Outbreak of lead poisoning from a civilian indoor firing range in the UK.

INTRODUCTION: Lead exposure from discharged lead dust is a recognised risk at firing ranges. We report a lead poisoning outbreak among staff and their close contacts at a UK civilian indoor 24 m firing range. METHODS: A retrospective review was undertaken of data collected on all patients at risk of lead poisoning identified either by direct referral to the Clinical Toxicology clinicians at the West Midlands Poisons Unit, or via the Trace Elements Supra-Regional Assay Service Laboratory at Sandwell hospital. RESULTS: Eighty-seven patients were identified as having possible lead exposure, either at the firing range or via close contacts. Of these, 63 patients aged between 6 months and 78 years attended for blood lead concentration (BLC) testing. The highest BLC at presentation was 11.7 µmol/L (242 µg/dL). Only nine patients reported any symptoms at presentation. Fifteen patients received lead chelation therapy with oral dimercaptosuccinic acid (or succimer) 30 mg/kg/day or intravenous sodium calcium edetate (EDTA) 75 mg/kg/day, dependent on stock availability. DISCUSSION: This report highlights the need for vigilance of lead poisoning as an occupational hazard in the UK, including at recreational facilities such as indoor firing ranges. It emphasises the importance of regulation of lead exposure in the workplace, particularly given the vague symptoms of lead poisoning, and proposes re-appraisal of UK legislation. This report also highlights potential issues surrounding stock availability of rarely used antidotes for uncommon presentations in the event of an outbreak of poisoning.

A Rare Case of Juvenile Polyposis Syndrome Mimicking Ménétrier's Disease.

There is a wide differential diagnosis within polyposis syndromes. Our case represents an interesting and diagnostically challenging diagnosis involving a 41-year-old male who presented with an incidental gastric mass on imaging and a colonic mass seen on colonoscopy. Following multiple endoscopic evaluations, histological analysis, and genetic testing, the patient was ultimately diagnosed with juvenile polyposis syndrome (JPS)/hereditary hemorrhagic telangiectasia (HHT) despite the initial suspicion for Ménétrier's disease. His disease course was complicated by an acute upper extremity thrombus and diagnosis of colorectal carcinoma. This case highlights the importance of a thorough evaluation when polyposis syndromes are suspected. Prompt and accurate diagnosis can aid in the treatment, surveillance, and prevention of colorectal carcinoma.

Gastric Splenosis Mimicking Gastrointestinal Stromal Tumor.

Translocation of splenic tissue in patients after traumatic spleen injury or splenectomy is called splenosis. Gastric splenosis is a rare presentation that can be mistaken for gastrointestinal stromal tumor (GIST). Patients are usually asymptomatic and do not require surgical intervention. In this report, we present a case of a 68-year-old male patient with a previous history of surgical splenectomy after traumatic splenic rupture, who underwent routine upper endoscopy for the evaluation of dysphagia. An endoscopic exam of the stomach revealed an incidental finding of a submucosal gastric nodule. On endoscopic ultrasound exam, the lesion was found to be suggestive of GIST originating from layer 4. A core biopsy was obtained from the nodule, which was consistent with gastric splenosis. The differentiation of gastric splenosis from other gastric lesions such as GIST is important since asymptomatic patients with gastric splenosis do not need to undergo surveillance or surgical resection. It should be suspected especially in patients with a history of splenectomy or splenic rupture. Endoscopic ultrasound (EUS)-guided core biopsy can help confirm the diagnosis and differentiate the condition from GIST.

Novel case of percutaneous access of afferent limb of Roux-en-Y hepaticojejunostomy for biliary decompression and jejunoplasty in a patient with primary sclerosing cholangitis.

