Scintigraphic Studies Research Articles

Valor pronóstico de la gammagrafía de perfusión miocárdica en pacientes diabéticos sin lesiones coronarias

ObjectiveTo determine the prognostic value of myocardial perfusion scintigraphy-gated SPECT in patients with diabetes mellitus and without obstructive coronary artery disease. Materials and methodsThis retrospective study included consecutive patients undergoing adenosine stress-rest myocardial perfusion imaging (MPI) by 99mTc-tetrofosmin between 2009 and 2011. The patients had diabetes mellitus and coronary angiography without significant coronary lesions. In total, 37 diabetic patients (female/male: 20/17; mean age: 65.2 (range: 40-78). 29 non-diabetic patients were included wich are matched with the group of diabetic patients with positive MPI. The group of non-diabetic patients had scintigraphy with myocardial ischemia and without angiographic lesions. A 36-month clinical follow-up was performed, and major cardiac events were recorded. ResultsIn 78.3% (29/37) of diabetic patients the scintigraphic study showed myocardial ischemia, while it was negative in the 21.7%. The cardiac event rate in both groups was 6%. In diabetics with a myocardial perfusion study with myocardial ischemia, there were 3 major cardiac events. In diabetic patients with negative study had no cardiac event. In the non-diabetic control group the cardiac events rate was 3.4% (1/29). ConclusionIn diabetic patients without obstructive coronary disease, myocardial perfusion study can be predictor of cardiac events. A negative study can be an indicator of a better cardiovascular prognosis.

Synthesis of 99mTc-labeled 2-Mercaptobenzimidazole as a novel radiotracer to diagnose tumor hypoxia.

Discovery of 99mTc-labeled imidazole derivatives as a potential radiotracer for hypoxic tumor imaging is considered to be of great interest because of non-invasive detection capabilities. 2-Mercaptobenzimidazole (2-MBI) was successfully synthesized, characterized and radiolabeled with [99mTc (CO)3(H2O)3]+ intermediate to form 99mTc-2-MBI complex with radiochemical purity of ≥95% yield as observed by instant-thin layer chromatography (ITLC) and radio-high performance liquid chromatography (radio-HPLC). The 99mTc-2-MBI complex was observed to be stable in saline and serum with no noticeable decomposition at room temperature and 37 °C, respectively, over a time period of 24 h. Biodistribution results in Balb/c mice bearing S180 tumor show that 99mTc-2-MBI highly internalized in tumor tissue, also possess preferably high tumor/muscle and tumor/blood ratios 4.14 ± 0.77 and 3.91 ± 0.63, respectively at 24 h incubation. Scintigraphic imaging study shows 99mTc-2-MBI is visibly accumulated in hypoxic tumor tissue, suggesting it would be a promising radiotracer for early stage diagnosis of tumor hypoxia.

Enhancement in brain uptake of vitamin D3 nanoemulsion for treatment of cerebral ischemia: formulation, gamma scintigraphy and efficacy study in transient middle cerebral artery occlusion rat models

Aim For the treatment of cerebral ischaemia, vitamin-D3 loaded nanoemulsions were developed. Method Tween 20 and polyethylene glycol were chosen as surfactant/co-surfactant, while oleic acid as the oil phase. The formulation was characterised for various in-vitro parameters. Targeting efficiency was investigated through radiometry, gamma scintigraphy and efficacy was studied in transient middle cerebral artery occlusion (MCAo) rat model. Result Vitamin D3-nanoemulsion showed a mean size range of 49.29 ± 10.28 nm with polydispersity index 0.17 ± 0.04 and zeta potential 13.77 mV. The formulation was found stable during thermodynamic stability study and permeated within 180 min through sheep nasal mucosa (permeation coefficient 7.873 ± 0.884 cm/h). Gamma scintigraphy and radiometry assay confirmed better percentage deposition (2.53 ± 0.17%) of 99mTc-vitamin D3-nanoemulsion through nasal route compared to IV administered 99mTc-vitamin D3 solution (0.79 ± 0.03%). Magnetic Resonance Imaging (MRI) of the ischaemic model confirmed better efficacy of vitamin D3-nanoemulsion. Conclusion This work demonstrated better permeation, deposition, and efficacy of vitaminD3-nanoemulsion through the intranasal route.

