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1.  Estimation of effective population size in continuously distributed populations: there goes the neighborhood 
Heredity  2013;111(3):189-199.
Use of genetic methods to estimate effective population size (Ne) is rapidly increasing, but all approaches make simplifying assumptions unlikely to be met in real populations. In particular, all assume a single, unstructured population, and none has been evaluated for use with continuously distributed species. We simulated continuous populations with local mating structure, as envisioned by Wright's concept of neighborhood size (NS), and evaluated performance of a single-sample estimator based on linkage disequilibrium (LD), which provides an estimate of the effective number of parents that produced the sample (Nb). Results illustrate the interacting effects of two phenomena, drift and mixture, that contribute to LD. Samples from areas equal to or smaller than a breeding window produced estimates close to the NS. As the sampling window increased in size to encompass multiple genetic neighborhoods, mixture LD from a two-locus Wahlund effect overwhelmed the reduction in drift LD from incorporating offspring from more parents. As a consequence, never approached the global Ne, even when the geographic scale of sampling was large. Results indicate that caution is needed in applying standard methods for estimating effective size to continuously distributed populations.
PMCID: PMC3746818  PMID: 23652561
genetic monitoring; inbreeding; isolation-by-distance; linkage disequilibrium; wahlund effect; wright's neighborhood
2.  Impact of liver fibrosis on prognosis following liver resection for hepatitis B-associated hepatocellular carcinoma 
British Journal of Cancer  2013;109(3):573-581.
This study aims to evaluate the impact of liver fibrosis severity on prognosis following liver resection among HBV–HCC patients.
Data were extracted from a prospective database of 189 HBV–HCC patients treated at Mount Sinai between 1995 and 2008. Fibrosis staging of each surgical resection specimen using the modified Ishak method was performed by a single liver pathologist.
A wide range of Ishak fibrosis stage was observed among this patient population, with 29% having established cirrhosis (Ishak stage 6). Ishak stage 6 was independently associated with poor overall and recurrence-free survival. In patients with Ishak stage 1–5, Ishak stage did not affect survival; rather, tumour size was associated with poor overall survival, and tumour size, histologic activity index and serum AFP>20 ng ml−1 were associated with poor recurrence-free survival. In patients with Ishak stage 6, poorly differentiated histology and tumour size were associated with poor overall survival, and tumour size was associated with poor recurrence-free survival.
HBV–HCC develops with varying degrees of underlying liver fibrosis; however, progressive liver fibrosis does not affect the outcomes following resection until cirrhosis is reached. Established cirrhosis, as defined histologically by Ishak stage 6, is an independent predictor of poor overall and recurrence-free survival among these patients.
PMCID: PMC3738114  PMID: 23846171
Ishak stage; hepatitis B; hepatocellular carcinoma; prognosis; resection
3.  A Fatal Case of Thallium Toxicity: Challenges in Management 
Journal of Medical Toxicology  2012;9(1):75-78.
Thallium is a highly toxic compound and is occasionally involved in intentional overdoses or criminal poisonings. Accidental poisonings also occur, but are increasingly rare owing to restricted use and availability of thallium. We report a fatal suicidal ingestion of thallium sulfate rodenticide in which multi-dose activated charcoal (MDAC) and Prussian Blue (PB) were both used without changing the outcome.
Case report
A 36 year old man ingested an unknown amount of thallium sulfate grains from an old rodenticide bottle. He presented to an emergency department (ED) 45 minutes later with abdominal pain and vomiting. On examination he was agitated with a blood pressure of 141/60 mmHg and a heart rate of 146 beats per minute (bpm). He received MDAC during his initial ED management and was started on PB 18 hours post arrival; he was intubated on the following day for airway protection. The patient continued to be tachycardic and hypertensive and subsequently developed renal failure. On hospital day three, the patient developed hypotension that did not respond to fluids. The patient required vasopressors and was transferred to a tertiary care center to undergo continuous renal replacement therapy (CRRT). The patient died shortly after his transfer. His last blood thallium concentration was 5369 mcg/L, a spot urine thallium >2000 mcg/L, and a 24- hour urine thallium was >2000 mcg/L.
