adverse local side effects. MAIN OUTCOME MEASURES: Scores achieved on a respiratory symptom questionnaire. Histological markers of inflammation and their correlation with pharyngitis. Statistical modelling included univariate and multivariate analyses, which included multiple linear and logistic regression, and discriminant analysis. RESULTS: The regular use of inhaled corticosteroids predisposed subjects to hoarseness, weakness of voice, sore throat and throat irritation (P < 0.0001). Pharyngitis was significantly different between the groups (P < 0.0001). Furthermore, those not using an inhaled corticosteroid regularly had little or no clinically apparent pharyngitis, whereas those using an inhaled corticosteroid regularly had significantly higher pharyngitis scores (P = 0.0204). Similarly, weakness of voice (P = 0.0234), hoarseness (P < 0.001) and sore throat (P < 0.001) were also more common in those patients that used an inhaled corticosteroid on a regular basis. To our surprise, however, cellular markers of inflammation did not corroborate the appearances of clinical examination. We found that the five most important discriminators, between those that were using inhaled corticosteroid therapy regularly and those that were not, to be intra-epithelial inflammatory cells (scdf -1.2939); age (scdf 0.8389); use of a spacer device (scdf 0.5456); sore throat (scdf 0.4230) and throat irritation (scdf 0.4015). The groups were significantly different (P < 0.0001). The statistical model used, classified 68% of the cases correctly into their respective groups. CONCLUSIONS: Inhaled corticosteroids predispose to pharyngitis and an inflammatory infiltrate. However, the clinical diagnosis of pharyngitis does not correlate well with cellular inflammatory infiltrate and is therefore, not a reliable measure of underlying inflammation. We advocate caution in the use of pharyngeal erythema as a measure of underlying inflammation.

Acute disseminated encephalomyelitis after mastoid surgery in a child.

We present a case of acute disseminated encephalomyelitis after mastoid surgery in an 11-year-old child. The aim of this paper is to increase awareness about a previously unreported and an unusual neurological complication of cholesteatoma and mastoid surgery.