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1.  Spontaneous pancreatic pseudocyst–portal vein fistula: a rare and potentially life threatening complication of pancreatitis 
Pseudocyst formation following acute and chronic pancreatitis is a well known complication. A pancreatic pseudocyst fistulating into the portal vein is a rare and potentially fatal complication. We report a case of pancreatic pseudocyst – portal vein fistula, which was managed with a conservative approach.
PMCID: PMC3964669  PMID: 23317711
Acute pancreatitis; Pseudocyst; Portal vein; Fistula; Endoscopic retrograde cholangiopancreatography; Puestow procedure
2.  Enhanced frontal function in Parkinson’s disease 
Brain  2009;133(1):225-233.
We investigated the role of dopamine in working memory by examining effects of withdrawing dopaminergic medication in patients with Parkinson’s disease. Resistance to distraction during a delayed response task was abnormally enhanced in Parkinson’s disease patients OFF medication relative to controls. Conversely, performance on a backward digit span test was impaired in these same Parkinson’s disease patients OFF medication. Dopaminergic medication reinstated susceptibility to distraction and backward digit span performance, so that performance of Parkinson’s disease patients ON medication did not differ from that of controls. We hypothesize that the enhanced distractor resistance and impaired backward digit span in Parkinson’s disease reflects low dopamine levels in the striatum, and perhaps upregulated frontal dopamine levels. Dopaminergic medication may reinstate distractibility by normalizing the balance between striatal and prefrontal dopamine transmission.
PMCID: PMC2801327  PMID: 19995871
working memory; cognitive deficits; dopamine; Parkinson’s disease; basal ganglia
3.  Hemodynamics and Bleb Formation in Intracranial Aneurysms 
Background and Purpose
To investigate possible associations between the local hemodynamics and the formation of blebs in cerebral aneurysms.
Computational models of 20 cerebral aneurysms harboring 30 well defined blebs were constructed from 3D rotational angiographies. Models representing the aneurysm before bleb formation were constructed by virtually removing the blebs from the anatomical models. Computational fluid dynamics simulations of the aneurysm before and after bleb formation were performed under pulsatile flows. Flow and wall shear stress (WSS) visualizations were used to analyze the local hemodynamics in the region of the aneurysm that developed the bleb.
Most blebs (80%) occurred at or adjacent to the aneurysm region with the highest WSS before bleb formation, and near the flow impaction zone. Most blebs (83%) were found in regions of the aneurysm previously subjected to high or moderate WSS, and progressed to low WSS states after the blebs were formed. Most blebs (77%) were aligned or adjacent to the inflow jet, while 17% were aligned with the outflow jet, and only 6% were not aligned with the flow direction. Additionally, 90% of the aneurysms had maximum WSS higher than or similar to the WSS in the parent artery.
Blebs form at or adjacent to regions of high WSS and aligned with major intra-aneurysmal flow structures. Formation of blebs results in a lower WSS state with formation of a counter current vortex. These findings imply that locally elevated WSS could contribute to the focalized wall damage that formed these structures.
PMCID: PMC2859623  PMID: 19797790
cerebral aneurysm; blebs; hemodynamics; wall shear stress; computer modeling
4.  Hemodynamic Patterns of Anterior Communicating Artery Aneurysms: A Possible Association with Rupture 
Background and Purpose
The purpose of this study is to characterize the different flow types present at anterior communicating artery aneurysms and investigate possible associations with rupture.
Patient-specific computational models of 26 anterior communicating artery aneurysms were constructed from 3D rotational angiography images. Bilateral images were acquired in 15 patients who had both A1 segments of the anterior cerebral arteries and models of the whole anterior circulation were created by fusing the reconstructed left and right arterial trees. Computational fluid dynamics simulations were performed under pulsatile flow conditions measured on a healthy subject. Visualizations of flow velocity, instantaneous streamlines, and wall shear stress were performed. These were analyzed for flow patterns, size of the impaction zone, and peak wall shear stress (WSS) and then correlations made with prior history of rupture.