Though extremely rare, thallium intoxication can be lethal despite early administration of MDAC and use of Prussian blue therapy. Rapid initiation of hemodialysis can be considered in cases of severe thallium poisoning, to remove additional thallium, to correct acid-base disturbance, or to improve renal function.
PMCID: PMC3576490  PMID: 22865288
Thallium; Prussian blue; Multi-Dose activated charcoal; Hemodialysis
Energy homeostasis involves a complex network of hypothalamic and extra-hypothalamic neurons that transduce hormonal, nutrient and neuronal signals into responses that ultimately match caloric intake to energy expenditure and thereby promote stability of body fat stores. Growing evidence suggests that rather than reflecting a failure to regulate caloric intake, common forms of obesity involve fundamental changes to this homeostatic system that favor the defense of an elevated level of body adiposity. This article reviews emerging evidence that during high-fat feeding, obesity pathogenesis involves fundamental alteration of hypothalamic systems that regulate food intake and energy expenditure.
PMCID: PMC3383790  PMID: 21386802
leptin; insulin; inflammation; nutrient; innate immunity; hypothalamus
5.  Ethnic, Racial and Cultural Identity and Perceived Benefits and Barriers Related to Genetic Testing for Breast Cancer among At-Risk Women of African Descent in New York City 
Public Health Genomics  2011;14(6):356-370.
Due to disparities in the use of genetic services, there has been growing interest in examining beliefs and attitudes related to genetic testing for breast and/or ovarian cancer risk among women of African descent. However, to date, few studies have addressed critical cultural variations among this minority group and their influence on such beliefs and attitudes.
We assessed ethnic, racial and cultural identity and examined their relationships with perceived benefits and barriers related to genetic testing for cancer risk in a sample of 160 women of African descent (49% self-identified African American, 39% Black-West Indian/Caribbean, 12% Black-Other) who met genetic risk criteria and were participating in a larger longitudinal study including the opportunity for free genetic counseling and testing in New York City. All participants completed the following previously validated measures: (a) the multi-group ethnic identity measure (including ethnic search and affirmation subscales) and other-group orientation for ethnic identity, (b) centrality to assess racial identity, and (c) Africentrism to measure cultural identity. Perceived benefits and barriers related to genetic testing included: (1) pros/advantages (including family-related pros), (2) cons/disadvantages (including family-related cons, stigma and confidentiality concerns), and (3) concerns about abuses of genetic testing.
In multivariate analyses, several ethnic identity elements showed significant, largely positive relationships to perceived benefits about genetic testing for breast and/or ovarian cancer risk, the exception being ethnic search, which was positively associated with cons/disadvantages, in general, and family-related cons/disadvantages. Racial identity (centrality) showed a significant association with confidentiality concerns. Cultural identity (Africentrism) was not related to perceived benefits and/or barriers.
Ethnic and racial identity may influence perceived benefits and barriers related to genetic testing for breast and/or ovarian cancer risk among at-risk women of African descent. Genetic counseling services may want to take into account these factors in the creation of culturally-appropriate services which best meet the needs of this heterogenous population.
PMCID: PMC3221259  PMID: 21540561
Breast cancer; Cultural identity; Ethnic identity; Genetic testing; Racial identity
6.  Massive Delayed Vaginal Hemorrhage after Laparoscopic Supracervical Hysterectomy 
Background. A known complication of supracervical hysterectomy is cyclical bleeding from the retained cervix when functioning endometrial tissue is not totally removed. We present a rare case of delayed postoperative vaginal hemorrhage after supracervical hysterectomy. Case. A 44-year-old woman presented on postoperative day 15 after laparoscopic supracervical hysterectomy with massive vaginal hemorrhage requiring emergent re-operation. Her bleeding was controlled with vaginally placed sutures. Ultrasound confirmed no intraperitoneal free fluid. The etiology was thought to be induced by postoperative tissue necrosis from cautery applied to the endocervical canal during the original surgery. Conclusion. Delayed vaginal hemorrhage from a retained cervix is a rare complication of laparoscopic supracervical hysterectomy. Caution should be exercised when cauterizing the endocervical canal as induced tissue necrosis may increase the risk of postoperative bleeding.
