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Biomedical subjects

J Hart

Publications and source records attributed to J Hart.

At least 19 recordsLinked to original sources

Allelic association of sequence variants in the herpes virus entry mediator-B gene (PVRL2) with the severity of multiple sclerosis.

Discrepant findings have been reported regarding an association of the apolipoprotein E (APOE) gene with the clinical course of multiple sclerosis (MS). To resolve these discrepancies, we examined common sequence variation in six candidate genes residing in a 380-kb genomic region surrounding and including the APOE locus for an association with MS severity. We genotyped at least three polymorphisms in each of six candidate genes in 1,540 Caucasian MS families (729 single-case and multiple-case families from the United States, 811 single-case families from the UK). By applying the quantitative transmission/disequilibrium test to a recently proposed MS severity score, the only statistically significant (P=0.003) association with MS severity was found for an intronic variant in the Herpes Virus Entry Mediator-B Gene PVRL2. Additional genotyping extended the association to a 16.6 kb block spanning intron 1 to intron 2 of the gene. Sequencing of PVRL2 failed to identify variants with an obvious functional role. In conclusion, the analysis of a very large data set suggests that genetic polymorphisms in PVRL2 may influence MS severity and supports the possibility that viral factors may contribute to the clinical course of MS, consistent with previous reports.

3' Untranslated Regions↗

Cognitive function and dissociative disorder status among veteran subjects with chronic posttraumatic stress disorder: a preliminary study.

Twenty-seven veteran subjects with chronic posttraumatic stress disorder (PTSD) were evaluated for dissociative disorders. Ten subjects met criteria for one or more dissociative disorders, and 17 subjects did not meet dissociative disorder criteria. Neurocognitive profiles of the two groups differed in several areas, with veterans meeting diagnostic criteria for both PTSD and a dissociative disorder and demonstrating considerably greater deficits in attention, autobiographical memory, and verbal memory than PTSD subjects without comorbid dissociative disorder diagnosis.

Adult↗

Prevalence of Chlamydia trachomatis in sexual contacts of gonorrhoea.

The British national and local clinic guidelines recommend epidemiological treatment for Chlamydia trachomatis (CT) in patients with gonococcal infection but not their contacts. We aimed to determine the prevalence of CT amongst all gonorrhoea contacts attending over a 30 months period through a retrospective notes review. Of 223 contacts, gonorrhoea was diagnosed in 110 (49.3%) while CT was diagnosed in 54 (24.2%). CT was significantly more prevalent in younger people [(37.8% of contacts <25 years versus 9.6% of contacts >/=25 years (P = 0.000)]. All patients with CT identified as heterosexual except one. Amongst heterosexuals, there was no significant difference in the prevalence between males and females, being 31.6% and 27.8% respectively (P = 0.5995). CT was prevalent in 29.1% of N. gonorrhoeae positive contacts and 19.5% of N. gonorrhoeae negative contacts (p = 0.0935). The high prevalence suggests that epidemiological treatment for CT in gonorrhoea contacts is indicated.

Adult↗

Prospective evaluation of a multi-factorial prevention strategy on the impact of nosocomial infection in very-low-birthweight infants.

The aim of this study was to examine the impact of a multi-factorial intervention on nosocomial infection in very-low-birthweight infants. Consecutive infants with a birth weight less than 1500 g, born between February 2002 and February 2003, were included in this prospective study. The first six-month period (control) included surveillance of current practice. The intervention began in the seventh month and included: (i) changes to handwashing solutions with hand hygiene education; (ii) standardization of intravascular device (IV) insertion with specialized packs; (iii) changes to skin antiseptic solutions (2% aqueous chlorhexidine and 1% chlorhexidine in ethanol); and (iv) mandatory removal or replacement of peripheral IV after 48 hours and removal once enteral intake was > 120 mL/kg/day. Demographic data and details of every device were collected prospectively. Bloodstream infections (BSIs), length of stay (LOS), length of ventilation (LOV) and death were recorded and the rate of nosocomial BSI was calculated. Overall, 174 newborns required 1359 devices. The two cohorts were similar for birth weight and gestation. There was a reduction in nosocomial BSIs from 21% to 9% (control vs. intervention) (P = 0.05, confidence intervals 0.19-1.0). There was no significant difference in LOS, LOV, or mortality. Four infants had complications from 2% chlorhexidine. In conclusion, implementation of the multi-factorial prevention strategy reduced nosocomial BSIs. Alternative antiseptic solutions are needed to reduce the complications caused by 2% aqueous chlorhexidine.

