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Biomedical subjects

James Gibbs

Publications and source records attributed to James Gibbs.

13 recordsLinked to original sources
PubMed2006

CD8 alpha alpha-mediated intraepithelial lymphocyte snatching of thymic leukemia MHC class Ib molecules in vitro and in vivo.

Thymic leukemia (TL) is a MHC class Ib molecule that interacts with CD8alphaalpha homodimers. CD8alphaalpha is abundantly expressed by intraepithelial T lymphocytes (IELs) located in close proximity to TL-expressing intestinal epithelial cells. In this study, we show that CD8alphaalpha(+) IELs "snatch" TL from the plasma membrane of TL-expressing cells and express TL in its proper orientation on their own cell surface. TL snatching is enhanced by cross-linking of IEL TCRs in a phosphatidylinositol kinase-dependent manner, and results in overall alterations to the IEL cell surface detected by enhanced binding of peanut agglutinin lectin. Induction of bowel inflammation results in the presence of TL on IELs, probably via in vivo snatching, providing the initial evidence for the interaction of CD8alphaalpha IELs with intestinal cells.

Animals↗
PubMed2006

Impact of inguinal hernia repair on family and other informal caregivers.

HYPOTHESIS: Inguinal hernia significantly affects family and other informal caregivers, and hernia repair will significantly reduce caregiver burden. METHODS: We analyzed data from a Veterans Affairs Cooperative Study with mixed models to compare the level of burden among caregivers of inguinal hernia patients from preoperative measurement to measurement at 2 weeks and at 3 months postoperatively. RESULTS: Most caregivers were wives (73%) and lived with the patients (88%). There were no differences in caregiver burden by type of treatment. The time caregivers spent assisting patients increased significantly over the 2 weeks following treatment (odds ratio, 4.34). In contrast, 3 months after treatment, caregivers reported spending less time on additional chores than before treatment (odds ratio, 0.12). Furthermore, caregivers' concerns about patients' abilities to perform normal household activities decreased by 2 weeks posttreatment (odds ratio, 0.52). Wives/girlfriends and caregivers of patients with complications were more likely to report these concerns. CONCLUSIONS: Inguinal hernia and its repair significantly affect informal caregivers. Caregivers assumed the heaviest time and effort-related burden 2 weeks following hernia repair and expended additional effort if the patient experienced complications. Interventions should reflect when burden is greatest and target the subgroups of caregivers who most need support.

Adult↗
PubMed2005

Characteristics of NK cell migration early after vaccinia infection.

NK cells are critical components in innate immunity, yet little is known about their migration and proliferation during infection. In this report we study the early NK response toward vaccinia. We observed NK migration into the infected peritoneum as early as 6 h after vaccinia inoculation. Interestingly, although NK trafficking to the infected peritoneum depended on G alpha(i) protein-coupled receptors, trafficking to other tissues (including lung, liver, spleen, and bone marrow) did not. We found that despite a dramatic increase in NK numbers at the primary site of infection, their in situ proliferation was low compared with that at other tissue locations. These features are similar to those found for Ag-experienced T cells, suggesting similar patterns of trafficking and proliferation for these lymphocyte subsets.

Adoptive Transfer↗
PubMed2005

Does surgeon frustration and satisfaction with the operation predict outcomes of open or laparoscopic inguinal hernia repair?