PMCID: PMC3420099  PMID: 22919525
7.  The role of p21-activated kinase in the initiation of atherosclerosis 
p21-activated kinase (PAK) has been implicated in the inflammatory activation of endothelial cells by disturbed fluid shear stress, which is the initiating stimulus in atherosclerosis. The study addresses whether PAK1 contributes to inflammatory marker expression in endothelial cells at atherosclerosis-susceptible regions of arteries in vivo.
Aortas from WT and PAK1-/- C57BL/6J mice on a normal chow diet were fixed, dissected and processed for immunohistochemistry using a panel of inflammatory markers. We visualized and quantified staining in the endothelium at the greater and lesser curvatures of the arch of aorta, as atherosclerosis-resistant and susceptible regions, respectively.
Fibronectin, VCAM-1 and the activated RelA NF-κB subunit were localized to the lesser curvature and decreased in PAK1-/- mice. The activated RelB NF-κB subunit was also localized to the lesser curvature but was increased in PAK1-/- mice. Low levels of staining for ICAM-1 and the monocyte/macrophage marker Mac2 indicated that overall inflammation in this tissue was minimal.
These data show that PAK1 has a significant pro-inflammatory function at atherosclerosis-prone sites in vivo. These effects are seen in young mice with very low levels of inflammation, suggesting that inflammatory activation of the endothelium is primarily biomechanical. Activation involves NF-κB, expression of leukocyte recruitment receptors and fibronectin deposition. These results support and extend in vitro studies demonstrating that PAK contributes to activation of inflammatory pathways in endothelial cells by fluid shear stress.
PMCID: PMC3489605  PMID: 22824149
Fluid shear stress; Endothelial cells; Vascular inflammation; Fibronectin
8.  Interest in Genetic Testing for Modest Changes in Breast Cancer Risk: Implications for SNP Testing 
Public Health Genomics  2011;14(3):178-189.
Advances in genomics may eventually lead to ‘personalized genetic medicine,’ yet the clinical utility of predictive testing for modest changes in risk is unclear. We explored interest in genetic testing for genes related to modest changes in breast cancer risk in women at moderate to high risk for breast cancer.
Women (n = 105) with a negative breast biopsy and ≥1 relative with breast or ovarian cancer completed telephone surveys. We measured demographic and psychosocial variables and, following presentation of hypothetical scenarios of genetic tests for lower-penetrance breast cancer gene mutations, assessed interest in willingness to pay for and comprehension of test results. We used logistic regression models with generalized estimating equations to evaluate combinations of risk level, cost and behavioral modifiers.
Many women (77%) reported ‘definite’ interest in genetic testing, with greater interest in tests that conveyed more risk and cost less. Behavioral modifiers of risk (taking a vitamin; diet/exercise), having a regular physician, greater perceived benefits of genetic testing, and greater cancer worry also influenced interest. Most participants (63%) did not understand relative vs. absolute risk. Women with less understanding reported more cancer worry and greater willingness to pay for testing.
Interest in genetic testing for mutations related to modest changes in risk was high, modified by both test and psychosocial factors. Findings highlight the need for education about benefits and risks of testing for mutations that convey modest changes in risk, particularly given the current lack of clinical validity/utility and availability of direct-to-consumer genetic testing.
