Distributable, Metabolic PET Reporting of Tuberculosis.

Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of disease activity difficult. Existing detection methods rely almost exclusively on bacterial culture from sputum which limits sampling to organisms on the pulmonary surface. Advances in monitoring tuberculous lesions have utilized the common glucoside [18F]FDG, yet lack specificity to the causative pathogen Mycobacterium tuberculosis (Mtb) and so do not directly correlate with pathogen viability. Here we show that a close mimic that is also positron-emitting of the non-mammalian Mtb disaccharide trehalose - 2-[18F]fluoro-2-deoxytrehalose ([18F]FDT) - can act as a mechanism-based enzyme reporter in vivo. Use of [18F]FDT in the imaging of Mtb in diverse models of disease, including non-human primates, successfully co-opts Mtb-specific processing of trehalose to allow the specific imaging of TB-associated lesions and to monitor the effects of treatment. A pyrogen-free, direct enzyme-catalyzed process for its radiochemical synthesis allows the ready production of [18F]FDT from the most globally-abundant organic 18F-containing molecule, [18F]FDG. The full, pre-clinical validation of both production method and [18F]FDT now creates a new, bacterium-specific, clinical diagnostic candidate. We anticipate that this distributable technology to generate clinical-grade [18F]FDT directly from the widely-available clinical reagent [18F]FDG, without need for either bespoke radioisotope generation or specialist chemical methods and/or facilities, could now usher in global, democratized access to a TB-specific PET tracer.

Chemical approaches to unraveling the biology of mycobacteria.

Mycobacterium tuberculosis (Mtb), perhaps more than any other organism, is intrinsically appealing to chemical biologists. Not only does the cell envelope feature one of the most complex heteropolymers found in nature1 but many of the interactions between Mtb and its primary host (we humans) rely on lipid and not protein mediators.2,3 Many of the complex lipids, glycolipids, and carbohydrates biosynthesized by the bacterium still have unknown functions, and the complexity of the pathological processes by which tuberculosis (TB) disease progress offers many opportunities for these molecules to influence the human response. Because of the importance of TB in global public health, chemical biologists have applied a wide-ranging array of techniques to better understand the disease and improve interventions.

Effect of mesalazine on recurrence of diverticulitis in patients with symptomatic uncomplicated diverticular disease: a meta-analysis with trial sequential analysis of randomized controlled trials.

AIM: he aim was to investigate the effect of mesalazine on the recurrence of diverticulitis in patients with symptomatic uncomplicated diverticular disease (SUDD). METHODS: We performed a systematic review and conducted a search of electronic information sources to identify all randomized controlled trials (RCTs) investigating the effect of mesalazine on the recurrence of diverticulitis in patients with SUDD. We used the Cochrane tool to assess the quality of included studies. Random effects models were applied to calculate pooled outcome data. Trial sequential analysis was performed to assess the possibility of type I or II errors and to compute the information size required for conclusive meta-analysis. RESULTS: We identified six RCTs which enrolled a total of 1918 patients. There was no difference in the recurrence of diverticulitis between the mesalazine and placebo groups (OR 1.20, 95% CI 0.96-1.50, P = 0.11). A low level of heterogeneity among the studies existed (I2  = 9%, P = 0.36). When the mesalazine dose was ≤ 2 g/day, there was no difference in recurrence rate between the two groups (OR 1.10, 95% CI 0.79-1.54, P = 0.58). When the mesalazine dose was > 2 g/day, the risk of recurrence was higher in the mesalazine group (OR 1.28, 95% CI 1.02-1.62, P = 0.04). The information size was calculated as 2461 patients. Trial sequential analysis showed that the meta-analysis was conclusive and the risk of type II error was minimal. CONCLUSIONS: Mesalazine does not prevent the recurrence of diverticulitis in patients with SUDD. Further studies are required to investigate the role of mesalazine as an adjunct to other medical agents in the prevention of diverticulitis in patients with SUDD.

Simple and rapid determination of zafirlukast in plasma by ultra-performance liquid chromatography tandem mass spectrometric method: application into pharmacokinetic study in rabbits.

Zafirlukast is a selective leukotriene receptor antagonist used for the prophylaxis and chronic treatment of asthma. The aim of the present study was to develop a simple sensitive ultra-performance liquid chromatography tandem mass spectroscopy method for rapid determination of zafirlukast in plasma. After a simple one step protein precipitation by acetonitrile, zafirlukast and montelukast (IS) were separated on Acquity UPLC BEH(TM) C18 column (50 × 2.1 mm, i.d. 1.7 µm, Waters, USA) using a mobile phase of acetonitrile:water containing 10 mM acetic acid (80:20, v/v) at a flow rate of 0.3 mL/min. Zafirlukast and IS were eluted at 0.51 and 1.1 min, respectively with a total run time of only 1.5 min. The mass spectrometric determination was carried out using an electrospray interface operated in the negative mode with multiple reactions monitoring mode. The precursor to product ion transitions of m/z 574.11>462.07 and m/z 584.2>472.1 were used to quantify zafirlukast and IS, respectively. The method was linear in the concentration range of 0.17-600 ng/mL with coefficients of determination greater than 0.996 and lower limit of quantitation of 0.17 ng/mL. Intra-day and inter-day accuracies were 88.3-113.9% and the precisions were ≤ 12.6%. Zafirlukast was found to stable under various storage and sample processing conditions as per guidelines of bio-analytical method validation. The method developed herein is simple and rapid, and was successfully applied for the pharmacokinetic study in rabbits.