Primary sclerosing cholangitis is a rare condition characterized by multifocal fibrotic bile duct strictures and progressive liver disease. Due to its recurrence even after liver transplantation, an alternative surgical procedure, the Roux-en-Y hepaticojejunostomy, is practiced with positive outcomes. We present a case of a 55-year-old female with history of primary sclerosing cholangitis and Roux-en-Y hepaticojejunostomy approximately 25 years ago who presented to the emergency department with acute cholangitis. Computed tomography of the abdomen revealed a dilated loop of small bowel in the right upper quadrant and mid-abdomen with normal bile duct caliber. Interventional radiology was consulted for percutaneous biliary and Roux limb decompression. Ultrasound was utilized to identify and percutaneously access the dilated afferent jejunal limb. With the help of a T-fastener, the jejunal loop was tacked against the anterior abdominal wall and the system was successfully decompressed with a drain left in place. On follow-up, delayed contrast transit through the Roux limb and a stricture in the native jejunum distal to the anastomosis was identified. Hampering of the downstream flow of bile was noted and this was determined to be the likely cause of the initial episode of cholangitis. The strictured bowel segment was balloon-dilated by interventional radiology. Repeat injection of contrast revealed significant improvement in the caliber of the stenotic segment. At 3 weeks' postprocedure, a follow-up enteroscopy of the bowel was performed through the same percutaneous access site. Using this technique, the patient avoided a major invasive surgical procedure.

Triple Assessment of Breast Lump: Should We Perform Core Biopsy for Every Patient?

Introduction The triple assessment for a lump in the breast is standard practice and the robustness of assessment towards the diagnosis of breast cancer is crucial. The combination of the modalities, physical examination, imaging (mammogram and ultrasound), and fine-needle aspiration cytology (FNAC) is more accurate than any modality alone. Aim To examine the combined and individual predictive values of physical examination (P), mammography (M), ultrasound (U), FNAC (C), with core biopsy (B) - triple assessment in the diagnosis of breast cancer. Methods To obtain the results of physical examination (P), mammography (M), ultrasound (U), FNAC (C), and core biopsy (B), we examined the records of 124 breast cancer patients seen between April 1, 2009, and March 30, 2010. To assess the diagnostic potential of the combination of the modalities (P, U, and M), we considered all cases with a score of 4 (probably malignant) and 5 (malignant) as positive for malignancy. All cases with a score of 3 (equivocal), 2 (benign), and 1 (normal) were considered negative for malignancy. For FNAC, a score of 1 (insufficient sample), 2 (benign), and 3 (atypia/probably benign) were considered. All the patients were diagnosed with breast cancer on excision biopsy. Among 124 patients, 12 were excluded, as they were unfit for intervention. Results The accuracy of physical examination (P) as confirmed by core biopsy (B) is dependent on the experience of the surgeon. It has limitations in younger women and smaller lesions. In our study, P has a positive predictive value (PPV) of 58.9% when compared with surgical biopsy, which is comparable with other studies. Our results showed PPV 66.1% and after an ultrasound scan, the overall radiological grading (M & U) gives a PPV of 81.3%, reflecting the important role of ultrasound scans. Our results showed the sensitivity of FNAC to be 73.2%. Core biopsy was diagnostic in 107 (95.5%) patients, making it a reliable tool. Our results confirmed that a combination of the modalities (P, M, U, R, FNAC) is more accurate than any modality alone. Conclusion When all the three modalities are positive for a diagnosis of malignant breast disease, surgical biopsy confirms the breast cancer diagnosis with a PPV of 100% and a sensitivity of 95.5%.

Patient Satisfaction and Understanding of Moderate Sedation During Endoscopy.

Millions of endoscopic procedures are performed in the US every year and the use of procedural sedation analgesia (PSA) is increasing with more procedures being performed outside the operating theater and gaining popularity due to reduced costs. Patients having endoscopic procedures usually expect that they would be deeply sedated during the procedure despite verbal counseling during pre-procedure clinic visits and are often dissatisfied with procedural awareness and discomfort. In order to better educate patients, written supplementary reading material was provided to the patients, which stated a clear goal of comfort during the procedure rather than deep sedation. The results showed that the written supplementary material did not improve the patient's understanding or remembrance of being counseled about moderate sedation. We emphasize that there is no substitute for a physician's repetitive verbal counseling.

Rare Complication of Interventional Radiology-guided Arterial Embolization of the Gastroduodenal Artery in the Setting of Acute Gastrointestinal Bleed: Migrated Coils in the Duodenum.