PMCID: PMC3104870  PMID: 21464556
Breast cancer risk; Genetic testing; Interest; Modest risk changes; Public health genomics; Scenario-based research; SNP testing
9.  Gene Synthesis: A Cost-Effective Alternative to Traditional Molecular Cloning 
Gene synthesis is the process of synthesizing a gene in vitro without the need for initial template. Contrary to what many researchers' beliefs, commercial gene synthesis service is quickly evolving to become a cost effective alternative to traditional cloning and other molecular biology procedures. The main reasons include: 1) Time savings: Traditional cloning involves a multi-step process that includes cloning strategy design, primer synthesis, PCR, gel extraction, bacteria transformation, and other complex steps. This process requires considerable amount of time and human resource that gene synthesis does not. 2) Cost savings: In most cases, it costs less to order a synthetic gene than it does to order oligos, cloning kits, and DNA sequencing services. 3) Enhanced DNA performance: Gene synthesis allows for codon optimization which has been proven to increase the efficiency of protein expression. 4) Convenience: Without the need for a physical template and without design restrictions associated with the traditional cloning process, a researcher can get a gene of his/her choice by simply supplying the nucleotide sequence or amino acid sequence. GENEWIZ is a global CRO that provides a wide range of DNA services, including gene synthesis. GENEWIZ's gene synthesis service features a 2-3 week turnaround and expert technical and project management support. This informational poster will present case studies of how GENEWIZ's gene synthesis service benefited researchers who had previously relied on traditional molecular cloning for plasmid construction.
PMCID: PMC3186464
10.  Long-Term Gynecological Outcomes in Women with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency 
Background. Our knowledge on long-term outcome in CAH remains incomplete. Methods. In a prospective study (33 CAH patients, 33 age-matched controls), reproductive outcomes, self-rating of genital appearance and function, and sexuality were correlated to degree of initial virilisation, genotype, and surgery. Results. Patients had larger median clitoral lengths (10.0 mm [range 2–30] versus 3.5 [2–8], P < .001), shorter vaginal length (121 mm [100–155] versus 128 [112–153], P = .12), lower uterine volumes (29.1 ml [7.5–56.7] versus 47.4 [15.9–177.5], P = .009), and higher ovarian volumes (4.4 ml [1.3–10.8] versus 2.8 [0.6–10.8], P = .09) than controls. Satisfaction with genital appearance was lower and negatively correlated to degree of initial virilisation (rs = ≤−0.39, P ≤ .05). More patients had never had intercourse (P = .001), and age at 1st intercourse was higher (18 yrs versus 16 yrs, P = .02). Conclusion. Despite overall acceptable cosmetic results, reproductive outcomes were suboptimal, supporting that multidisciplinary teams should be involved in adult follow up of CAH patients.
PMCID: PMC2963122  PMID: 20981283
11.  Endoscopic gastroplication for the treatment of gastro‐oesophageal reflux disease: a randomised, sham‐controlled trial 
Gut  2006;56(1):20-28.
Endoscopic treatment for gastro‐oesophageal reflux disease (GORD) is rapidly emerging, but there is a great need for randomised controlled trials to evaluate the efficacy.
Design and setting
A single‐centre, double‐blind, randomised, sham‐controlled trial of endoscopic gastroplication by the Endocinch suturing system.
Patients and interventions
60 patients with GORD were randomly assigned to three endoscopic gastroplications (n = 20), a sham procedure (n = 20) or observation (n = 20). The research nurse and patients in the active and sham groups were blinded to the procedure assignment. After 3 months, open‐label active treatment was offered to all patients.
Outcome measures
The primary outcome measures were proton pump inhibitor (PPI) use and GORD symptoms, and secondary measures were quality of life, 24‐h oesophageal acid exposure, oesophageal manometry and adverse events. Follow‐up assessments were performed at 3, 6 and 12 months.
At 3 months, the percentage of patients who had reduced drug use by ⩾50% was greater in the active treatment group (65%) than in the sham (25%) or observation groups (0%) (p<0.02). Symptoms (heartburn and to a lesser extent regurgitation) improved more in the active group than in the sham group. Three Short Form‐20 quality of life subscales (role function, general health and bodily pain perception) improved in the active group versus sham. Oesophageal acid exposure was modestly decreased after active treatment (p<0.02), but not significantly greater than after the sham procedure (p = 0.61). The active treatment effects on PPI use, symptoms and quality of life persisted after 6 and 12 months of open‐label follow‐up (n = 41), but 29% of patients were retreated in this period. No serious adverse events occurred.