Per oral pyloromyotomy utilizing a lesser curvature approach: how we do it.

The treatment of gastroparesis refractory to medical therapy has evolved to include purely endoscopic techniques. Per oral pyloromyotomy (POP) has evolved from traditional laparoscopic or open pyloroplasty to become a safe and effective minimally invasive option for patients with gastroparesis. As compared to laparoscopic pyloroplasty (LP), POP produces similar improvements in gastric emptying and symptom mitigation, while having shorter lengths of stay. There are slight variations in technique that vary by institution. Described here is a technique utilizing a lesser curve approach, with a mucosotomy closure using clips in an effort to maximize efficiency of the procedure. Preoperative workup includes a scintigraphic gastric emptying study or a wireless motility capsule study, and the Gastroparesis Cardinal Symptom Index (GCSI). After an upper endoscopy, the procedure begins with injection into the submucosal space with methylene blue in saline on the lesser curve, 3-5cm proximal to the pylorus. A 1.5cm incision is then made with the ERBE hybrid knife. A submucosal tunnel is created past the distal end of the pylorus, and the muscle is hooked, and divided with the hybrid knife. The mucosotomy is closed with clips (Boston Scientific Resolution 360, Boston, MA) after the completion of the myotomy. Post-operatively, patients are discharged home after an overnight stay with a proton pump inhibitor, sucralfate, and a full liquid diet for 2 weeks. A lesser curve approach with mucosotomy closure using clips is a safe, effective, and efficient modality for performing POP. As more centers adopt POP as a tool for gastroparesis management, the lesser curve method limits the length of the submucosal tunnel needed, and allows for wide adoption of the technique.

In vitro-in vivo correlations (IVIVCs) of deposition for drugs given by oral inhalation.

Conventional in vitro tests to assess the aerodynamic particle size distribution (APSD) from inhaler devices use simple right-angle inlets ("mouth-throats", MTs) to cascade impactors, and air is drawn through the system at a fixed flow for a fixed time. Since this arrangement differs substantially from both human oropharyngeal airway anatomy and the patterns of air flow when patients use inhalers, the ability of in vitro tests to predict in vivo deposition of pharmaceutical aerosols has been limited. MTs that mimic the human anatomy, coupled with simulated breathing patterns, have yielded estimates of lung dose from in vitro data that closely match those from in vivo gamma scintigraphic or pharmacokinetic studies. However, different models of MTs do not always yield identical data, and selection of an anatomical MT and representative inhalation profiles remains challenging. Improved in vitro - in vivo correlations (IVIVCs) for inhaled drug products could permit increased reliance on in vitro data when developing new inhaled drug products, and could ultimately result in accelerated drug product development, together with reduced research and development spending.

Submental nalbuphine exhibits improved efficacy in ameliorating acute pain in prehospital emergent conditions; a comparative study with conventional intramuscular using gamma scintigraphy

Nalbuphine (NLB) is a kappa-agonistand mu-partial antagonist, widely used for opioid withdrawal de-addiction, opioid-induced pruritis and as emergent analgesia. The present study aimed to assess the safety and efficacy of NLB in pain sensitization, through a submental route so as to provide faster management in emergent situations. In-vivo efficacy and safety studies of NLB-submental injection were assessed in Sprague-Dawley(SD) rats. For eddy's hot plate study, animals were allocated into three groups, the first group served as normal control; group II received NLB (through submental route at 1.2mg/kg); group III received NLB (through intramuscular route at 1.2mg/kg). Response latency (in terms of response latency) was measured at 10, 30 & 60min in all the experimental groups. Safety studies were carried out according to OECD 423. In-vitro release study was conducted using a cellulose dialysis membrane (12,000KDa). The biodistribution and release kinetics studies were carried out using gamma scintigraphy studies in New Zealand rabbits and humans respectively. The response latency of NLB from the submental route was found to be 7.17 (SD 1.47) seconds and in the case of the intramuscular route it was calculated as 4.00 (SD 1.26) seconds at 10min. The data depicts the better efficacy of submental injection in ameliorating pain than the intramuscular injection. Toxicity studies predict the safe profile through a submental route. The release kinetics in humans of submental NLB was 46% faster as compared to the intramuscular site of injection. The NLB injection through both routes was compared by non-invasive gamma scintigraphy technique and we found that submental injection has faster (within 10min) onset of action & distributes rapidly. The submental route of NLB is faster, more efficacious than the intramuscular route. Thus, we conclude that in the case of emergent scenarios (i.v or i.m. route is compromised), where immediate relief is necessary, the submental route is a preferred choice.