Spinal anaesthesia for pelvic surgery: low concentrations of lignocaine and bupivacaine are effective with less adverse events.

BACKGROUND: The aim of this study was to compare the clinical efficacy of 5% lignocaine, 2.5% lignocaine, 0.5% bupivacaine and 0.25% bupivacaine in subarachnoid block for pelvic surgeries. METHODS: 80 adult ASA grades I and II patients of either sex between the ages of 18-60 yrs, undergoing routine pelvic surgery of short duration were included in this prospective, randomized double blind study. Patients were allotted by computer generated random number table into 4 groups of 20 patients each. Group A (n = 20): injected with 2 ml of 0.5% hyperbaric bupivacaine Group B (n = 20): injected with 2 ml of 0.25% hyperbaric bupivacaine Group C (n = 20): injected with 5% hyperbaric lignocaine Group D (n = 20): injected with 2.5% hyperbaric lignocaine The following parameters were measured every five minutes till 60 minutes and then every 15 minutes till recovery. 1. Onset of sensory block assessed by pin prick method bilaterally at middle of the shin. Maximum height of sensory block noted. 2. Onset of motor block assessed by inability to raise the leg. 3. Duration of sensory block judged as time to first postoperative analgesic requirement by the patient. 4. Duration of motor block assessed by return to Bromage scale of 1. 5. Non invasive blood pressure (NIBP) and Heart Rate- 6. Complications if any were noted -nausea, vomiting, headache, transient neurological symptoms Statistical analysis was done with Kruskal-Wallis, Mann-Whitney tests and ANOVA test. RESULTS: The groups were comparable with respect to age, weight and male to female ratio (p <0.05). Time to onset of sensory block in seconds in groups A, B, C and D was 79.5 +/- 52.26, 104.24 +/- 24.53, 33.6 +/- 14.98 and 62.50 +/- 25.05 respectively. 5% lignocaine was observed to have statistically. significant shortest onset of sensory block compared to other three groups (p <0.05). The mean onset of motor block in seconds was 137.25 +/- 60.92, 240.75 +/- 73.31, 62.30 +/- 24.56, 119.5 +/- 56.51 sec in Groups A, B, C and D respectively with 5% lignocaine observed to have statistically significant fastest onset of time compared to the other groups (p <0.05). The upper dermatomal height reached was T8 or T9 in groups A, C & D. However in group B, the upper dermatomal height reached was T 10. Duration of sensory block in minutes was 172.5 +/- 49.64, 146 p.00 +/- 35.87, 105.9 +/- 31.68 and 133.6 +/- 17.68 in groups A, B, C & D respectively. 0.5% bupivacaine was observed to have the longest duration of sensory block compared to both the groups of lignocaine (p <0.01). The duration of motor block m minutes was 159.25 +/- 53.49, 137.4 +/- 15.71, 100.5 +/- 21.81, 110.0 +/- 27.76 respectively in groups A, B, C & D. The duration of motor blockade with 0.5% bupivacaine was significantly more as compared to 5% and 2.5% lignocaine (p <0.005). Nine, one, twelve and four boluses of intravenous boluses of ephedrine were required in Groups A, B, C & D respectively. Most of the boluses were required after 30 minutes in Group A as compared to 5% lignocaine wherein the doses were required in the initial 30 minutes post spinal. Four boluses each of intravenous atropine 0.3 mg were required in 0.5% and 0.25% bupivacaine which was not statistically significant amongst the four groups. Significantly more patients in 0.5% bupivacaine required intravenous boluses of ondansetron 4 mg; five in Group A, one each in Group B and C and none in Group D (p <0.05). None of the atients showed transient neurological symptoms till 5 days postoperatively. None of the patients of this series developed post spinal headache at any time till discharge of the patient from the hospital (8-1 0 days). CONCLUSION: [corrected] For subarachnoid block for pelvic surgeries longer than two hours 0.25% bupivacaine is a better choice as compared to 0.5% bupivacaine. However for short duration surgeries lasting up to one hour, 2.5% lignocaine is a better choice as compared to 5% lignocaine as the lower concentrated solutions of bupivacaine and lignocaine are more haemodynamically stable compared to their higher concentrations and with similar duration of ensory and motor block.

Current concepts in the management of hip pain in the young adult.

Until recently, surgical management of hip disorders in adults has focused mainly on conventional total hip replacements for advanced arthritis. These have been performed mainly in the elderly, and there have been few surgical options in the younger patient. Over the past decade, the treatment of hip disorders in patients less than 55 years of age has changed rapidly; improved diagnostic techniques as well as newer diagnoses have lead to increased surgical options. This article reviews the recent literature on these advances.

Anterior cruciate ligament reconstruction in patients over 40 years using hamstring autograft.