BACKGROUND: A surgeon's level of frustration when performing an operation and level of satisfaction at completion may be correlated with patients' outcomes. We evaluated the relationship between the attending surgeons' frustration and satisfaction and recurrence and complications of open and laparoscopic inguinal hernia repair. STUDY DESIGN: Men with detectable inguinal hernias were randomized to undergo open or laparoscopic herniorrhaphy at 14 Veterans Affairs hospitals. After completion of the procedure, surgeons were asked to assess their level of frustration during the operation and their overall satisfaction with the operative result. Two subjective scales ranging from 1 (not frustrated/not satisfied) to 5 (very frustrated/very satisfied) were used to independently assess both parameters. Reasons for surgeon frustration were evaluated. Patients were followed for 2 years for recurrence and complications. RESULTS: Of 1,983 patients who underwent hernia repair, 1,622 were available for analysis; 808 had open repair and 813 had laparoscopic repair. Surgeons reported less frustration and more satisfaction with open than with laparoscopic repair (p = 0.0001 and 0.0001, respectively). Frustration was associated with a higher rate of hernia recurrence at 2 years (adjusted odds ratio, 2.01, 95% CI, 1.15-3.51) in open repair, and a higher overall rate of postoperative complications (adjusted odds ratio, 1.27, 95% CI, 1.03-1.56) in both open and laparoscopic hernia repair. Satisfaction was not correlated with recurrence or complications. CONCLUSIONS: The level of a surgeon's frustration during performance of an inguinal herniorrhaphy was a better predictor of outcomes of the operation than was satisfaction with the procedure. Sources of intraoperative frustration should be controlled to improve outcomes.

Hernia, Inguinal↗
PubMed2005

Visual analog scales for assessing surgical pain.

BACKGROUND: Four visual analog scales were constructed to assess sensory and affective components of operative pain. The Surgical Pain Scales (SPS) measure pain while at rest, pain during normal activities, pain during work or exercise, and pain unpleasantness. STUDY DESIGN: Longitudinal data from 2,164 patients in a randomized trial of laparoscopic versus open hernia repair established the reliability, validity, and sensitivity to change of the SPS. Correlations and t-tests were used to determine their psychometric properties compared with the SF-36 health status instrument. RESULTS: Intraclass correlation coefficients of 0.95 for the sensory scales and 0.94 for the unpleasantness rating confirmed that the SPS produced reliable measurements. Correlations ranging from 0.44 to 0.60 between the visual analog scales and the bodily pain dimension on the SF-36 and significant differences between SPS levels for patients requiring more and less time to resume normal activities (p< or =0.015 to p< or =0.002) supported the validity of the scales. Clinical responsiveness was demonstrated by a 33.5-mm reduction (standard error = 1.4 mm) in the mean rating on a 150-mm scale measuring pain during normal activities for patients reporting postoperative improvement on the bodily pain dimension (p< or =0.0001). CONCLUSIONS: The Surgical Pain Scales demonstrated excellent psychometric properties in this study population. The SPS can be used to compare pain levels between groups at a single point in time or to track change for individual patients over time or after operations. Individualized pain management interventions can be tailored based on the sensory and effective ratings.

Activities of Daily Living↗
PubMed2005

Assessment of patient functional status after surgery.

BACKGROUND: Improvement in day-to-day functioning is a valued outcome of surgical intervention. A new functional status assessment instrument, the Activities Assessment Scale (AAS), was designed for a randomized clinical trial evaluating laparoscopic versus open hernia repair procedures. STUDY DESIGN: The study data set included 2,164 patients at baseline and 1,562 patients at 3-month followup. Only male patients were enrolled in the trial. The psychometric characteristics of the AAS were examined in statistical analyses of cross-sectional and longitudinal data from the trial. Correlational analyses, factor analyses, and t-tests were used to evaluate scale performance. RESULTS: We found that the AAS was a reliable measure (Cronbach's Coefficient Alpha =0.85) in the patient population studied. Factor analyses identified three subscales (sedentary activities; ambulatory activities; work and exercise activities). Construct validity was demonstrated by a correlation of 0.65 between the AAS and the physical functioning (PF) dimension of the SF-36 (p < 0.001); comparisons between clinical subgroups further confirmed its validity (p < 0.001). Patients reporting improvement on the physical functioning dimension after surgery showed an effect size of 1.20 for preoperative-postoperative change in their AAS scores. CONCLUSIONS: The AAS has been demonstrated to be a reliable, valid, and clinically responsive instrument that can be used to evaluate patient functioning after hernia surgery. It is easy to administer and requires less than 5 minutes of patient time to complete. This measurement system may prove useful in assessing surgical outcomes in both research and office practice settings.

