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1.  PET Imaging of the Effects of Age and Cocaine on the Norepinephrine Transporter in the Human Brain Using (S,S)-[11C]O-Methylreboxetine and HRRT 
Synapse (New York, N.Y.)  2010;64(1):30-38.
The role of the norepinephrine transporter (NET) in cocaine dependence has never been demonstrated via in vivo imaging due to the lack of suitable NET radioligands. Here we report our preliminary studies evaluting the NET in individuals with cocaine dependence (COC) in comparison to healthy controls (HC) using (S,S)-[11C]methylreboxetine ([11C]MRB), the most promising C-11 labeled positron-emission tomography (PET) radioligand for NET developed to date.
Twenty two human volunteers (10 COC and 12 HC) underwent dynamic 11C-MRB-PET acquisition using a High Resolution Research Tomograph (HRRT). Binding potential (BPND) parametric images were computed using the simplified reference tissue model (SRTM2) with occipital cortex as reference region. BPND values were compared between the two groups.
Locus coeruleus (LC), hypothalamus, and pulvinar showed a significant inverse correlation with age among HC (age range = 25–54 years; p = 0.04, 0.009, 0.03 respectively). The BPND was significantly increased in thalamus (27%; p < 0.02) and dorsomedial thalamic nuclei (30%; p < 0.03) in COC as compared to HC. Upon age normalization, the upregulation of NET in COC also reached significance in LC (63%, p < 0.01) and pulvinar (55%, p < 0.02) regions.
Our results suggest that (a) brain NET concentration declines with age in HC, and (b) there is a significant upregulation of NET in thalamus and dorsomedial thalamic nucleus in COC as compared to HC. Our results also suggest that the use of [11C]MRB and HRRT provides an effective strategy for studying alterations of the NET system in humans.
PMCID: PMC3727644  PMID: 19728366
Norepinephrine Transporter; Cocaine abuse; (S,S)-[11C]O-Methylreboxetine; MRB; PET
2.  Pancreatic beta cell mass PET imaging and quantification with [11C]DTBZ and [18F]FP-(+)-DTBZ in rodent models of diabetes 
The aim of this study is to compare the utility of two PET imaging ligands ((+)-[11C]dihydrotetrabenazine ([11C]DTBZ) and the fluoropropyl analogue ([18F]FP-(+)-DTBZ)) that target islet β-cell vesicular monoamine transporter type II (VMAT2) to measure pancreatic β-cell mass (BCM).
[11C]DTBZ, or [18F]FP-(+)-DTBZ was injected, and serial PET images were acquired in rat models of diabetes (streptozotocin-treated and Zucker Diabetic Fatty) and β-cell compensation (Zucker Fatty). Radiotracer standardized uptake values (SUV) were correlated to pancreas insulin content measured biochemically and histomorphometrically.
On a group level, a positive correlation of [11C]DTBZ pancreatic SUV with pancreas insulin content and BCM was observed. In the STZ-diabetic model, both [18F]FP-(+)-DTBZ and [11C]DTBZ correlated positively with BCM, although only ~25% of uptake could be attributed to β-cell uptake. [18F]FP-(+)-DTBZ displacement studies indicate that there is a substantial fraction of specific binding that is not to pancreatic islet β-cells.
PET imaging with [18F]FP-(+)-DTBZ provides a non-invasive means to quantify insulin-positive BCM, and may prove valuable as a diagnostic tool in assessing treatments to maintain or restore BCM.
PMCID: PMC3711476  PMID: 20824509
3.  Kinetic modeling of the serotonin 5-HT1B receptor radioligand [11C]P943 in humans 
[11C]P943 is a new radioligand recently developed to image and quantify serotonin 5-Hydroxytryptamine (5-HT1B) receptors with positron emission tomography (PET). The purpose of this study was to evaluate [11C]P943 for this application in humans, and to determine the most suitable quantification method. Positron emission tomography data and arterial input function measurements were acquired in a cohort of 32 human subjects. Using arterial input functions, compartmental modeling, the Logan graphical analysis, and the multilinear method MA1 were tested. Both the two tissue-compartment model and MA1 provided good fits of the PET data and reliable distribution volume estimates. Using the cerebellum as a reference region, BPND binding potential estimates were computed. [11C]P943 BPND estimates were significantly correlated with in vitro measurements of the density of 5-HT1B receptors, with highest values in the occipital cortex and pallidum. To evaluate noninvasive methods, two- and three-parameter graphical analyses, Simplified Reference Tissue Models (SRTM and SRTM2), and Multilinear Reference Tissue Models (MRTM and MRTM2) were tested. The MRTM2 model provided the best correlation with MA1 binding-potential estimates. Parametric images of the volume of distribution or binding potential of [11C]P943 could be computed using both MA1 and MRTM2. The results show that [11C]P943 provides quantitative measurements of 5-HT1B binding potential.