Experience with Esophagogastrointestinal Transit Scintigraphy in the Initial 229 Patients: Multiple Regions of Dysmotility Are Common

The purpose of this investigation was to review our experience with our comprehensive esophagogastrointestinal transit study in the first 229 patients. This scintigraphic study analyzes the motility of the entire gut, from the esophagus through the rectosigmoid colon. Methods: Data were reviewed for our first 2 y of experience with this examination (184 women and 45 men aged 20-79 y [mean ± SD, 44 ± 16 y]). Patients were referred with symptoms suggestive of a motility disorder. They first swallowed 111In-diethylenetriaminepentaacetic acid in water for the esophageal-swallow study and then 300 mL for a 30-min 111In water-only study, followed by 120 mL of 111In water simultaneously with the solid standardized 99mTc egg-substitute meal. Images and quantification were obtained for esophageal transit, water-only gastric emptying, water-with-solid gastric emptying, small-bowel transit, and colonic transit. Results: Of the 229 patient studies, 45 (20%) were normal. The remaining 184 (80%) had at least 1 region of dysmotility, for a total of 336 regions of abnormal motility. A single region of dysmotility was seen in 92 patients (50%), 2 regions in 50 (27%), 3 regions in 26 (14%), 4 regions in 12 (7%), and 5 regions in 4 (2%). There was a poor correlation between the results of the water-only study and water with the solid meal. Three different patterns of delayed colonic transit were seen. Patient symptoms were often not predictive of the scintigraphic findings. Conclusion: This study highlights the frequent occurrence of dysmotility in more than 1 region of the gastrointestinal tract in patients with a suspected motility disorder and the frequent concurrence of both upper- and lower-tract dysmotility in the same patients. It provides information to referring physicians regarding which motility disorders may be causing the patient symptoms, why the patient is or is not responding to the present therapy, and if and what additional workup and therapy may be needed.

Folate decorated epigallocatechin-3-gallate (EGCG) loaded PLGA nanoparticles; in-vitro and in-vivo targeting efficacy against MDA-MB-231 tumor xenograft.

Epigallocatechin-3-gallate (EGCG), a major polyphenolic constituent of green tea exhibits significant anti-cancer potential over a wide range of cancer cells. We have developed folate peptide decorated PLGA-NPs loaded with EGCG (FP-EGCG-NPs) to bind folate receptor (FR) specific breast cancer cell lines and evaluated their efficacy in pre-clinical studies. EGCG loaded PLGA nanoparticles (EGCG-NPs) were characterised for size, surface morphology, surface charge, encapsulation efficacy and in-vitro drug release kinetics. Cellular uptake and in-vitro cytotoxicities of free drug, folate peptide conjugated and unconjugated EGCG-NPs were investigated against FR positive MDA-MB-231 and MCF-7 cells. The conjugated nanoparticles exhibited promising cytotoxic potentials as well as significantly high cellular internalisation in MDA-MB-231 cells as compared to unconjugated one. It also ensured longer half life, higher plasma concentration, favourably high apoptotic potential and significantly high mitochondrial depolarization effect as compared to free EGCG. The loaded nanoparticles were radiolabeled with technetium-99m and their tumor selectivity in MDA-MB-231 tumor bearing nude mice was investigated by scintigraphic imaging study. Finally in-vivo therapeutic efficacy studies in tumor bearing nude mice were also done to evaluate the efficacy of the formulation for cancer treatment.