A 91-year-old male presented to the emergency room with hemodynamically significant upper gastrointestinal bleeding. The patient underwent an esophagogastroduodenoscopy (EGD), which showed frank blood in the duodenum interfering with the visualization. Hence, the patient underwent urgent interventional radiology (IR)-guided arteriogram and embolization. An EGD done 48 hours later showed a giant, non-bleeding, cratered duodenal ulcer with a visible vessel and vascular coils partially protruding into the duodenal bulb lumen. The patient had no evidence of bleeding post embolization. The patient presented three months later with abdominal pain. Computed tomography (CT) abdomen showed multiple liver abscesses. IR-guided drainage of abscesses was performed, and the culture grew Streptococcus intermedius. Magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), and barium enema were unremarkable. The patient was treated with a prolonged course of intravenous (IV) antibiotics and recovered without any further issues. IR guided arterial embolization can be lifesaving in cases where GI bleeding cannot be controlled endoscopically, however, it can lead to serious complications, including endovascular coil migration into the gastrointestinal (GI) lumen causing infection and re-bleeding. Endovascular coil migration can occur immediately or several years later, which can result in fatal bleeding and infection. The best approach to prevent and manage migrated endovascular coils in the GI lumen remains unclear.

Bouveret syndrome as a rare cause of gastric outlet obstruction.

Biliary-enteric fistula is a rare complication of cholelithiasis that can lead to gallstone ileus. Gallstone impaction in the duodenum and pylorus is extremely rare and can lead to gastric outlet obstruction, a condition known as Bouveret syndrome. Bouveret syndrome needs to be diagnosed and managed in a timely fashion, as it has a high mortality rate. We describe a case of an elderly patient who presented with Bouveret syndrome secondary to impaction of the biliary calculus in the first part of duodenum.

Comparison of 'Excision and Primary Repair' with 'Bascom's Technique' in the Surgical Treatment of Pilonidal Sinus.

Introduction The management of the chronic pilonidal disease is variable and the principles of treatment are aimed to eradicate the sinus tract, promote wound healing, prevent disease recurrence, and improve the quality of life of the patient. This study aims to compare the effectiveness of excision and primary closure, and Bascom's technique in the management of pilonidal sinus disease. Methods  The study was performed at a tertiary hospital from April to October 2011. All patients with chronic pilonidal sinus were included in the study (n=60) and randomly allocated into Group A - undergoing excision and primary closure (n=30) and Group B - undergoing Bascom's repair. Comparative outcomes of interest were duration of hospital admission, post-operative pain, wound infection, wound-healing and disease recurrence.  Results The mean age of presentation was 24.18±5.6 years. A higher number of patients in Group A were discharged within 24 hours compared to Group B (p = 0.001). Group B had significantly less post-operative pain by the first postoperative week (p = 0.049). Group B had lower infection rates with clean wounds observed in 28 (93.3%) patients compared to 23 (76.7%) in Group A by the first postoperative week (p = 0.07). Recurrence rate during 12-week follow-up was observed in one (3.3%) patient in Group B, and five (16.7%) in Group A (p= 0.085). Conclusions Patients who underwent Bascom's operation had less postoperative pain, lower infection rates and disease recurrence, and better wound healing. Therefore, in our patient cohort, we conclude Bascom's repair appears to be superior to primary excision and repair in reducing patient morbidity.

Role of Endoscopic Resection Versus Surgical Resection in Management of Malignant Colon Polyps: a National Cancer Database Analysis.