PMCID: PMC2949107  PMID: 19773803
brain; evaluation of new radiotracers; 5-HT1B serotonin receptors; human; positron emission tomography (PET); tracer kinetic modeling
4.  Femoral Hernia with a Twist 
Case Reports in Medicine  2010;2010:650829.
PMCID: PMC2931410  PMID: 20814561
5.  Occult small bowel perforation in a patient with Ehlers Danlos syndrome: a case report and review of the literature 
Cases Journal  2010;3:57.
Patients who present with a co-existing connective tissue disorder add a degree of complexity to operative intervention. We present an unusual case of a 53-year-old Caucasian female patient with Ehlers Danlos syndrome who presented with an occult perforation of the distal ileum. The patient had known small bowel diverticulae yet the perforation occurred within the normal bowel wall. The pre-operative CT only showed malrotation of the large bowel and did not correlate with the intra-operative findings. Our case has highlighted that although small bowel perforation is a rare occurrence, it may be more common in Ehlers Danlos and may present with atypical features. Perforation may also occur alongside normal bowel as well as diverticulae within the bowel. Where diverticulae exists within a patient with Ehlers Danlos syndrome and there is some diagnostic uncertainty, there should be a lower threshold for operative intervention. We present in the discussion a number of salient features and learning points.
PMCID: PMC2829519  PMID: 20205912
6.  Upper gastrointestinal bleeding due to gastric stromal tumour: a case report 
Cases Journal  2010;3:58.
Gastro-intestinal stromal tumours are the most common mesenchymal tumours of the gastro-intestinal tract. This case report highlights the necessity of early surgical intervention in such cases to avoid mortality due to rebleeding and to raise the awareness of rare causes of upper gastrointestinal bleed and their management.
Case presentation
A 61-year-old male presented to the accident and emergency department with a one-day history of haemetemesis with coffee ground vomiting. After initial resuscitation, he underwent upper gastrointestinal endoscopy under sedation which demonstrated a large, bleeding, gastric mass with a central crater along the greater curvature of the stomach. A partial gastrectomy was performed taking a wedge of the stomach with clearance from the tumour, with no signs of extraperitoneal disease.
Early surgical intervention, either open or laparoscopic resection, is the treatment of choice to prevent rebleeds. In general, complete surgical resection is accomplished in 40-60% of all gastro-intestinal stromal tumours patients, and in >70% of those with primary non- metastatic gastro-intestinal stromal tumour. In our case we had completely excised the tumour. Following surgery, all patients must be referred to centres which have more experience in treating gastro-intestinal stromal tumours. Imatinib is proven to be the first effective systemic therapy in cases of unresectable or metastatic disease. All gastro-intestinal stromal tumours have the potential for aggressive behaviour with the risk being estimated from tumour size and mitotic count.
PMCID: PMC2836292  PMID: 20509859
7.  Small cell carcinoma of the anus: a case report 
Cases Journal  2009;2:9396.
Small cell carcinoma of the anus is a very rare but aggressive tumour. We present a case of a 60-year old lady with small cell carcinoma of the anus. She had no metastatic disease on presentation. She had chemotherapy and radiotherapy but developed distant metastasis after completion of treatment. Immunohistochemistry is required to make a diagnosis. Chemotherapy remains the mainstay of treatment for small cell carcinoma of the anus with or without metastatic disease. Radiotherapy is for local control and relief of symptoms.
PMCID: PMC2806881  PMID: 20076782
8.  Management of an incidentally found large adrenal myelolipoma: a case report 
Cases Journal  2009;2:8414.
Adrenal myelolipoma is a rare benign neoplasm composed of mature adipose and hematopoietic tissue. Most lesions are small, unilateral and asymptomatic, discovered incidentally at autopsy or on imaging studies performed for other reasons. We would like to present a case report of this rare tumour. Cross-sectional imaging is helpful in making a pre-operative diagnosis. The size of the lesion should be a criterion for surgical intervention.
PMCID: PMC2769438  PMID: 19918428
9.  Long-Term Study of Port-Site Incisional Hernia After Laparoscopic Procedures 
Laparoscopic surgery is widely practiced and offers realistic benefits over conventional surgery. There is considerable variation in results between surgeons, concerning port-site complications. The aim of this study was to evaluate the laparoscopic port closure technique and to explore the factors associated with port-site incisional hernia.
Between January 2000 and January 2007, 5541 laparoscopic operations were performed by a single consultant surgeon for different indications. The ports were closed by the classical method using a J-shaped needle after release of pneumoperitoneum. The incidence of port-site incisional hernias was calculated. All patients were followed up by outpatient clinic visits and by their general practitioners.