Endoscopic gastroplication, using the Endocinch device, reduced acid‐inhibitory drug use, improved GORD symptoms and improved the quality of life at 3 months compared with a sham procedure. The effects persisted up to 12 months. However, the reduction in oesophageal acid exposure was not greater after endoscopic treatment than after a sham procedure.
PMCID: PMC1856666  PMID: 16763053
12.  Tissue specific distribution of the 3243A→G mtDNA mutation 
Journal of Medical Genetics  2006;43(8):671-677.
The 3243A→G is a common pathogenic mitochondrial DNA (mtDNA) point mutation causing a variety of different phenotypes. Segregation of this mutation to different tissues during embryonic life and postnatally is still enigmatic.
To investigate the tissue distribution of this mutation.
In 65 individuals from nine families segregating the 3243A→G mutation, the mutation load (% mutated mtDNA) was determined in various tissues. Mutation load was measured in two to four cell types—blood leucocytes, buccal cells, skeletal muscle cells, and urine epithelial cells (UEC)—derived from all three embryogenic germ layers.
There was a significant correlation among mutation loads in the four tissues (r = 0.80–0.89, p<0.0001). With blood serving as reference, the mutation load was increased by 16% in buccal mucosa, by 31% in UEC, and by 37% in muscle. There were significant differences between the mitotic tissues blood, buccal mucosa, and UEC (p<0.0001), but no difference between UEC and muscle. Using the present data as a cross sectional investigation, a negative correlation of age with the mutation load was found in blood, while the mutation load in muscle did not change with time; 75% of the children presented with higher mutation loads than their mothers in mitotic tissues but not in the post‐mitotic muscle.
There appears to be a uniform distribution of mutant mtDNA throughout the three germ layers in embryogenesis. The significant differences between mutation loads of the individual tissue types indicate tissue specific segregation of the 3243A→G mtDNA later in embryogenesis.
PMCID: PMC2564591  PMID: 16490799
3243A→G; mtDNA; heteroplasmy; mutation distribution; tissue segregation
13.  Patient defined dichotomous end points for remission and clinical improvement in ulcerative colitis 
Gut  2005;54(6):782-788.
Background and aims: Ulcerative colitis disease activity indices offer good statistical power but small changes in these indices may not be clinically important. There are no validated definitions of remission or of significant improvement for these indices. The use of clinically important end points would strengthen the validity of study outcomes. Our aims were to identify objective end points in standard disease activity indices for remission and for improvement in ulcerative colitis.
Methods: Sixty six consecutive patients with ulcerative colitis provided information about remission status and their disease activity. At a return visit 1–14 months later, these patients provided information about the change in their disease activity, and non-invasive indices were measured.
Results: Specific objective end points for determining remission with four standard indices and a quality of life instrument were determined (St Mark’s <3.5, ulcerative colitis disease activity index <2.5, simple clinical colitis activity index (SCCAI) <2.5, Seo <120, and inflammatory bowel disease quality of life index (IBDQ) >205). These cut offs also identified patients who met a regulatory definition of remission. Specific objective end points for clinical improvement in two non-invasive indices and a quality of life instrument were determined with good sensitivity and specificity (SCCAI decrease >1.5, Seo decrease >30, IBDQ increase >20).
Conclusions: We found specific cut off values for disease activity indices that identify patients who have significantly improved or achieved remission in an objective, sensitive, and specific manner. These cut offs should help in the interpretation of the outcomes of clinical trials in ulcerative colitis.
PMCID: PMC1774553  PMID: 15888785
end points; ulcerative colitis; remission; disease activity
14.  A tale of three aspirations: foreign bodies in the airway 
Journal of Clinical Pathology  2003;56(10):791-794.
Tracheobronchial foreign body aspiration is a serious medical problem, with clinical manifestations ranging from acute asphyxiation to insidious lung damage, as demonstrated by the three presented cases. Patient 1 aspirated during dinner, emergency bronchoscopy retrieved pieces of food, and she fully recovered the following day. Patient 2 presented with recurrent pneumonia and a right lower lobe lung abscess. After right lower lobectomy, pathology revealed a foreign object in the right main stem bronchus, a peanut aspirated one year earlier. Patient 3 became unresponsive several days after spinal surgery. The differential diagnosis included myocardial infarction, stroke, and foreign body aspiration. The patient died and necropsy revealed a foreign body in the right main stem bronchus (cooked meat). Thus, foreign body aspiration is not always suspected clinically, and the pathologist may play an important role in making the diagnosis. Histological identification of the aspirated material may be necessary for definitive diagnosis. Therefore, sections of commonly aspirated foods are presented, together with a 10 year history of aspirated objects received by this institution’s surgical pathology department.