Bacteremia↗

Clinical and economic consequences of volume- or time-dependent intermittent catheterization in patients with spinal cord lesions and neuropathic bladder.

STUDY DESIGN: Open comparative study. OBJECTIVE: To compare the impact of volume-dependent intermittent catheterization (VDIC) and time-dependent intermittent catheterization (TDIC) on financial burden and clinical outcomes in patients with spinal cord lesions (SCL). SETTING: Department of Spinal Rehabilitation, Loewenstein Rehabilitation Hospital, Israel. METHOD: Economic and clinical outcomes were examined in 13 SCL patients treated with VDIC following bladder volume measurement by a portable ultrasound device (the study group), and in 11 patients treated with TDIC (the control group). Patients were followed for 12-30 days. Costs were calculated according to December 2003 prices at Loewenstein Hospital. The t-test and the Fisher's Exact Test were employed for comparisons between the groups. RESULTS: The number of catheterizations per patient per day, the time required to perform volume measurements and catheterizations, and their total cost, were approximately 44, 49, and 46% lower in the study group than in the control group. SCIMU (representing bladder management functioning) increased during the study in both groups, and the increase was 31% higher in the study group than in the control group. Urinary infection was found in three patients in the control group and in none in the study group. CONCLUSION: VDIC has economic and probably also clinical advantages over TDIC.

Adult↗

Comparison of the flow properties of aqueous suspension corticosteroid nasal sprays under differing sampling conditions.

Many aqueous suspension corticosteroid nasal sprays become less viscous when shaken and sprayed, then return to a more viscous state after application. This time-dependent, reversible loss of viscosity under shear (e.g., shaking or spraying) can be quantified in the rheological property of thixotropy. The flow properties of 5 corticosteroid nasal sprays were measured over a range of shear rates. The formulations tested included Nasonex, Vancenase AQ, Nasacort AQ, Rhinocort Aqua, and Flonase. The yield stress values, as well as an estimate of thixotropy, were compared by using three different sampling techniques, including one that simulated patient use (shaking for 30 sec, spraying, and immediately transferring the sample to the rheometer). The rheological properties of all products indicated that when initially shaken and dispensed, they flowed more freely, followed by recovery of viscosity that would likely inhibit the suspensions from flowing out of the nasal cavity. Under all three tested conditions, Nasonex exhibited the highest yield stress, the largest apparent initial and final viscosities, and the highest apparent thixotropy. The study protocol that simulated patient-use conditions produced the following rank order of measured thixotropy: Nasonex > Flonase > Vancenase AQ > Rhinocort Aqua > Nasacort AQ. The thixotropy of Nasonex was 3.4 to 21.4 times greater and the final viscosity was 3.2 to 17.4 times greater than the values of the other tested products.

Administration, Intranasal↗

Expression of NOD2 in Paneth cells: a possible link to Crohn's ileitis.

BACKGROUND AND AIMS: Genetic variation in NOD2 has been associated with susceptibility to Crohn's disease (CD) and specifically with ileal involvement. The reason for the unique association of NOD2 mutations with ileal disease is unclear. To identify a possible link, we tested expression of NOD2 in intestinal tissue of CD patients and controls. PATIENTS AND METHODS: Fifty five specimens of ileum or colon from 21 CD patients, seven ulcerative colitis (UC) patients, and five controls with pathology other than CD or UC were stained for NOD2 using an immunoperoxidase method. RESULTS: Using a monoclonal antibody against NOD2 developed in our laboratory, we detected uniform expression of NOD2 in terminal ileum Paneth cells from controls and patients as well as in metaplastic Paneth cells in the colon. Mechanical purification showed enriched expression of NOD2 mRNA in ileal crypts. In Paneth cells, NOD2 was located in the cytosol in close proximity to the granules that contain antimicrobial peptides. We detected minimal NOD2 in the villous epithelium of the ileum or in the colonic epithelium from both CD patients and controls. CONCLUSIONS: These results suggest a role for NOD2 in the regulation of Paneth cell mediated responses against intestinal bacteria and a plausible mechanism to explain the selective association of NOD2 mutations with ileal disease. The impaired capacity of CD associated mutations to sense luminal bacteria may result in increased susceptibility to certain gut microbes.

