Improved quality of life following total pancreatectomy and auto-islet transplantation for chronic pancreatitis.

BACKGROUND: Total pancreatectomy (TP) with auto-islet transplant (AIT) is an extreme treatment for chronic pancreatitis, and we reviewed our experience to assess the impact on quality of life (QOL). METHODS: A prospective cohort study from 2007 through 2010 with pre- and postoperative assessments of the Depression Anxiety Stress Scale, Pain Disability Index, and visual analogue pain scale was performed. RESULTS: Twenty patients underwent TP-AIT with a median follow-up of 12 months (6.75-24 months). All patients reported moderate (45 %) to severe (55 %) pain prior to surgery. TP-AIT resulted in significant decreases in abdominal pain (p < 0.001), 80 % reporting no or mild pain. Despite pain improvement, only 30 % discontinued narcotics. Improvements in all PDI QOL domains improved from 79 to 90 % (p = 0.002), with greatest improvements seen in those without prior pancreatic surgery, younger patients, and in those with higher levels of preoperative pain. Patients were less affected by depression and anxiety prior to surgery, but 60 and 70 % did show improvement in depression and anxiety, respectively (p = 0.033). Sixteen patients (80 %) required exogenous insulin at last follow-up (mean total dose of insulin 11.6 U/day). CONCLUSIONS: TP-AIT significantly improves pain and QOL measures in appropriately selected patients with CP.

Lifetime risk of surgical management for pelvic organ prolapse or urinary incontinence.

The objective of our study was to estimate the age-specific incidence and lifetime risk of surgically managed pelvic organ prolapse (POP) and urinary incontinence (UI). Women aged 20 and older who underwent primary surgical management of POP or UI in 1993 were identified from the database of a health maintenance organization using ICD-9 codes and confirmed through chart abstraction. From a population of 147,719 women, 135 were identified who underwent prolapse surgery only, 82 incontinence only, and 34 surgery for both conditions. From the age-specific incidence, we estimated the lifetime risk of undergoing an operation by age 80 to be 11.8%. Our findings agree with a previous estimate that approximately 11% of women will undergo surgery for POP or UI by age 80. POP and UI appear to be common problems, undoubtedly affecting an even larger proportion of the women than suggested by this high cumulative incidence of surgery.

The functional and psychosocial impact of fecal incontinence on women with urinary incontinence.

OBJECTIVES: The study was undertaken to determine the impact of fecal incontinence (FI) on functional status and quality of life in women with urinary incontinence (UI). STUDY DESIGN: In 24 months 732 women completed a standardized assessment and questionnaire, including the Short Form (SF)-12 and Incontinence Quality of Life (I-QOL) scores. Analysis of variance was used to compare SF-12 scores between groups defined as having UI, FI, or both UI and FI. I-QOL scores in patients with UI or UI and FI were compared by using the Student t test. RESULTS: Of the 732 patients enrolled, 425 patients had either UI (n = 342, 80%), FI (n = 18, 4%), or both (n = 65, 15%). Greater impairment in physical functioning was seen in the group with UI and FI (38.6; P =.027) compared with the group with UI (42.4). Significant decreases in I-QOL scores were seen for the group with UI and FI compared with those with UI (P <.005). CONCLUSION: Fecal incontinence further reduces the functional status and quality of life of women with urinary incontinence.

Development of a bench station objective structured assessment of technical skills.

OBJECTIVE: We have previously shown that objective structured assessment of technical skills performed in an animal model was an innovative, reliable, and valid method of assessing surgical skills. Our goal was to develop a less costly bench station objective structured assessment of technical skills and to evaluate the feasibility, reliability, and validity of this exam. METHODS: A seven-station examination was administered to 24 residents. The tests included laparoscopic procedures (salpingostomy, intracorporeal knot tying, closure of port sites) and open abdominal procedures (subcuticular closure, bladder neck suspension, repair of enterotomy, abdominal wall closure). All tasks were performed using life-like surgical models. Residents were timed and assessed at each station using three methods of scoring: a task-specific checklist, a global rating scale, and a pass/fail grade. RESULTS: Assessment of construct validity, the ability of the test to discriminate among residency levels, found significant differences on the checklist, global rating scale, time for procedures, and pass/fail grade by level of training. Reliability indices calculated with Cronbach's alpha were 0.77 for the checklists and 0.94 for the global rating scale. Overall interrater reliability indices were 0.91 for the global rating scale and 0.92 for the checklists. Total cost for replaceable parts and facilities was $1900. CONCLUSION: The less costly and more portable bench station objective structured assessment of technical skills can reliably and validly assess the surgical skills of gynecology residents. This type of examination can be a useful tool to identify residents who need additional surgical instruction, provide remediation, and may become a mechanism to certify surgical skill competence.