PMCID: PMC1770072  PMID: 14514789
aspiration pneumonia; bronchial obstruction; foreign body aspiration
16.  Congenital disorder of glycosylation type Ia (CDG-Ia): phenotypic spectrum of the R141H/F119L genotype 
Archives of Disease in Childhood  2001;85(3):236-239.
AIMS—To delineate common and variable features and outcome of children with congenital disorder of glycosylation type Ia (CDG-Ia) caused by the frequent R141H/F119L PMM2 genotype.
METHODS—Clinical data on 25 patients (mean age 7.6 years, range 0-19) were analysed.
RESULTS—All patients had an early presentation with severe feeding problems and failure to thrive, hypotonia, hepatic dysfunction, inverted nipples, and abnormal subcutaneous fat pads. Eighteen patients were hospitalised in the neonatal period. Developmental delay was obvious before age 6 months. During the first seven months mean standard deviation score (SDS) for weight and length decreased 2.7 (SD = 2) and 2.4 (SD = 2), respectively. Mental retardation, ataxia, muscular atrophy, and febrile seizures were consistent features after infancy. Variable features included pericardial effusions, afebrile seizures, and stroke like episodes. Computed tomography/magnetic resonance imaging of the brain was normal in two patients examined before 4 months of age, but 18children examined after 3 months of age had cerebellar atrophy, and 10 children also had supratentorial atrophy. Subsequent imaging showed progression of the cerebellar and supratentorial atrophy in eight and four of 10 children, respectively. Mean head circumference SDS declined from zero to −1.9 SD from age 3 months to 5 years. Motor ability ranged from none to walking with a rolator, and vocabulary ranged from none to comprehensible speech. The overall mortality ascribed to CDG-Ia was 18%.
CONCLUSION—Patients with the R141H/F119L genotype have an early uniform presentation including severe failure to thrive, but their functional outcome is variable. This genotype may well cause clinical manifestations in the severe end of the spectrum of CDG-Ia.

PMCID: PMC1718926  PMID: 11517108
17.  The UCSC Genome Browser Database 
Nucleic Acids Research  2003;31(1):51-54.
The University of California Santa Cruz (UCSC) Genome Browser Database is an up to date source for genome sequence data integrated with a large collection of related annotations. The database is optimized to support fast interactive performance with the web-based UCSC Genome Browser, a tool built on top of the database for rapid visualization and querying of the data at many levels. The annotations for a given genome are displayed in the browser as a series of tracks aligned with the genomic sequence. Sequence data and annotations may also be viewed in a text-based tabular format or downloaded as tab-delimited flat files. The Genome Browser Database, browsing tools and downloadable data files can all be found on the UCSC Genome Bioinformatics website (, which also contains links to documentation and related technical information.
PMCID: PMC165576  PMID: 12519945
19.  Improving knowledge of the prostate cancer screening dilemma among African American men: an academic-community partnership in Washington, DC. 
Public Health Reports  2001;116(6):590-598.
OBJECTIVE: Studies have shown that African American men are at greater risk than other men for prostate cancer in terms of both incidence and mortality. At the same time, the utility of screening asymptomatic men for prostate cancer remains controversial. The combination of high incidence and high mortality with the uncertain benefits of screening poses a difficult problem for African American men. This study was part of an ongoing project that sought to develop and evaluate health education materials designed to help African American men make an informed decision about prostate cancer screening. The project represented a collaboration between the Most Worshipful Prince Hall Grand Lodge of the District of Columbia and the Lombardi Cancer Center of Georgetown University. METHODS: The authors conducted eight focus groups with 44 members of the Prince Hall Masons. The focus groups covered men's understanding of prostate cancer screening and their preferences for methods of health education. RESULTS: Participants demonstrated a high level of awareness of the availability of prostate cancer screening, a low awareness of the screening controversy, and a desire for detailed epidemiologic information and information about the benefits and limitations of screening. The preferred forms of educational materials were video and print-based materials, which the research team has recently developed. CONCLUSIONS: These findings demonstrate the feasibility of developing an academic-community collaboration with the goal of improving a health-related problem in the African American community. A randomized trial is underway to evaluate the impact of the video and print education materials.