Activities of Daily Living↗
PubMed2004

CD8+ T cell cross-priming via transfer of proteasome substrates.

"Cross-priming" describes the activation of naïve CD8+ T cells by professional antigen-presenting cells that have acquired viral or tumor antigens from "donor" cells. Antigen transfer is believed to be mediated by donor cell-derived molecular chaperones bearing short peptide ligands generated by proteasome degradation of protein antigens. We show here that cross-priming is based on the transfer of proteasome substrates rather than peptides. These findings are potentially important for the rational design of vaccines that elicit CD8+ T cell responses.

Acetylcysteine↗
PubMed2004

Open mesh versus laparoscopic mesh repair of inguinal hernia.

BACKGROUND: Repair of inguinal hernias in men is a common surgical procedure, but the most effective surgical technique is unknown. METHODS: We randomly assigned men with inguinal hernias at 14 Veterans Affairs (VA) medical centers to either open mesh or laparoscopic mesh repair. The primary outcome was recurrence of hernias at two years. Secondary outcomes included complications and patient-centered outcomes. RESULTS: Of the 2164 patients who were randomly assigned to one of the two procedures, 1983 underwent an operation; two-year follow-up was completed in 1696 (85.5 percent). Recurrences were more common in the laparoscopic group (87 of 862 patients [10.1 percent]) than in the open group (41 of 834 patients [4.9 percent]; odds ratio, 2.2; 95 percent confidence interval, 1.5 to 3.2). The rate of complications was higher in the laparoscopic-surgery group than in the open-surgery group (39.0 percent vs. 33.4 percent; adjusted odds ratio, 1.3; 95 percent confidence interval, 1.1 to 1.6). The laparoscopic-surgery group had less pain initially than the open-surgery group on the day of surgery (difference in mean score on a visual-analogue scale, 10.2 mm; 95 percent confidence interval, 4.8 to 15.6) and at two weeks (6.1 mm; 95 percent confidence interval, 1.7 to 10.5) and returned to normal activities one day earlier (adjusted hazard ratio for a shorter time to return to normal activities, 1.2; 95 percent confidence interval, 1.1 to 1.3). In prespecified analyses, there was a significant interaction between the surgical approach (open or laparoscopic) and the type of hernia (primary or recurrent) (P=0.012). Recurrence was significantly more common after laparoscopic repair than after open repair of primary hernias (10.1 percent vs. 4.0 percent), but rates of recurrence after repair of recurrent hernias were similar in the two groups (10.0 percent and 14.1 percent, respectively). CONCLUSIONS: The open technique is superior to the laparoscopic technique for mesh repair of primary hernias.

Hernia, Inguinal↗
PubMed2003

The development of a clinical trial to determine if watchful waiting is an acceptable alternative to routine herniorrhaphy for patients with minimal or no hernia symptoms.

BACKGROUND: This article describes the development and implementation of a randomized clinical trial designed to answer the question: Is watchful waiting an acceptable alternative to operation for men with asymptomatic or minimally symptomatic inguinal hernias? STUDY DESIGN: A clinical trial has been designed to compare watchful waiting and operation for men with an asymptomatic or a relatively asymptomatic inguinal hernia. Men are randomized to watchful waiting or a standard open operation, the Lichtenstein tension-free hernia repair, and are followed for a minimum of 2 years. The target sample size of 753 patients was chosen so that the trial would have power sufficiently high to detect a clinically meaningful difference between treatment groups in either of the two primary outcomes as measured at 2 years: pain or discomfort interfering with normal activities and the physical component summary score of the SF-36 health-related quality-of-life survey. The study was begun in five centers located in both community and academic environments. At 18 months, a sixth site was added and at 28 months, after enrollment of 145 patients, one of the centers was terminated for reasons related to inadequate followup; all data from this center were deleted. As a routine measure, an independent experienced trial manager audited all clinical sites. RESULTS: Enrollment of patients began in January 2000 and will end on December 31, 2002. As of November 1, 2002, 637 patients had been randomized, 85% of the target enrollment. An additional 2,115 patients were screened but not randomized, yielding a recruitment rate of 23.1%. Analysis and publication of the results of the study will take place on completion of the minimum 2-year followup period for all patients. CONCLUSIONS: A trial to compare the outcomes of watchful waiting and operation for management of inguinal hernias in men is needed to provide data to surgeons and to patients that can aid in choice of treatment. A description of the design of such a trial is presented.