During a 6-year period, 5541 laparoscopic operations were performed. Eight patients (0.14%) developed port-site hernia during a mean follow-up period of 43 months (range, 25 to 96) and required elective surgery to repair their hernias. No major complications or mortality was reported.
Laparoscopic port closure using the classical method was associated with an acceptable incidence of port-site hernia. Modification of the current methods of closure may lead to a new technique to prevent or reduce the incidence of port-site incisional hernias.
PMCID: PMC3015977  PMID: 19793475
Port-site incisional hernia; Pneumoperitoneum; Port closure
10.  Pneumococcal sepsis presenting as acute compartment syndrome of the lower limbs: a case report 
Acute compartment syndrome is a surgical emergency requiring immediate fasciotomy. Spontaneous onset of acute compartment syndrome of the lower limbs is rare. We present a very rare case of pneumococcal sepsis leading to spontaneous acute compartment syndrome.
Case presentation
A 40-year-old Caucasian man presented as an emergency with spontaneous onset of pain in both legs and signs of compartment syndrome. This was confirmed on fasciotomy. Blood culture grew Streptococcus pneumoniae.
Sepsis should be strongly suspected in bilateral acute compartment syndrome of spontaneous onset.
PMCID: PMC2644321  PMID: 19203372
11.  Management of complications after laparoscopic Nissen's fundoplication: a surgeon's perspective 
Gastro-oesophageal reflux disease (GORD) is a common problem in the Western countries, and the interest in the minimal access surgical approaches to treat GORD is increasing. In this study, we would like to discuss the presentations and management of complications we encountered after Laparoscopic Nissen's fundoplication in our District General NHS Hospital. The aim is to recognise these complications at the earliest stage for effective management to minimise the morbidity and mortality.
301 patients underwent laparoscopic treatment for GORD by a single consultant surgeon in our NHS Trust from September 1999. The data was prospectively collected and entered into a database. The data was retrospectively analysed for presentations for complications and their management.
Surgery was completed laparoscopically in all patients, except in five, where the operation was technically difficult due to pre-existing conditions. The complications we encountered during surgery and follow-up period were major intra-operative bleeding (n = 1, 0.33%), severe post-operative nausea and vomiting (n = 1, 0.33%), wound infection (n = 3, 1%), port-site herniation (n = 1, 0.33%), wrap-migration (n = 2, 0.66%), wrap-ischaemia (n = 1, 0.33%), recurrent regurgitation (n = 4, 1.32%), recurrent heartburn (n = 29, 9.63%), tension pneumothorax (n = 2, 0.66%), surgical emphysema (n = 8, 2.66%), and port-site pain (n = 4, 1.33%).
Minimal access approach to treat GORD has presented with some specific and unique complications. It is important to recognise these complications at the earliest possible stage as some of these patients may present in an acute setting requiring emergency surgery. All members of the department, and not just the members of the specialised team, should be aware about these complications to minimise the morbidity and mortality.
PMCID: PMC2644311  PMID: 19193220
12.  Patient Experience With Gallstone Disease in a National Health Service District Hospital 
The prevalence of gallstone disease in the community makes it an important area of service in district general hospitals. Laparoscopic surgical techniques in synergy with modern imaging and endoscopic and interventional techniques have revolutionized the treatment of gallstone disease, making it possible to provide prompt and definitive care to patients.
Patients with gallstone disease were treated based on a predetermined protocol by a special-interest team depending on the patient's mode of presentation. Data were collected and analyzed prospectively.
Our team treated 1332 patients with gallstone disease between September 1999 and December 2007. Patients (249) with acute symptoms presented through Accident and Emergency (A&E). Despite varied presentations, laparoscopic treatment was possible in all but 8 patients. The study comprised 696 patients who underwent laparoscopic cholecystectomy (LC) as in-hospital (23 hour) cases in a stand-alone center, and 257 outpatients and 379 inpatients. Sixty-seven patients with acute cholecystitis had their surgery within 96 hours of acute presentation. Seventy patients had laparoscopic subtotal cholecystectomy. The overall morbidity was 2.33% with 3 patients having residual common bile duct stones; 3 patients had biliary leak from cystic or accessory duct stumps and one had idiopathic right segmental liver atrophy; 19 had wound infections, 5 had port-site hernia. No mortalities occurred during the 30-day follow-up.
We believe that prompt investigation with imaging and endoscopic intervention if needed along with LC at the earliest safe opportunity by a specialized dedicated team represents an effective method for treating gallstone disease in district general hospitals. Our experience with over 1000 patients has offered us the courage of conviction to say that justice is finally here for gallstone sufferers.