BACKGROUND: Endoscopic resection (polypectomy) or surgery, are the main approaches in management of malignant colon polyps. There are very few large population-based studies comparing outcomes between the two. METHODS: Using the National Cancer Database, we identified patients ≥ 18 years with the first diagnosis of T1N0M0 malignant polyp from 2004 to 2015. Patients with a positive resection margin were excluded. Outcomes were compared between those who had surgery versus those who had polypectomy. Overall survival was compared using Kaplan-Meier curves. Multivariate Cox proportional hazards analysis was performed to generate hazard ratios, adjusted for patient, demographic, and tumor factors. RESULTS: A total of 31,062 patients met the inclusion criteria, out of which 2593 (8.3%) underwent polypectomy alone and 28,469 (91.7%) had surgery. Overall survival was significantly better in the surgical group compared with the polypectomy group. One-year and 5-year survival for surgery were 95.8% and 86.1% respectively compared with 94.2% and 80.6% for polypectomy (p < .0001). Hazard ratio for surgery after adjusting for various clinical-, demographic-, and tumor-level factors was 0.53 (p < .0001). CONCLUSION: Our study is the largest population-based analysis of patients with T1N0M0 malignant colon polyps. Overall survival was higher in patients who underwent surgery compared with polypectomy. This remained consistent even after adjusting for multiple patient and tumor factors between the two groups.

Attitudes and perceptions about prenatal diagnosis and induced abortion among adults of Pakistani population.

OBJECTIVES: Perception and attitude regarding prenatal screening and induced abortion vary across different populations. This study assesses the attitudes and perceptions regarding prenatal screening and induced abortion among Pakistani adults. METHODS: We conducted a cross-sectional study among adults (18+) coming to the Aga Khan University Hospital, a private tertiary care hospital in Karachi, Pakistan. RESULTS: Majority (65%) of the study population had knowledge about prenatal screening and it was acceptable to most (85.5%) of them. Significant proportion had high acceptance for induced abortion (23%) of a fetus that has serious congenital anomalies. On the other hand, 15% were unwilling to consider termination of pregnancy (TOP) in any circumstances. Women had more favorable attitude toward induced abortion. Most of the respondents (63%) were in favor of abortion if fetal death was imminent as a result of a congenital abnormality. Majority wanted mutual consultation of husband and wife for making decision regarding induced abortion (84%). CONCLUSION: There was a considerable discord in opinion about abortion in the study population. Health care providers should involve both parents in making decisions about abortions and counsel them adequately about congenital disorders.

Imaging characteristics of zinc sulfide shell, cadmium telluride core quantum dots.

AIMS: Quantum dots are optical nanocrystals whose in vitro and in vivo use in molecular imaging is expanding rapidly. In comparison with organic fluorophores, quantum dots exhibit desirable properties, such as multiwavelength fluorescence emission, excellent brightness and resistance to photobleaching. Their electron-dense, metallic cores suggest utility in other clinical imaging modalities. METHODS: Core-shell zinc sulfide-cadmium telluride quantum dots were studied by magnetic resonance and computed tomography phantoms. Quantum dots were also injected into rat brain, as well as intravenously, using convection-enhanced delivery, prior to animal imaging. RESULTS: Computed tomography studies suggest that current formulations of quantum dots might be imaged in vivo in animals. CONCLUSIONS: Used in conjunction with optical imaging techniques, quantum dots have the potential to function as multimodal imaging platforms in vivo. The ability to detect an optical nanoparticle preoperatively with clinical imaging modality offers a distinct advantage to clinicians engaged in image-guided surgical applications.

Quantum dots are phagocytized by macrophages and colocalize with experimental gliomas.

OBJECTIVE: The identification of neoplastic tissue within normal brain during biopsy and tumor resection remains a problem in the operative management of gliomas. A variety of nanoparticles are phagocytized by macrophages in vivo. This feature may allow optical nanoparticles, such as quantum dots, to colocalize with brain tumors and serve as an optical aid in the surgical resection or biopsy of brain tumors. METHODS: Male Fisher rats (Charles River Labs, Wilmington, MA) were implanted intracranially with C6 gliosarcoma cell lines to establish tumors. Two weeks after the implantation of tumors, 705-nm emission Qdot ITK Amino(PEG) Quantum Dots (Quantum Dot Corp., Hayward, CA) were injected via the tail vein at doses of 3 to 17 nmol. The animals were sacrificed 24 hours after the injection of quantum dots and their tissues were examined. RESULTS: Quantum dots are avidly phagocytized by macrophages and are taken up by the liver, spleen, and lymph nodes. A dose-response relationship was noted. At low doses, the majority of the quantum dots are sequestered in the liver, spleen, and lymph nodes. At higher doses, increasing quantities of quantum dots are noted within the experimental brain tumors. Macrophages and microglia colocalize with glioma cells, carrying the quantum dot and thereby optically outlining the tumor. Excitation with blue or ultraviolet wavelengths stimulates the quantum dots, which give off a deep red fluorescence detectable with charge-coupled device cameras, optical spectroscopy units, and in dark-field fluorescence microscopy. CONCLUSION: Quantum dots are optical nanoparticles that, when delivered in nanomole doses, are phagocytized by the macrophages and microglia that infiltrate experimental gliomas. The optical signal may be detected, allowing for improved identification and visualization of tumors, potentially augmenting brain tumor biopsy and resection.