Aneurysms with small impaction zones were more likely to have ruptured than those with large impaction zones (83% vs. 63%). Maximum intra-aneurysmal WSS (MWSS) for the unruptured aneurysms ranged from 10 to 230 dyn/cm2 (mean 114 dyn/cm2) compared with ruptured aneurysms from 35–1500 dyn/cm2 (mean 271 dyn/cm2). This difference in MWSS was statistically significant at 90% confidence levels (p=0.10).
Aneurysms with small impaction zones, higher flow rates entering the aneurysm, and elevated maximum wall shear stress are associated with a clinical history of previous rupture.
PMCID: PMC2735769  PMID: 19131411
5.  The safety and tolerability of duloxetine in depressed elderly patients with and without medical comorbidity 
Aim and methods
The impact of medical comorbidity on the efficacy and tolerability of duloxetine in elderly patients with major depressive disorder (MDD) was investigated in this study. Data were obtained from a multicentre, randomised, double-blind, placebo-controlled study in 311 patients with MDD aged 65–89. The primary outcome measure was a prespecified composite cognitive score based on four cognitive tests: (i) Verbal Learning and Recall Test; (ii) Symbol Digit Substitution Test; (iii) 2-Digit Cancellation Test and (iv) Letter-Number Sequencing Test. Secondary measures included the Geriatric Depression Scale (GDS), 17-Item Hamilton Depression Scale (HAMD17), Clinical Global Impression-Severity (CGI-S) Scale, Visual Analogue Scale (VAS) for pain and 36-Item Short Form Health Survey (SF-36). Tolerability measures included adverse events reported as the reason for discontinuation and treatment-emergent adverse events (TEAEs). The consistency of the effect of duloxetine vs. placebo comparing patients with and without medical comorbidity (vascular disease, diabetes, arthritis or any of these) was investigated.
Overall, duloxetine 60 mg/day demonstrated significantly greater improvement compared with placebo for the composite cognitive score, GDS and HAMD17 total scores, CGI-Severity, HAMD17 response and remission rates, and some of the SF-36 and VAS measures. There were few significant treatment-by-comorbidity subgroup interactions for these efficacy variables, or for adverse events reported as the reason for discontinuation and common TEAEs.
The present analyses suggested that the efficacy of duloxetine on cognition and depression in elderly patients, and its tolerability, were not largely affected by the comorbidity status. These results further support the use of duloxetine in elderly patients with MDD.
Dr Wise and Dr Iosifescu have served in consultant/advisory roles for this clinical trial. Dr Iosifescu has received honoraria from Eli Lilly and Company. Neither author has received financial support from Eli Lilly and Company in the form of research funding in the past 2 years. Dr Sheridan has no financial relationship with Eli Lilly and Company. At the time this study was completed, Dr Raskin, Dr Wiltse and Dr Xu were employees of and owned stock in Eli Lilly and Company.
What's knownAnalyses of primary efficacy data from this elderly study have shown that duloxetine 60 mg/day improved cognitive function. Duloxetine 60 mg/day also produced significant improvements vs. placebo in the Geriatric Depression Scale and HAMD17 total scores, as well as some pain measures.What's newThe present report investigates the impact of medical comorbidity on the efficacy of duloxetine in the treatment of depression, improvement of cognition, as well as quality of life and its tolerability in elderly patients with major depressive disorder.
PMCID: PMC2408656  PMID: 17590215
6.  Guidelines for the investigation of chronic diarrhoea, 2nd edition 
Gut  2003;52(Suppl 5):v1-v15.
PMCID: PMC1867765  PMID: 12801941
7.  A prospective randomised multicentre trial comparing 10 Fr Teflon Tannenbaum stents with 10 Fr polyethylene Cotton-Leung stents in patients with malignant common duct strictures 
Gut  2000;46(3):395-400.