SUN-930 A Case of Acromegaly Secondary to Ectopic Growth Hormone-Releasing Hormone (GHRH) Secretion from a Bronchial Neuroendocrine Tumour

A Case of Acromegaly Secondary to Ectopic Growth Hormone-Releasing Hormone (GHRH) Secretion from a Bronchial Neuroendocrine TumourBackgroundAcromegaly due to ectopic GHRH secretion is a rare disorder and only accounts for less than 1% of all cases of acromegaly.CaseWe present the case of a 42-year old female with acromegaly from a bronchial neuroendocrine tumour (NET) secreting GHRH. The patient presented with gradual onset of dyspnea and wheezing. Subsequent imaging (chest X-ray, CT chest) revealed a large left-sided thoracic mass. Bronchoscopy was performed and a biopsy was taken from the mass. Initial histological examination reported small cell lung carcinoma (SCLC). Therefore, she underwent chemoradiotherapy. The patient was concurrently experiencing increased digital girth, weight gain, and enlarged tongue and was therefore referred to our endocrinology clinic for evaluation of acromegaly. Investigations revealed normal ACTH, markedly elevated IGF-1 (1031 μg/L, normal 63–215 μg/L), and non-suppressed GH levels following a 75g oral glucose tolerance test. The remainder of the pituitary panel, including TSH, prolactin, FSH, LH were all normal. An MRI sella showed a completely normal pituitary and pineal gland with no evidence of brain metastasis. She thus met clinical and biochemical criteria for acromegaly but a pituitary source could not be identified. Given her history, a paraneoplastic process or ectopic GHRH-producing tumour was suspected. Further workup showed a significantly elevated circulating GHRH levels of 73 pg/mL (normal 5 – 18 pg/mL). Subsequently, a second pathologist with expertise in NETs reviewed the same biopsy specimen. The specimen was found to be a GHRH-producing well differentiated pulmonary NET with a Ki67 index of 1.5%, and thus not a SCLC. Furthermore, a somatostatin receptor scintigraphy study was done which showed evidence of a somatostatin avid receptor rich lesion in the lung, corresponding to the known tumour. Thus, what initially appeared to be a SCLC was subsequently found to be a GHRH-secreting NET, illustrating the challenges of diagnosing these rare tumours. She was treated with intramuscular sandostatin 20mg q28days and then underwent a left pneumonectomy, resulting in biochemical resolution of her acromegaly (IGF-1 219 μg/L). Genetic testing for MEN1 was also completed as there is an association between ectopic GHRH NETs and MEN-1; however, genetic testing revealed no pathogenic variants and exon deletions or duplications suggestive of MEN-1.Learning pointsDiagnosis of acromegaly due to ectopic GHRH secretion requires high clinical suspicion by the treating clinicians (e.g., endocrinologist, oncologist) as well as review of histology by expert pathologists. Our case highlights that ectopic GHRH secretion is a rare but important cause of acromegaly, which should always be suspected when a clear pituitary cause is not identified.

Fluorescent DTPA-Silk Fibroin Nanoparticles Radiolabeled with 111In: A Dual Tool for Biodistribution and Stability Studies.

This work aims to provide an effective and novel dual tool for the biodistribution studies of biopolimeric nanoparticles by using modified silk fibroin nanoparticles as a model. This is an indispensable step in the evaluation of the applicability of biopolymeric nanoparticles as drug delivery systems. In this work, we report a new facile method for radiolabeling silk fibroin nanoparticles conjugated to the chelating agent diethylenetriamine pentaacetic acid and tagged with fluorescein isothiocyanate. Nanoparticles were characterized by means of dynamic light scattering, scanning electron microscopy, and infrared and fluorescence spectroscopy. The in vitro studies included stability in biological media and evaluation of the cytotoxicity of the nanoparticles in a cell culture. The in vivo study was focused on a scintigraphic study over 24 h conducted on New Zealand rabbits, after intra-articular injection of [111In]In-nanoparticles containing 8.03 ± 0.42 MBq. Biodistribution of the nanoparticles was also assessed ex vivo by fluorescence microscopy of post mortem biopsied organs. This radiolabeling method was reproducible and robust with high radiolabeling efficiency (∼80%) and high specific activity suitable for in vivo studies. Radiolabeled nanoparticles, having a hydrodynamic radius of 113.2 ± 2.3 nm, a polydispersity index of 0.101 ± 0.015, and a Z-potential of -30.1 ± 2.0 mV, showed an optimum retention in the articular space, without activity clearance up to 24 h post injection. Thus, an easy and robust radiolabeling method has been developed, and its applicability is demonstrated in vitro and in vivo studies, showing its value for future investigation of silk fibroin nanoparticles as versatile and stable (steady) local drug delivery systems for consideration as a therapeutic option, particularly in the treatment of joint disorders.