Macrophage-mediated colocalization of quantum dots in experimental glioma.

This chapter describes the methodology and a detailed protocol for the targeting and optical imaging of experimental brain tumors in rats using quantum dots (QDs). QDs are optical semiconductor nanocrystals that exhibit stable, bright fluorescence over narrow, size-tunable emission bands. The size-tunable optical properties of QDs allow multiplexing with multiple emission wavelengths from a single excitation source. QDs may be linked to antibodies, peptides, and nucleic acids for use as fluorescence probes in vitro and in vivo. We have hypothesized that the intravenous injection of QDs may represent a novel technique to optically label brain tumors, potentially leading to improved techniques for surgical biopsy and resection.

Compacted DNA nanoparticles administered to the nasal mucosa of cystic fibrosis subjects are safe and demonstrate partial to complete cystic fibrosis transmembrane regulator reconstitution.

A double-blind, dose escalation gene transfer trial was conducted in subjects with cystic fibrosis (CF), among whom placebo (saline) or compacted DNA was superfused onto the inferior turbinate of the right or left nostril. The vector consisted of single molecules of plasmid DNA carrying the cystic fibrosis transmembrane regulator- encoding gene compacted into DNA nanoparticles, using polyethylene glycol-substituted 30-mer lysine peptides. Entry criteria included age greater than 18 years, FEV1 exceeding 50% predicted, and basal nasal potential difference (NPD) isoproterenol responses (> or = -5 mV) that are typical for subjects with classic CF. Twelve subjects were enrolled: 2 in dose level I (DLI) (0.8 mg DNA), 4 in DLII (2.67 mg), and 6 in DLIII (8.0 mg). The primary trial end points were safety and tolerability, and secondary gene transfer end points were assessed. In addition to routine clinical assessments and laboratory tests, subjects were serially evaluated for serum IL-6, complement, and C-reactive protein; nasal washings were taken for cell counts, protein, IL-6, and IL-8; and pulmonary function and hearing tests were performed. No serious adverse events occurred, and no events were attributed to compacted DNA. There was no association of serum or nasal washing inflammatory mediators with administration of compacted DNA. Day 14 vector polymerase chain reaction analysis showed a mean value in DLIII nasal scraping samples of 0.58 copy per cell. Partial to complete NPD isoproterenol responses were observed in eight subjects: one of two in DLI, three of four in DLII, and four of six in DLIII. Corrections persisted for as long as 6 days (1 subject to day 28) after gene transfer. In conclusion, compacted DNA nanoparticles can be safely administered to the nares of CF subjects, with evidence of vector gene transfer and partial NPD correction.

Transfection of airway epithelium by stable PEGylated poly-L-lysine DNA nanoparticles in vivo.