Follow-Up Studies↗
PubMed2003

Tension-free inguinal hernia repair: the design of a trial to compare open and laparoscopic surgical techniques.

BACKGROUND: Inguinal hernia is a common condition in men and represents a large component of health-care expenditures. Approximately 700,000 herniorrhaphies are performed each year in the United States. The most effective method of repair of an inguinal hernia is not known. STUDY DESIGN: A multicenter, randomized, clinical trial was designed to compare open tension-free inguinal hernia repair with laparoscopic tension-free repair on recurrence rates, complications, patient-centered outcomes, and cost. The study design called for randomization of 2,200 men over a period of 3 years. These men will be followed for a minimum of 2 years. This will allow determination of as little as a 3% absolute difference in recurrence rates with 80% power. Randomization is stratified by hospital, whether the hernia is unilateral or bilateral and whether the hernia is primary or recurrent. RESULTS: This is a report of the study design and current status. The study involves 14 Veterans Affairs medical centers with previous experience in laparoscopic hernia repair. After 35 months of enrollment, 2,165 men were randomized and recruitment was then closed. The majority of the patients (82.3%) had unilateral hernias and 90.6% of the hernias were primary. Sixty-seven percent of the patients had an outpatient operation. CONCLUSIONS: We report successful recruitment into a large multicenter trial comparing open and laparoscopic hernia repair. When followup is complete, this study will provide data regarding both clinical (recurrence rates) and patient-centered outcomes.

Costs and Cost Analysis↗
PubMed2003

Quantitating protein synthesis, degradation, and endogenous antigen processing.

Using L929 cells, we quantitated the macroeconomics of protein synthesis and degradation and the microeconomics of producing MHC class I associated peptides from viral translation products. To maintain a content of 2.6 x 10(9) proteins, each cell's 6 x 10(6) ribosomes produce 4 x 10(6) proteins min(-1). Each of the cell's 8 x 10(5) proteasomes degrades 2.5 substrates min(-1), creating one MHC class I-peptide complex for each 500-3000 viral translation products degraded. The efficiency of complex formation is similar in dendritic cells and macrophages, which play a critical role in activating T cells in vivo. Proteasomes create antigenic peptides at different efficiencies from two distinct substrate pools: rapidly degraded newly synthesized proteins that clearly represent defective ribosomal products (DRiPs) and a less rapidly degraded pool in which DRiPs may also predominate.

Animals↗
PubMed2002

CD94-NKG2A receptors regulate antiviral CD8(+) T cell responses.

CD8(+) T lymphocytes mediate immunosurveillance against persistent virus infections and virus-induced neoplasia. Polyoma virus, a highly oncogenic natural mouse DNA virus, establishes persistent infection, but only a few mice are highly susceptible to tumors induced by the virus. Mature antiviral CD8(+) T cells expand in tumor-susceptible mice, but their cytotoxic effector activity is nonfunctional in vivo. Here we show that the natural killer cell inhibitory receptor, CD94-NKG2A, is up-regulated by antiviral CD8(+) T cells during acute polyoma infection and is responsible for down-regulating their antigen-specific cytotoxicity during both viral clearance and virus-induced oncogenesis.

Animals↗