Spatial Standardization of Spect Brain Images With Perfusion Radiopharmaceuticals

Background. In the study of 3D images of the brain according to emission computed tomography (SPECT) there is a problem of their spatial orientation for the correct construction of sections and subsequent analysis of the symmetry of effective hemisphere perfusion. The brain on the original images can take virtually any orientation, resulting in asymmetry of distribution of radiopharmaceutical agents (RPA) on sections of parallel or perpendicular coordinate axes. In turn, this can lead to incorrect interpretation of clinical data. Objective. The purpose of the paper is development of a methodology and appropriate software module for the automated standardization of spatial orientation of the SPECT of the brain images, in particular, with 99mTc-hexamethylpropylene ( 99 mTc-HMPAO) perfusion RPA. Methods. 30 SPECT images of patients with different levels of brain perfusion were analyzed. Brain scintigraphic studies were performed with 99 mTc- HMPAO on a gamma camera E. Cam(Siemens) with LEHR collimator. SPECT was performed in 15–20 min after intravenous administration of RPA. The tomographic study included the collection of 128 projections for the 128×128 matrix, the RPA activity for intravenous administration was 740 MBq. The developed method of automated standardization of spatial orientation SPECT image of the brain was implemented in the software ScintyBrain in Matlab 2018. Results. The developed technique, based on finding the plane of symmetry of the hemispheres of the brain, allows determining the spatial orientation of the brain with an average error of 0.8–4°. The error in determining the angle of rotation of the sagittal sections increases with decreased perfusion of the frontal segments, and the frontal sections – depends on the presence of large-focal changes in the temporal and parietal divisions of the hemisphere. Conclusions. A method of automated spatial standardization of SPECT images of the brain was developed. The average error of the spatial angles of rotation of 3D images is in the range of 0.8–4°. The average computer analysis of the brain's spatial orientation takes up to 40 sec. The implementation of the presented method minimizes the subjective influence of specialists on the results of processing and analysis of scintigraphic images. In addition, the automated SPECT standardization procedure can significantly reduce the time of subsequent blending of SPECT brain images with other modalities.

The Usefulness of Scintigraphic Studies in the Assessment of Asymptomatic Bowel Disease in Patients with Primary Antibody Diseases.

Enteropathy may be the first presentation of immunodeficiency or it may occur during the course of the disease and in association with malabsorption in patients affected by primary antibody diseases. For these patients, immunoglobulin G (IgG) replacement therapy prevents infectious and non-infectious complications. Nonetheless some patients cannot achieve optimal IgG trough levels, even when treated with high Ig doses in absence of protein-losing syndromes. We investigated seven patients affected by common variable immunodeficiencies (CVIDs) and treated with high Ig doses (600–800 mg/kg/month) showing low IgG trough level. Patients underwent abdominal scintigraphy with human polyclonal immunoglobulin G labeled with 99mTc and with white blood cells labeled by 111 Indium-oxinate to investigate asymptomatic bowel inflammation. A concentration of labeled leukocytes in abdominal segments greater than that observed with human polyclonal immunoglobulin G was evident only in one patient. In five patients a slight concentration of both radiopharmaceuticals was reported, due to mild intestinal inflammatory response. These data might be related to mild increase of capillary permeability in the absence of inflammation leukocyte mediated. This study discloses a new cause of IgG-accelerated catabolism due to inflammatory bowel conditions without diarrhea in CVID patients.

Acceleration of Gastric Emptying and Improvement of GERD Outcome After Laparoscopic Sleeve Gastrectomy in Non-diabetic Obese Patients.