Adolescent↗

Interlocking finger test: a bedside screen for parietal lobe dysfunction.

This study sought to determine the utility of an interlocking finger task in screening for parietal lobe dysfunction. The ability of 69 patients to imitate a standardised set of four interlocking finger figures was compared with concurrent performance on formal neurocognitive tests. Poor interlocking finger test scores correlated most highly with standard measures of parietal lobe dysfunction. In addition, an analytical model of parietal dysfunction indicated the interlocking finger test was similar to, if not better than, standard tests of parietal lobe dysfunction. Attempts to imitate these figures should serve as a fast and simple screen of parietal lobe dysfunction.

Adult↗

Randomised, comparative study of three primary dressings for the treatment of venous ulcers.

In this article, we describe a randomised trial in which two established primary dressings - Comfeel (Coloplast, UK) and Granuflex improved formulation (Convatec, UK) - were compared to Cutinova foam (Beiersdorf Medical, UK) in the management of venous leg ulcers. Patients that met the study trial criteria were randomised to receive one of the three primary dressings. All ulcers were secondarily bandaged with Comprilan (Beiersdorf Medical, UK) short-stretch compression. The three dressings were compared in terms of their ability to promote ulcer healing (closure rate and healing rate) and reduce the prevalence and severity of ulcer-associated pain, over a 12-week period. The ease with which dressings could be used in a busy outpatient clinic setting was also considered. On enrollment, groups were well matched in terms of all of the patient and ulcer parameters studies. Six patients were withdrawn for reasons unrelated to study dressings or trial procedures. Following non-parametric analysis of the study data, the three dressings were found to be equally effective at promoting ulcer healing and alleviating ulcer-associated pain. Study personnel rated Cutinova Foam as easy, if not easier, to use than Comfeel or Granuflex. This study suggests that Cutinova Foam is as safe and effective as both Comfeel and Granuflex, in the treatment of venous leg ulcers.

Aged↗

Inflammation. 1: Its role in the healing of acute wounds.

The inflammatory response is an essential part of the wound-healing process. This article discusses inflammation in acute wounds and the part played by the migration of cells including neutrophils, macrophages and T-lymphocytes.

Acute Disease↗

Inflammation. 2: Its role in the healing of chronic wounds.

Why do some wounds fail to heal in the expected time? Part two of this article on inflammation discusses the possible causes, which include recurrence of trauma, bacterial and other contamination and perhaps, above all, the ageing process.

Chronic Disease↗

Electrocorticographic gamma activity during word production in spoken and sign language.

OBJECTIVE: To investigate the functional-neuroanatomic substrates of word production using signed versus spoken language. METHODS: The authors studied single-word processing with varying input and output modalities in a 38-year-old woman with normal hearing and speech who had become proficient in sign language 8 years before developing intractable epilepsy. Subdural electrocorticography (ECoG) was performed during picture naming and word reading (visual inputs) and word repetition (auditory inputs); these tasks were repeated with speech and with sign language responses. Cortical activation was indexed by event-related power augmentation in the 80- to 100-Hz gamma band, and was compared with general principles of functional anatomy and with subject-specific maps of the same or similar tasks using electrical cortical stimulation (ECS). RESULTS: Speech outputs activated tongue regions of the sensorimotor cortex, and sign outputs activated hand regions. In addition, signed word production activated parietal regions that were not activated by spoken word production. Posterior superior temporal gyrus was activated earliest and to the greatest extent during auditory word repetition, and the basal temporal-occipital cortex was activated similarly during naming and reading, reflecting the different modalities of input processing. With few exceptions, topographic patterns of ECoG gamma were consistent with ECS maps of the same or similar language tasks. CONCLUSIONS: Spoken and signed word production activated many of the same cortical regions, particularly those processing auditory and visual inputs; however, they activated different regions of sensorimotor cortex, and signing activated parietal cortex more than did speech. This study illustrates the utility of electrocorticographic gamma for studying the neuroanatomy and processing dynamics of human language.

Brain Mapping↗

Hemispheric asymmetry in categorical versus coordinate visuospatial processing revealed by temporary cortical deactivation.