Anterior cruciate ligament (ACL) reconstruction is becoming increasingly popular in active middle-aged patients with symptomatic instability. The purpose of this study was to retrospectively evaluate the results of ACL reconstruction in patients over the age of 40. Twenty-one patients with a median age of 44 (range 40-56) who had arthroscopically assisted reconstruction using four-stranded hamstring autograft were reviewed. RCI titanium interference screw fixation was used in the tibia, and Endobutton CL fixation in the femur. The clinical results were assessed at a mean follow-up of 2 years. The median value for the Lysholm knee score was 92 (range 74-100), and the median value for the International Knee Documentation Committee score was 83 (range 53-97). For the Tegner activity scale, the median value was 6 (range 4-8) at follow-up. The median side-to-side difference using the KT-1000 arthrometer was 2 mm (range 0-3.5 mm). Hamstring ACL reconstruction in appropriately selected middle-aged patients can yield successful and satisfactory results.

Rapid fracture healing in a patient with inherited prion disease.

There do not appear to be any reports or guidelines in the published literature regarding the outcomes of operative or conservative management of fractures in patients with known prion disease. This case report may be helpful in the clinical management of fractures in such patients.

Less tongue engorgement with lateral placement of the Esophageal Tracheal Combitube.

BACKGROUND: The conventional technique of insertion and fixation of the Esophageal Tracheal Combitube (ETC) is occasionally associated with engorgement of the tongue. This study sought to evaluate the efficacy of an alternative placement technique in reducing the incidence of this complication. METHODS: Thirty ASA I and II adult patients posted for elective surgery under general anaesthesia lasting from 30 to 120 min were randomly divided into two groups (n=15, each). In Group A, the ETC was inserted and fixed in the midline. In Group B, the ETC was inserted along the angle of the mouth and was fixed at this lateral position. Intra-operative occurrence of engorgement of the tongue, the time of such an occurrence and any complaints of post-operative discomfort were recorded. RESULTS: The overall incidence of engorgement of the tongue in Group A patients (67%) was significantly more (P<0.01) as compared with Group B (17%). The incidence significantly increased (P<0.01) with an increase in the duration of surgery in both the groups. The engorgement persisted into the post-operative period in three patients in Group A and resolved spontaneously in <15 min in each case. CONCLUSION: Lateral insertion and fixation of the ETC is an easy, safe and effective method of preventing engorgement of the tongue associated with the use of this device without compromising a leak-proof oropharyngeal cavity.

Assessment of manoeuvres required for successful blind tracheal intubation through the PAXpress.

A PAXpress (Vital Signs Inc., Barnham, UK) airway device was placed in 50 adult ASA grade I and II patients undergoing elective surgery under general anaesthesia. The alignment of the PAXpress to the larynx was scored fibreoptically. The patients were then intubated blindly through the PAXpress and the adjusting manoeuvres required for successful intubation and complications of intubation observed. Insertion of the PAXpress was successful in all patients, and intubation was successful in 42 (84%) patients. Eleven patients were intubated in the neutral position, seven with a flexion manoeuvre and 24 with an extension manoeuvre. Intubation was successful in 17/20, 18/20, 6/8 and 1/2 of patients with a fibreoptic alignment score of 1, 2, 3 and 4, respectively. When the fibreoptic alignment score was between 2 and 4 intubation was achieved predominantly with the extension manoeuvre (20/30, 66%) rather than the flexion manoeuvre (1/30, 3%) or the neutral position (5/30, 16%). Blood staining was observed in 20 patients. We conclude that blind tracheal intubation through PAXpress has a moderately good success rate and a high incidence of mucosal trauma. 'Extension' is the predominant adjusting manoeuvre required for blind tracheal intubation, especially when the alignment of the PAXpress to the larynx is poor.

Study of oral itraconazole and terbinafine pulse therapy in onychomycosis.

In this open, randomized and comparative study, the safety and efficacy of systemic intermittent itraconazole and terbinafine was examined in 30 patients with onychomycosis. The patient with positive mycological culture and also the patients with positive microscopy and negative culture were investigated. Patients were randomly assigned: 15 patients in each group received either 200mg itraconazole or 250 mg terbinafine twice daily during the first week of a 4 weeks cycle. The treatment duration was 16 weeks and was followed-up for 36 weeks. Both the treatment regimen showed significant reduction in onychomycosis affected areas after 8 weeks and maximum reduction was observed at the end of 36 weeks. At the end point of the follow-up period, the clinical cure rates (no residual deformity or with some deformity) were 86.7% in the itraconazole group and 100% in the terbinafine group. The mycological cure rates were 86.7% and 100% respectively. However, no statistically significant differences between the treatment groups were seen in clinical, mycological (P= 0.864) and severity assessment (P= 0.220). Nausea, abdominal cramp, headache, back pain and flu like syndrome are the adverse effects more frequently reported. At least one adverse effect was reported by 17 patients, of them 12 belonged to itraconazole group and 5 to terbinafine group and the difference was statistically significant (P= 0.027). The overall therapeutic effectiveness, safety and cost affectivity were in favor of Terbinafine pulse therapy.