Obesity has become a pandemic nowadays. Bariatric surgery is increasingly performed to manage obesity. Currently, laparoscopic sleeve gastrectomy (LSG) is a widely accepted procedure given its feasibility and efficacy. Previous studies revealed conflicting results regarding the change of gastric emptying following sleeve gastrectomy. The primary aim of the present study is to assess gastric motor function by gastric emptying scintigraphy in a cohort of non-diabetic patients undergoing laparoscopic sleeve gastrectomy (LSG) for treatment of severe obesity. This prospective observational study included 100 obese, non-diabetic patients attending the surgery clinic at Cairo University Hospitals and Al Azhar University Hospitals. LSG was performed following a standardized protocol, with no complications observed. All patients had gastric emptying scintigraphy done through a standard semisolid meal (250kcal), marked with 0.5 mCiTc 99, pre-operatively and 3months after LSG. The mean age was 38.71years (9.2) and males comprised 57% of the cohort. The body mass index, low-density lipoproteins, and glycated hemoglobin declined significantly at 3-month postsurgery. The scintigraphy study revealed a significantly reduced percent retention at equivalent time points 3months after LSG. In addition, the percent of patients suffering from GERD decreased significantly after LSG. Gastric emptying becomes faster after LSG in morbidly obese non-diabetic patients. GERD symptoms improve after surgery.

Design and Development of 99mTc-Labeled FAPI Tracers for SPECT Imaging and 188Re Therapy.

Most epithelial tumors recruit fibroblasts and other nonmalignant cells and activate them into cancer-associated fibroblasts. This often leads to overexpression of the membrane serine protease fibroblast-activating protein (FAP). It has already been shown that DOTA-bearing FAP inhibitors (FAPIs) generate high-contrast images with PET/CT scans. Since SPECT is a lower-cost and more widely available alternative to PET, 99mTc-labeled FAPIs represent attractive tracers for imaging applications in a larger number of patients. Furthermore, the chemically homologous nuclide 188Re is available from generators, which allows FAP-targeted endoradiotherapy. Methods: For the preparation of 99mTc-tricarbonyl complexes, a chelator was selected whose carboxylic acids can easily be converted into various derivatives in the finished product, enabling a platform strategy based on the original tracer. The obtained 99mTc complexes were investigated in vitro by binding and competition experiments on FAP-transfected HT-1080 (HT-1080-FAP) or on mouse FAP-expressing (HEK-muFAP) and CD26-expressing (HEKCD26) HEK cells and characterized by planar scintigraphy and organ distribution studies in tumor-bearing mice. Furthermore, a first-in-humans application was done on 2 patients with ovarian and pancreatic cancer, respectively. Results:99mTc-FAPI-19 showed specific binding to recombinant FAP-expressing cells with high affinity. Unfortunately, liver accumulation, biliary excretion, and no tumor uptake were observed on planar scintigraphy for a HT-1080-FAP-xenotransplanted mouse. To improve the pharmacokinetic properties, hydrophilic amino acids were attached to the chelator moiety of the compound. The resulting 99mTc-labeled FAPI tracers revealed excellent binding properties (≤45% binding; >95% internalization), high affinity (half-maximal inhibitory concentration, 6.4-12.7 nM), and significant tumor uptake (≤5.4% injected dose per gram of tissue) in biodistribution studies. The lead candidate 99mTc-FAPI-34 was applied for diagnostic scintigraphy and SPECT of patients with metastasized ovarian and pancreatic cancer for follow-up to therapy with 90Y-FAPI-46. 99mTc-FAPI-34 accumulated in the tumor lesions, as also shown on PET/CT imaging using 68Ga-FAPI-46. Conclusion:99mTc-FAPI-34 represents a powerful tracer for diagnostic scintigraphy, especially when PET imaging is not available. Additionally, the chelator used in this compound allows labeling with the therapeutic nuclide 188Re, which is planned for the near future.

Potential applications of Abelmoschus moschatus polysaccharide as colon release tablets-Rheology and gamma scintigraphic study

In the present scenario of pharmaceutical development, researchers are focusing on the herbal excipients for different delivery systems. This work describes diverse characteristics of novel polysaccharide extracted from the stem of Abelmoschus moschatus (AM). Further, polysaccharide was explored for its potential role as polymer in controlling colon-specific release of metronidazole (MNZ). Cell toxicity study confirmed its safety aspects in biological applications. The aqueous solution of polysaccharide exhibited non-Newtonian pseudoplastic flow property. The consistency coefficient (k) was found to increase with increase in concentration and particle size of AM polysaccharide. Viscosity was found to increase by increasing pH of the aqueous solution of AM. In-vivo gamma scintigraphy study of radiolabeled MNZ tablet in human volunteers confirmed small intestinal transit time of 300–480 min and colon arrival time of 360–480 min. The present study revealed that AM polysaccharide may be a choice of pharmaceutical excipients as an alternative to synthetic polymers.