BACKGROUND—Stent blockage is a multifactorial process in which stent design and materials, bacteria, proteins, and bile viscosity play a role.
AIMS—To compare the patency of the 10 Fr Teflon Tannenbaum (TT) stent to that of the 10 Fr Cotton-Leung (CL) polyethylene stent with sideholes, in patients with malignant obstructive jaundice.
METHODS—Patients were recruited to this prospective multicentre randomised study if they had a newly diagnosed malignant bile duct stricture below the hilum of the liver suitable for stenting with a 10 Fr stent. Data were collected and monitored by a professional monitoring company. Primary patency was the interval between stent placement and first exchange or death without recurrent jaundice.
RESULTS—134 consecutive patients were recruited between November 1994 and June 1997; 65 were randomised to the TT stent and 69 to the CL stent. Median patency and 95% confidence intervals were 181 (59, 303) days for the TT stent and 133 (92, 174) days for the CL stent, with no significant difference between the two stents (p=0.49). Median survival and 95% confidence intervals were 115 (71, 159) days for the TT stent and 151 (112, 190) days for the CL stent, with no significant difference between the two stents (p=0.765).
CONCLUSION—Neither Teflon as a stent material nor the Tannenbaum design prolong the patency of plastic stents.

Keywords: biliary prosthesis; patency; bile duct malignancy
PMCID: PMC1727856  PMID: 10673303
8.  The predictive value of transabdominal ultrasonography in the diagnosis of biliary tract complications after orthotopic liver transplantation 
Gut  1999;45(6):900-903.
BACKGROUND—In transplant recipients with choledococholedocostomy (CDCD), endoscopic retrograde cholangiopancreatography (ERCP) remains the gold standard for the diagnosis of biliary leak or strictures. Transabdominal ultrasonography (TAUS) has been used to screen patients with suspected biliary tract complications, prior to ERCP, although the clinical effectiveness remains unclear.
AIMS—To assess the predictive value of TAUS in the diagnosis of biliary tract complications after liver transplantation.
METHODS—144 consecutive ERCP and corresponding ultrasonogram reports performed over a 67 month period in 79 patients after liver transplantation were analysed retrospectively.
RESULTS—77 ERCP patients had both a TAUS and a successful ERCP. Biliary tract abnormalities were found at TAUS in 49 (64%) of the 77 patients. TAUS had an overall sensitivity of 77%, and specificity of 67%, with positive and negative predictive values of 26% and 95% respectively, when adjusted for the prevalence rate of biliary complications after liver transplantation of 12.8% in our population. The use of bile duct calibre as sole criterion for an abnormal scan improved the specificity (76%) and with a corresponding reduction in sensitivity (66%). The risk of false negative TAUS was similar in both the early and late post-transplant periods.
CONCLUSIONS—A normal TAUS after liver transplantation with CDCD makes the presence of biliary complications unlikely.

Keywords: endoscopic retrograde cholangiopancreatography; transabdominal ultrasonography; orthotopic liver transplantation; predictive value; sensitivity; specificity
PMCID: PMC1727751  PMID: 10562590
9.  Pretreatment apoptosis in carcinoma of the cervix correlates with changes in tumour oxygenation during radiotherapy 
British Journal of Cancer  2000;82(6):1177-1182.