Kosslyn (1987) proposed that the left hemisphere is better than the right hemisphere at categorical visuospatial processing while the right hemisphere is better than the left hemisphere at coordinate visuospatial processing. In 134 patients, one hemisphere (and then usually the other) was temporarily deactivated by intracarotid injection of sodium amobarbital. After a hemisphere was deactivated, a cognitive test battery was conducted, which included categorical and coordinate visuospatial tasks. Using this technique, the processing capabilities of the intact hemisphere could be determined, thus directly testing Kosslyn's hypothesis regarding hemispheric specialization. Specifically, if the left hemisphere does preferentially process categorical visuospatial relationships, then its deactivation should result in more errors during categorical tasks than right hemisphere deactivation and vise versa for the right hemisphere regarding coordinate tasks. The pattern of results obtained in both categorical and coordinate tasks was consistent with Kosslyn's hypothesis when task difficulty was sufficiently high. However, when task difficulty was low, a left hemispheric processing advantage was found for both types of tasks indicating that: (1) the left hemisphere may be better at "easy" tasks regardless of the type of task and (2) the proposed hemispheric processing asymmetry may only become apparent during sufficiently demanding task conditions. These results may explain why some investigators have failed to find a significant hemispheric processing asymmetry in visuospatial categorical and coordinate tasks.

Adult↗

Cutting edge: membrane lymphotoxin regulates CD8(+) T cell-mediated intestinal allograft rejection.

Blocking the CD28/B7 and/or CD154/CD40 costimulatory pathways promotes long-term allograft survival in many transplant models where CD4(+) T cells are necessary for rejection. When CD8(+) T cells are sufficient to mediate rejection, these approaches fail, resulting in costimulation blockade-resistant rejection. To address this problem we examined the role of lymphotoxin-related molecules in CD8(+) T cell-mediated rejection of murine intestinal allografts. Targeting membrane lymphotoxin by means of a fusion protein, mAb, or genetic mutation inhibited rejection of intestinal allografts by CD8(+) T cells. This effect was associated with decreased monokine induced by IFN-gamma (Mig) and secondary lymphoid chemokine (SLC) gene expression within allografts and spleens respectively. Blocking membrane lymphotoxin did not inhibit rejection mediated by CD4(+) T cells. Combining disruption of membrane lymphotoxin and treatment with CTLA4-Ig inhibited rejection in wild-type mice. These data demonstrate that membrane lymphotoxin is an important regulatory molecule for CD8(+) T cells mediating rejection and suggest a strategy to avoid costimulation blockade-resistant rejection.

Abatacept↗

Risk factors for chronic rejection after pediatric liver transplantation.

BACKGROUND: Chronic rejection is a major cause of graft failure and a frequent reason for retransplantation after pediatric liver transplantation. Identification of risk factors for chronic rejection in pediatric transplant recipients is vital to understanding the pathogenesis of chronic rejection and may help prevent further graft loss. METHODS: The study population consisted of 285 children with 385 liver transplants performed at University of Chicago between 1991 and 1999. Logistic regression analysis was used to evaluate risk factors for chronic rejection, including age, sex, race, type of graft (living related vs. cadaveric), native liver disease, acute rejection episodes, cytomegalovirus (CMV) infection, and posttransplant lymphoproliferative disease (PTLD). RESULTS: The chronic rejection rate was significantly lower in recipients of living-related grafts than in recipients of cadaveric grafts (4% vs. 16%, P=0.001). African-American recipients had a significantly higher rate of chronic rejection than did Caucasian recipients (26% vs. 8%, P<0.001). Numbers of acute rejection episodes, transplantation for autoimmune disease, occurrence of PTLD, and CMV infection were also significant risk factors for chronic rejection. However, recipient age, gender, donor-recipient gender mismatch, and donor-recipient ethnicity mismatch were not associated with higher incidence of chronic rejection CONCLUSION: We have identified a number of risk factors for chronic rejection in a large group of pediatric liver allograft recipients. We believe that donor-recipient matching for gender or race is not likely to reduce the incidence of chronic rejection. The elucidation of the mechanisms by which living-related liver transplantation affords protection against chronic rejection may provide insight into the immunogenetics of chronic rejection and help prevent further graft loss.

Black or African American↗