Esophageal Clearance in Laryngopharyngeal Reflux Disease: Correlation of Reflux Scintigraphy and 24-hour Impedance/pH in a Cohort of Refractory Symptomatic Patients

Objectives:The role of gastroesophageal reflux disease (GERD) in the aetiology of laryngopharyngeal reflux (LPR) is poorly understood and remains a controversial issue. The 24-hour impedance monitoring has shown promise in the evaluation of LPR but is problematic in pharyngeal recording. We have shown the utility of scintigraphic studies in the detection of LPR and lung aspiration of refluxate. Correlative studies were obtained in patients with a strong history of LPR and severe GERD.Methods:A highly selected sequential cohort of patients with a high pre-test probability of LPR/severe GERD who had failed maximal medical therapy were evaluated with 24-hour impedance/pH, manometry and scintigraphic reflux studies.Results:The study group comprised 34 patients (15 M, 19 F) with a mean age of 56 years (range: 28-80 years). The majority had LPR symptoms (mainly cough) in 31 and severe GERD in 3. Impedance bolus clearance and pH studies were abnormal in all patients in the upright and supine position. A high rate of non-acid GERD was detected by impedance monitoring. LOS tone and ineffective oesophageal clearance were found in the majority of patients. Scintigraphic studies showed strong correlations with impedance, pH and manometric abnormalities, with 10 patients showing pulmonary aspiration.Conclusion:Scintigraphic studies appear to be a good screening test for LPR and pulmonary aspiration as there is direct visualisation of tracer at these sites. Impedance studies highlight the importance of non-acidic reflux and bolus clearance in the causation of cough and may allow the development of a risk profile for pulmonary aspiration of refluxate.

Stimuli Responsive In Situ Gelling Systems Loaded with PLGA Nanoparticles of Moxifloxacin Hydrochloride for Effective Treatment of Periodontitis

The objectives of the present research work were systematic development of novel in situ gel formulation containing nanoparticles for localised delivery of moxifloxacin against bacterial periodontitis. PLGA nanoparticles were prepared and optimised in a systematic manner. Factor screening was performed with the help of half-factorial design to identify the influential factors, while response surface optimisation of the nanoparticles was conducted using central composite design. The optimum nanoparticle formulation was chosen on the basis of lower particle size, higher drug entrapment and controlled drug release characteristics up to 1week time period, while the optimum in situ gel was selected on the basis of faster gelling and higher viscosity and gel strength properties for improved retention in the periodontium. In vivo histopathological studies and in vivo gamma scintigraphy studies revealed the extended release, superior efficacy and enhanced retention of nanoparticle-loaded in situ gelling system. Results obtained from in vivo histopathological studies after 1week treatment with in situ gel formulation containing nanoparticles of moxifloxacin were found to be better than with 3weeks treatment of marketed gel formulation. Overall, the studies ratify successful development of an effective site-specific drug delivery system with enhanced biopharmaceutical attributes for the periodontitis treatment.

Sleeve gastrectomy for treatment of delayed gastric emptying-indications, technique, and results.

Delayed gastric emptying (DGE) can be caused by gastric motility disorders such as gastroparesis with idiopathic background, diabetic neuropathy, or postsurgical nerve damage. Currently, a variety of endoscopic and surgical treatment options are available. We noted clinical improvement of gastric emptying with reduction of the gastric fundus following both fundoplication and fundectomy. As a consequence, we explored the effect of sleeve gastrectomy on gastric emptying. The focus of this paper is to investigate the role of laparoscopic sleeve gastrectomy (LSG) in the treatment of gastroparesis. Patients with symptoms suggestive of gastroparesis received diagnostic work-up (gastric emptying scintigraphy and/or Radiographic Barium-Sandwich Emptying studies). Patients with fundic emptying problems and moderate gastric dilation were selected for a LSG. All perioperative parameters were documented regarding patients characteristics, complications, and outcomes expressed as symptoms and quality of life (GIQLI gastrointestinal quality of life index). Assessment of DGE: Barium Emptying Radigraphy Index (BERI) 0-5. From 122 patients with gastroparesis, 19 patients were selected for LSG (mean age 54years (23-68); 10 males/9 females. Morbidity 2/19; no mortality; follow-up mean 24months (12-60); preop/postop: BERI: 2, 31/1, 27 (p < 0.01); we noted significant improvement of the quality of life (preoperative GIQLI 78 (44-89)) to postoperative values of 114 (range 87-120) (p < 0.0001). Preoperative median BMI of these 19 patients was 24 [1-10], which was not significantly changed in the 15 patients at > 1year follow-up with 23 [1-8]. Postoperative recurrence of DGE occurred in 3 patients who were reoperated after >1year follow-up. LSG is a potential surgical treatment option for selected patients with gastroparesis and fundic emptying problems.