PMCID: PMC1497383  PMID: 12196619
20.  Recurrence of hepatitis C after liver transplantation is associated with increased systemic IL-10 levels. 
Mediators of Inflammation  2001;10(1):37-41.
BACKGROUND: Recurrence of hepatitis C after liver transplantation is an almost universal occurrence. T-cell derived cytokines have an important role in the development of liver damage associated with chronic hepatitis C, their post-transplant levels, however, have not been correlated with histologic recurrence of the disease. AIMS: We sought to analyze levels of TNF-alpha, soluble IL-2 receptor, IL-4 and IL-10 at 1 month, 6 months and 1 year after transplantation in 27 patients undergoing transplantation for hepatitis C related end-stage liver disease. METHODS: HCV RNA levels were monitored by a branched-chain DNA signal amplification assay. Diagnosis of recurrent hepatitis was based on 1-year protocol biopsies and on biopsies performed for liver enzyme elevations. RESULTS: Recurrent hepatitis C was detected in 52% (n=14) of the 27 patients. HCV RNA levels rose over time in all patients regardless of histologic recurrence. TNF-alpha, and IL-4 levels, although elevated, did not show specific patterns over time or in correlation with recurrence. Similarly, the early elevation followed by a gradual decrease over the first year in the amount of soluble IL-2 receptor was not related to histologic recurrence. We observed a significant increase in circulating IL-10 levels over the first year in patients with biopsy-proven recurrence, while patients with no signs of histologic recurrence displayed increased, but steady levels. CONCLUSIONS: These results suggest that while these cytokines are associated with post-transplant recurrence of hepatitis C, their production may be altered by additional factors.
PMCID: PMC1781689  PMID: 11324903
21.  Median nerve injury: an underrecognised complication of brachial artery cardiac catheterisation? 
OBJECTIVE—To describe the local neurological complications associated with cardiac catheterisation via the right brachial artery.
METHODS—A follow up study to determine the mechanism of injury and outcome of patients who sustained a high median nerve palsy after this procedure. Five right handed patients were identified in a 24 month period. Each was assessed clinically and electrophysiologically at presentation. All were followed up initally (range six to 22months) clinically, electrophysiologically, and using components from the Chessington occupational therapy neurological assessment battery (COTNAB) functional hand assessment.
RESULTS—The incidence of this complication was between 0.2 and 1.4%. Three mechanisms of injury were identified. These included direct nerve compression due to formation of antecubital fossa haematoma, direct nerve trauma, and ischaemia secondary to brachial artery occlusion. The initial neurological and nerve conduction deficits improved with time. However, all cases had persistent disability in hand function as documented clinically and on the dexterity and stereognosis subcomponent of the COTNAB test.
CONCLUSION—This is an uncommon, but probably underrecognised complication. Those performing cardiac catheterisation via the right brachial artery should be aware of the potential risks of damage to the median nerve. They should evaluate hand function after the procedure and take prompt action if median nerve dysfunction is noted. Damage to the median nerve results in appreciable long term disability, which may have medicolegal relevance.

PMCID: PMC2169787  PMID: 9343143
23.  Serum folate, homocysteine and colorectal cancer risk in women: a nested case–control study 
British Journal of Cancer  1999;79(11-12):1917-1921.