PMCID: PMC3016000  PMID: 19275855
Gallstones; Cholecystectomy; Laparoscopic
13.  An unusual cause of gastric outlet obstruction during percutaneous endogastric feeding: a case report 
The differential diagnoses of acute abdomen in children include common and rare pathologies. Within this list, different types of bezoars causing gastrointestinal obstruction have been reported in the literature and different methods of management have been described. The aim of this article is to highlight a rare presentation of lactobezoars following prolonged percutaneous endoscopic gastrostomy feeding and its successful surgical management.
Case presentation
A 16-year-old boy was admitted to a paediatric ward with abdominal distension and high output from his permanent gastrostomy feeding tube, with drainage of bilious fluids. The clinical, radiological and endoscopical examinations were suggestive of partial duodenal obstruction with multiple bezoars in the stomach and duodenum. Gastrojejunostomy was performed after the removal of 14 bezoars. The child had an uneventful postoperative course and was discharged on the sixth postoperative day in a stable condition.
Lactobezoars should be included in the differential diagnosis of acute abdominal pain in patients with percutaneous endogastric feeding. Endoscopy is important in making the diagnosis of this surgical condition of the upper gastrointestinal tract in a child.
PMCID: PMC2432065  PMID: 18547437
14.  An apricot story: view through a keyhole 
Very few cases of small bowel obstruction due to ingested fruits have been described in literature, and most of these have managed by a laparotomy. Laparoscopic assisted surgery can effectively deal with such impacted foreign bodies, thereby avoiding a formal laparotomy.
Case presentation
A 75 years old lady was admitted via the Accident and Emergency to the surgical ward with a three-day history of abdominal pain and vomiting. Investigations were suggestive of acute small bowel obstruction. On laparoscopy, there was an area of sudden change in calibre of small bowel with dilated proximal and collapsed distal segment in distal jejunum. A foreign body, dried undigested apricot, was extracted by mini-laparotomy.
Small bowel obstruction is a frequent cause of emergency surgery, and aetiology may include food bolus obstruction. Diagnosis is usually confirmed intra-operatively. Foreign body impacted in small bowel can be removed by open or laparoscopic methods.
Generally, laparotomy is performed for diagnosis and management in acute bowel obstruction, but with increasing expertise, laparoscopy can be equally effective with all the other advantages of minimal access approach.
PMCID: PMC1976312  PMID: 17697369
15.  Agenesis of the Gallbladder: Lessons to Learn 
Congenital absence of the gallbladder is a rare, usually asymptomatic, anatomical variation. Some affected individuals may present with a clinical picture suggestive of gallbladder disease. This presentation, coupled with the inability of standard abdominal ultrasonography to convincingly diagnose agenesis of the gallbladder, can put the surgeon in a diagnostic and intraoperative dilemma.
Case Report:
A 30-year-old lady presenting with clinical features of cholecystitis and diagnosed with shrunken gallbladder on ultrasonography was scheduled for laparoscopic cholecystectomy. Intraoperatively, the gallbladder could not be seen even after thorough dissection in the region of the porta hepatis. The procedure was terminated at this stage, and further imaging of the extrahepatic biliary system by magnetic resonance cholangiopancreatography and endoscopic ultrasound confirmed the diagnosis of congenital absence of the gallbladder.
Nonvisualization of the gallbladder at laparoscopy, in the absence of any other diagnosed biliary disorder, need not prompt conversion to open exploration of the extrahepatic biliary system. Newer imaging modalities are relatively noninvasive and can provide good delineation of biliary anatomy. This allows well-planned treatment and at the same time prevents the added morbidity of a diagnostic laparotomy performed solely to confirm the absence of the gallbladder.
PMCID: PMC3015765  PMID: 17575771
Gallbladder; Absence; Congenital; Laparoscopy
16.  Gallstones: Best Served Hot 
Acute episodes of gallstone-related diseases have traditionally been managed conservatively. In the event of gallstones obstructing the common bile duct, patients had endoscopic extraction of calculi with interval cholecystectomy after 4 weeks to 6 weeks when acute inflammatory changes have subsided. This placed the patient at risk of recurrent cholecystitis, pancreatitis, or other complications of cholelithiasis.
Patients presenting with acute gallstone-related diseases were investigated and underwent laparoscopic cholecystectomy during the same admission according to a predetermined treatment protocol.
All patients (119) treated according to the study protocol had good results, with no 30-day mortality and no biliary tract injuries. One patient had bleeding from the cystic artery, and 6 patients required conversion to open cholecystectomy.
Growing expertise in laparoscopic cholecystectomy has made it possible for surgeons to perform safe cholecystectomy in the presence of acute gallstone-related disease. Our experience of managing gallstone disease with prompt cholecystectomy during the index admission shows that this approach provides better, safer, and more cost-effective patient care.
PMCID: PMC3015704  PMID: 17212890
Gallstones; Acute disease; Laparoscopic cholecystectomy

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