DNA can be compacted using polyethylene glycol-substituted poly-L-lysine into discrete unimolecular (with respect to DNA) nanoparticles with minor diameter < 20 nm that are stable in normal saline for at least 23 months at 4 degrees C. We compared the activity of firefly luciferase in lungs of C57BL/6 mice that received 100 microg compacted plasmid in 25 microl saline (shown to be the optimal dose) via intratracheal or intranasal instillation with levels in animals given 100 microg naked plasmid or in untreated mice. Mice dosed with compacted DNA nanoparticles had peak activity of luciferase in lung at 2 days postinstillation, which declined in log-linear fashion with a half-life of 1.4 days. Luciferase activity in animals dosed with naked DNA was 200-fold less. Addition of polyethylene glycol to the complex was necessary for efficient gene transfer and animals that received DNA compacted with unmodified poly-L-lysine did not exhibit luciferase activity above background. Immunohistochemical staining for bacterial beta-galactosidase 2 days after administration of a compacted lacZ expression plasmid (n = 8) revealed expression predominantly in the dependent portions of the right lungs of mice, in alveolar and airway epithelial cells, though macrophages and sometimes endothelial cells also were transfected. No staining for beta-galactosidase was observed in uninjected animals (n = 4) or those dosed with naked lacZ plasmid (n = 7). Tissue survey for transgene expression shows expression only in lung and trachea following intranasal administration. Stable compacted DNA nanoparticles transfer exogenous genes to airway epithelium and show promise for lung gene therapy.

Minimal toxicity of stabilized compacted DNA nanoparticles in the murine lung.

Nanoparticles containing DNA compacted with poly-l-lysine modified on an N-terminal cysteine with polyethylene glycol can effectively transfect cells of the airway epithelium when applied by the luminal route. To evaluate the toxicity of these nanoparticles, we administered 10 and 100 microg DNA compacted into nanoparticles suspended in normal saline by the intranasal route to mice and determined the pulmonary and systemic responses to this challenge, compared to administration of saline alone, and in some experiments, compared to administration of naked DNA, Escherichia coli genomic DNA, or lipofectin-complexed naked DNA. There was no systemic response to either dose of nanoparticles in serum chemistries, hematologic parameters, serum complement, IL-6, or MIP-2 levels or in the activity, growth, and grooming of the mice. Nanoparticles containing 10 microg DNA induced responses comparable to saline in all measures, including BAL cell counts and differentials and cytokine levels and histology. However, mice dosed with 100 microg DNA in nanoparticles had modest increases in BAL neutrophils 48 and 72 h after dosing, modest increases in BAL IL-6 and KC beginning 24 and 48 h, respectively, after dosing, and, on histology of the lung, a trace to 1+ mononuclear cell infiltrates about the pulmonary veins at 48 h, which were markedly reduced by 10 days and gone by 28 days after dosing. BAL neutrophil and cytokine responses were no greater than those entrained by naked DNA for up to 24 h. However, compared to administration of only 10 microg E. coli genomic DNA, the response to compacted DNA was much less. A low dose of lipofectin-complexed DNA (5 microg DNA) induced the same response as 20-fold higher doses of DNA nanoparticles. These data indicate that DNA nanoparticles have no measurable toxic effect at a dose of 10 microg and a very modest effect, which is not limiting, at a dose of 100 microg, which gives maximal gene expression. This favorable toxicity profile encourages development of stabilized compacted DNA for airway administration.

Nanoparticles of compacted DNA transfect postmitotic cells.

Charge-neutral DNA nanoparticles have been developed in which single molecules of DNA are compacted to their minimal possible size. We speculated that the small size of these DNA nanoparticles may facilitate gene transfer in postmitotic cells, permitting nuclear uptake across the 25-nm nuclear membrane pore. To determine whether DNA nanoparticles can transfect nondividing cells, growth-arrested neuroblastoma and hepatoma cells were transfected with DNA/liposome mixtures encoding luciferase. In both models, growth-arrested cells were robustly transfected by compacted DNA (6,900-360-fold more than naked DNA). To evaluate mechanisms responsible for enhanced transfection, HuH-7 cells were microinjected with naked or compacted plasmids encoding enhanced green fluorescent protein. Cytoplasmic microinjection of DNA nanoparticles generated a approximately 10-fold improvement in transgene expression as compared with naked DNA; this enhancement was reversed by the nuclear pore inhibitor, wheat germ agglutinin. To determine the upper size limit for gene transfer, DNA nanoparticles of various sizes were microinjected into the cytoplasm. A marked decrease in transgene expression was observed as the minor ellipsoidal diameter approached 25 nm. In summary, suitably sized DNA nanoparticles productively transfect growth arrested cells by traversing the nuclear membrane pore.