Accumulating evidence suggests that folate, which is plentiful in vegetables and fruits, may be protective against colorectal cancer. The authors have studied the relationship of baseline levels of serum folate and homocysteine to the subsequent risk of colorectal cancer in a nested case–control study including 105 cases and 523 matched controls from the New York University Women's Health Study cohort. In univariate analyses, the cases had lower serum folate and higher serum homocysteine levels than controls. The difference was more significant for folate (P < 0.001) than for homocysteine (P = 0.04). After ad'justing for potential confounders, the risk of colorectal cancer in the subjects in the highest quartile of serum folate was half that of those in the lowest quartile (odds ratio, OR = 0.52, 95% confidence interval, CI = 0.27–0.97, P-value for trend = 0.04). The OR for the highest quartile of homocysteine, relative to the lowest quartile, was 1.72 (95% CI = 0.83–3.65, P-value for trend = 0.09). In addition, the risk of colorectal cancer was almost twice as high in subjects with below-median serum folate and above-median total alcohol intake compared with those with above-median serum folate and below-median alcohol consumption (OR = 1.99, 95% CI = 0.92–4.29). The potentially protective effects of folate need to be confirmed in clinical trials. © 1999 Cancer Research Campaign
PMCID: PMC2362800  PMID: 10206314
colorectal cancer; folate; homocysteine; cohort study women
24.  Cytokine profiles in early rejection following OKT3 treatment in liver transplant patients. 
Mediators of Inflammation  2000;9(3-4):141-146.
OKT3 , a murine monoclonal antibody specific to the human CD3 complex, induces immunosuppression by depletion of T cells. Administration of OKT3 results in significant release of proinflammatory cytokines, such as TNFalpha and IL1beta. Liver recipients who experience rejection within 3 weeks after transplantation with OKT3 prophylaxis recover their T cells by postoperative day 10 despite complete initial clearance. We sought to analyze the role of proinflammatory and Th-1 cytokines in T cell recovery and rejection after liver transplantation with OKT3 prophylaxis. In plasma samples from 32 patients, we measured TNFalpha, IL1beta and IL6 (before transplant and on postoperative days 1, 2 and 3) and IL2, IFNgamma, sIL2R and slCAM (postoperative days 5, 7 and 10) and examined possible correlations with T-cell recovery and occurrence of rejection within 3 weeks. TNFalpha, IL1beta, and IL6 did not correlate with T-cell recovery. In patients who rejected, IL2 and IFNgamma on postoperative days 5 and 7 correlated with degree of T-cell recovery by day 10; a significant rise in sIL2R over time also correlated with T-cell recovery in this group. Our results emphasize the role of Th-1 cytokines in rejection following OKT3 induction and suggest that markers of T cell activation may predict risk.
PMCID: PMC1781756  PMID: 11132770
25.  Th1/Th2 cytokines and ICAM-1 levels post-liver transplant do not predict early rejection. 
Mediators of Inflammation  2000;9(1):35-38.
Th1 derived cytokines IFN-gamma and IL-2, Th2 cytokine IL-4, and ICAM-1 have been implicated in liver allograft rejection. In order to determine whether monitoring of cytokine profiles during the first days post-liver transplant can predict early rejection we measured IFN-gg, IL-2, sIL-2 receptor, IL-4 and ICAM-1 in 22 patients, in plasma samples obtained within 4 h after liver perfusion (baseline) and between postoperative days (POD) 3-6. ICAM-1 and sIL-2R levels at POD 3-6 were significantly higher than at baseline but did not differ in presence or absence of rejection. Mean percentage increase of ICAM-1 levels was significantly lower in patients with Muromonab-C3 Orthoclone OKT3 (J.C. Health Care) (OKT3) whereas percentage increase of sIL-2R levels was higher in OKT3-treated patients. IFN-gamma levels at POD 3-6 increased from baseline while IL-4 levels were unchanged. Levels of IFN-gamma, IL-4 and their ratios did not correlate with rejection or immunosuppressive therapy. Thus, Th1/Th2 cytokine monitoring during the first week post-transplant does not predict early rejection and immunosuppressive therapy is the predominant factor affecting ICAM and sIL-2R levels after liver transplantation.
PMCID: PMC1781741  PMID: 10877453

Results 1-25 (143)