A relationship between hypoxia and apoptosis has been identified in vitro and in experimental tumours. The aim of this study was to investigate the relationship between apoptosis, hypoxia and the change in oxygenation during radiotherapy in human squamous cell carcinoma of the cervix. Forty-two patients with locally advanced disease underwent pretreatment evaluation of tumour oxygenation using an Eppendorf computerized microneedle electrode. Twenty-two of these patients also had a second evaluation of tumour oxygenation after receiving 40–45 Gy external beam radiotherapy. Paraffin-embedded histological sections were obtained from random pretreatment biopsies for all 42 patients. Apoptotic index (AI) was quantified by morphology on TUNEL stained sections. No correlation was found between pretreatment measures of AI and either the median pO2(r = 0.12, P = 0.44) or percentage of values < 5 mmHg (r = –0.02, P = 0.89). A significant positive correlation was found between AI and the change in tumour oxygenation (ratio of pre:post-treatment % values < 5 mmHg) following radiotherapy (r = 0.61, P = 0.002). The lack of correlation between apoptosis and hypoxia may occur because the Eppendorf measures both acute and chronic hypoxia, and the relative ability of acute hypoxia to induce apoptosis is unknown. These results indicate that cell death via apoptosis may be a mechanism of tumour reoxygenation during radiotherapy. © 2000 Cancer Research Campaign
PMCID: PMC2363353  PMID: 10735502
cervix carcinoma; apoptosis; hypoxia; reoxygenation; radiotherapy
10.  Gut barrier function in malnourished patients 
Gut  1998;42(3):396-401.
Background—The integrity of the gastrointestinal mucosa is a key element in preventing systemic absorption of enteric toxins and bacteria. In the critically ill, breakdown of gut barrier function may fuel sepsis. Malnourished patients have an increased risk of postoperative sepsis; however, the effects of malnutrition on intestinal barrier function in man are unknown. 
Aims—To quantify intestinal barrier function, endotoxin exposure, and the acute phase cytokine response in malnourished patients. 
Patients—Malnourished and well nourished hospitalised patients. 
Methods—Gastrointestinal permeability was measured in malnourished patients and well nourished controls using the lactulose:mannitol test. Endoscopic biopsy specimens were stained and morphological and immunohistochemical features graded. The polymerase chain reaction was used to determine mucosal cytokine expression. The immunoglobulin G antibody response to endotoxin and serum interleukin 6 were measured by enzyme linked immunosorbent assay. 
Results—There was a significant increase in intestinal permeability in the malnourished patients in association with phenotypic and molecular evidence of activation of lamina propria mononuclear cells and enterocytes, and a heightened acute phase response. 
Conclusions—Intestinal barrier function is significantly compromised in malnourished patients, but the clinical significance is unclear. 

Keywords: protein-energy malnutrition; intestinal permeability; endotoxin; cytokine
PMCID: PMC1727047  PMID: 9577348
11.  Avirulence of Candida albicans FAS2 mutants in a mouse model of systemic candidiasis. 
Infection and Immunity  1997;65(2):829-832.
Disruption of both alleles of the Candida albicans FAS2 gene abolishes the ability of the organism to establish infection in a murine model of systemic candidiasis. Within 72 h all mice inoculated with 10(6) CFU of the parental C. albicans strain had died. In contrast, all animals inoculated with the mutant strain CFD2 survived for the course of the experiment (21 days). Animals infected with either mutant strain CFD1 or CFD3, in which only one FAS2 allele was disrupted, also succumbed to infection, but mortality was not observed until 4 days postinfection and survivors remained for up to 20 days postinfection. The results demonstrate that FAS2 is required for successful C. albicans infection.
PMCID: PMC176135  PMID: 9009352
12.  Clonal diversity of Streptococcus mitis biovar 1 isolates from the oral cavity of human neonates. 
The clonal diversity of 101 isolates of the pioneer bacterium Streptococcus mitis biovar 1 obtained from the oral cavities of 40 human neonates 1 to 3 days, 2 weeks, and 1 month postpartum was examined by using rRNA gene restriction patterns. There was a high degree of genetic diversity, with the 101 isolates comprising 93 unique PvuII ribotypes. There were eight identical pairs of ribotype patterns, and seven of the eight pairs were obtained from individual neonates. Only one identical pair comprised isolates obtained from different neonates. In all but two cases, isolates with matching ribotypes were obtained at one visit. Two pairs of isolates with matching ribotype patterns were obtained from neonates on successive visits. The ribotype patterns of the isolates were examined by cluster analysis. The isolates forming each cluster were very similar, yet each cluster was well separated from its neighbors. When several isolates were obtained from individual neonates at a particular visit, in some instances they were contained in a single cluster, whereas in other cases each isolate was contained in a separate cluster. Isolates obtained from individual neonates on successive visits tended to be contained in different clusters. This high degree of diversity, which has been observed in other mucosal commensal bacteria, may serve as a mechanism for avoiding immune elimination of these bacteria.