Quantifying the effects of absorbed dose from radioembolisation on healthy liver function with [99mTc]TcMebrofenin.

To quantify the effects of absorbed radiation dose on healthy liver parenchyma following radioembolisation (RE) using [99mTc]TcMebrofenin to analyse both global and regional liver function. Patients having RE to treat hepatic disease underwent a [99mTc]TcMebrofenin hepatobilliary scintigraphy (HBS) study at both baseline and 8weeks following treatment. Changes in global liver uptake rate were compared with healthy liver absorbed dose measures derived from the post-treatment 90Y PET/CT, including average dose, minimum dose to 70% of the volume (D70) and volume receiving at least 50Gy (V50). Changes in functional burden associated with treatment and spared liver volumes in patients receiving lobar RE were also assessed, as were changes experienced by regional volumes corresponding to various dose ranges. Standard liver function pathology tests (LFTs) (bilirubin, albumin, ALP, AST, ALT and GGT) were examined for changes between baseline and post-treatment. Thirty-five patients were included in the study, of which, 9 had lobar treatment. A significant linear correlation was found between both baseline global liver uptake rate (negative) and D70 with change in global liver uptake rate. Patients undergoing lobar treatments demonstrated a shift in functional burden, and a significant difference was seen between the mean dose corresponding to liver volumes that increased their functional burden (9Gy) and those that decreased their functional burden (35Gy). No baseline LFTs predicted a decrease in global liver function; however, D70 demonstrated a linear correlation with changes in bilirubin and GGT. Given the significant negative relationship between baseline and change in global liver uptake rate, baseline HBS studies should not be used alone to disqualify patients considered for RE. In terms of treatment planning and evaluation, D70 may be the most appropriate metric of dose, with values greater than 15Gy indicative of a likely drop in global liver function. The evidence of increasing functional burden in spared liver volumes suggests that patients at risk of complications could benefit from a lobar approach to treatment.

Cationic nanoemulsions with prolonged retention time as promising carriers for ophthalmic delivery of tacrolimus

Tacrolimus, also known as FK506, is a first-line drug for the topical treatment of immune-mediated inflammatory anterior ocular diseases (IIAODs). However, due to its limited water solubility, hydrophobic nature and relatively high molecular weight, topical application of FK506 features poor bioavailability. Numbers of formulations have been attempted to enhance the erratic bioavailability of FK506 through various techniques. But until now, none of them could satisfy the clinical needs completely. Here, a novel formulation of FK506, FK506-loaded cationic nanoemulsions (FK506 CNE), was developed to prolong the precorneal residence time of FK506, thereby enhancing the bioavailability of FK506 for IIAODs therapy. FK506 CNE was prepared by high-pressure homogenization, and its composition was screened and optimized by single-factor experiments. The FK506 CNE showed spherical morphology with a mean diameter of 178.8 ± 2.7 nm and a zeta potential of +25.6 ± 0.6 mV. Results from in vivo gamma scintigraphy studies proved that the precorneal residence time of FK506 CNE was significantly increased, compared with FK506-loaded neutral nanoemulsions (FK506 NE) and saline. The data of aqueous humor pharmacokinetic study in rabbits showed that the relative bioavailability of FK506 CNE was 1.68-fold and 1.77-fold of FK506 NE and the marketed FK506 eye drops (Talymus®), respectively. Finally, hematoxylin and eosin staining images and in vitro cytotoxicity data confirmed the safety of the FK506 CNE. Taking all these into consideration, we propose that FK506 CNE is a promising topical ophthalmic nanoformulation for the management of IIAODs.