PMCID: PMC170399  PMID: 8877128
13.  Pioneer oral streptococci produce immunoglobulin A1 protease. 
Infection and Immunity  1994;62(6):2165-2168.
As part of a longitudinal study of the relationship between bacterial colonization and the secretory immune response, 367 isolates of pioneer viridans streptococci collected from 40 breast- and bottle-fed neonates within the first month postpartum were tested for the production of immunoglobulin A1 (IgA1) protease and glycosidases. Fifty percent of the streptococci isolated produced IgA1 protease, including all isolates of Streptococcus oralis and S. sanguis, 60.7% of S. mitis biovar 1 isolates, and some isolates that could not be identified. Three cleavage patterns of alpha 1 heavy chains were observed. Six isolates of S. mitis biovar 1 that did not produce IgA1 protease attacked the alpha 1 chain. Incubation of IgA1 protease-negative S. mitis biovar 1 isolates with IgA1, either prior to or together with S. sanguis, rendered the IgA1 paraprotein resistant to cleavage by the IgA1 protease of S. sanguis. The ability of some pioneer streptococci in the human oral cavity to produce IgA1 protease and of others to modify the susceptibility of IgA1 to cleavage by IgA1 protease perhaps enhances their ability to survive in this habitat.
PMCID: PMC186493  PMID: 8188337
14.  Natural transmission of Streptococcus sobrinus in rats: saliva and serum antibody responses to colonization. 
Infection and Immunity  1992;60(3):778-783.
One hundred and twenty weanling rats fed diet NIH 2000 that were free of Streptococcus sobrinus and other mutans streptococci were employed in this study. Sixty rats were inoculated orally with S. sobrinus 6715. Each infected rat (donor) was paired and housed with an uninfected recipient. Saliva and serum samples were collected from 24 (12 donor and 12 recipient) rats at the baseline (day 0) and from groups of 12 recipients sacrificed on days 10, 24, 38, and 52, and the level of infection with S. sobrinus was monitored. Salivary immunoglobulin A (IgA) and IgG and serum IgM and IgG antibodies reactive with whole cells (WC), glucosyltransferase (GTF), and the serotype carbohydrate (g) of S. sobrinus were measured by an indirect enzyme-linked immunosorbent assay. Although the rats were free of S. sobrinus and other mutans streptococci at baseline, they exhibited salivary IgA and serum IgM antibodies reactive with S. sobrinus WC, GTF, and g and serum IgG antibodies reactive with WC and GTF. Infection of recipients with S. sobrinus did not induce salivary antibodies reactive with WC, GTF, or g. In contrast, increases in serum IgM and IgG antibodies reactive with WC and serum IgM antibodies reactive with g were observed.
PMCID: PMC257554  PMID: 1531814
15.  Speech defects in children. 
British Medical Journal  1973;2(5869):780-781.
PMCID: PMC1589776  PMID: 4718339
16.  Sheridan-Gardiner test for visual acuity. 
British Medical Journal  1970;2(5701):108-109.
PMCID: PMC1699941  PMID: 4246194
19.  Hepatic Necrosis Due to Marsilid 
Gut  1960;1(2):169-170.
In the patient reported here severe jaundice and death resulted from treatment with iproniazide (“marsilid”) given for only three days.
PMCID: PMC1413210  PMID: 18668732
21.  Antral Infection in Children 
British Medical Journal  1948;1(4540):74-75.
PMCID: PMC2089669  PMID: 18932754
23.  Chronic Suppurative Otitis Media 
British Medical Journal  1936;1(3928):791-792.
PMCID: PMC2458633  PMID: 20779844

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