Testing surgical skills of obstetric and gynecologic residents in a bench laboratory setting: validity and reliability.

OBJECTIVE: Resident surgical skills are acquired mainly through observing and later performing procedures in the operating room. Evaluation of surgical skills has traditionally been done through subjective faculty evaluation, a technique that has poor reliability and unknown validity. Our goal was to develop specific surgical tasks, both laparoscopic and open abdominal, that could be objectively and reliably evaluated in a bench laboratory setting. STUDY DESIGN: The prospective development of a reliable and valid resident surgical skills test in a bench laboratory setting was our goal. A written test of surgical knowledge and 12 skills tests were administered to 36 residents. Laparoscopic bench tasks were simulated with the use of a box and camera with a video display. Six laparoscopic tasks were assessed, including placing pegs on a board, running the bowel simulation, and other tasks that involve hand-eye coordination and manual dexterity. Open abdominal skills simulated incision closure, suturing a vaginal cuff, knot tying, and using a tie on a passer. Residents were timed at each given station and were given a rating score by 2 examiners. RESULTS: Knowledge scores showed a significant improvement by residency level. Assessment of construct validity (the ability to discriminate among residency levels) demonstrated significant differences on the rating of overall performance and individual tasks by level (determined by 1-way analysis of variance). Interrater reliability (agreement between 2 raters) with the use of intraclass correlation was 0.79 for the total score. The cost to administer the bench laboratory test was less than $50 and required 30 hours of faculty time. CONCLUSION: The results of this study suggest that surgical bench laboratory tasks can assess residents' surgical skills with good reliability and validity on most tasks. Our previous study, which used an animal laboratory, was expensive, and the bench laboratory model may provide an alternative means to assess surgical skills.

The second stage of labor and stress urinary incontinence.

OBJECTIVE: This study was undertaken to investigate the potential association between prolonged second stage of labor and stress urinary incontinence. STUDY DESIGN: A retrospective, population-based study was performed. A random, case-controlled sample of 85 cases and 88 controls was identified by means of a standard computerized patient database. Subjects were identified by International Classification of Diseases, Ninth Revision codes, and medical records were reviewed. The median follow-up time from delivery was 7.8 years for cases and 7.2 years for controls. Multiple logistic regression was performed to test for an association between stress urinary incontinence and variables of interest. RESULTS: The data suggest that for all women who labored the length of the second stage of labor for the first delivery was not associated with stress urinary incontinence (odds ratio, 1.07; P =.42; 95% confidence interval, 0.9-1.3). However, forceps delivery was associated with a significant increase in stress urinary incontinence risk (odds ratio, 10.4; P =.04; 95% confidence interval, 1.2-93.4). CONCLUSION: Length of second stage of labor was not associated with stress urinary incontinence. However, the odds of having a later diagnosis of stress urinary incontinence was 10 times higher for women who underwent forceps delivery.

Development of an objective structured assessment of technical skills for obstetric and gynecology residents.

OBJECTIVE: To develop an objective structured assessment for evaluating surgical skills of obstetrics and gynecology residents and to evaluate the reliability and validity of the assessment. METHODS: A seven-station, objective, structured assessment of technical skills was administered to 24 residents. The test included laparoscopic procedures (port placement, salpingostomy, suturing, vessel ligation) and open abdominal procedures (hypogastric ligation, repair of enterotomy, salpingo-oophorectomy.) All surgical tasks were done on pigs. Residents were timed and assessed at each station using three methods of scoring, a task-specific checklist, global rating scale, and pass-fail grade. RESULTS: Assessment of construct validity (the ability of the test to discriminate among residency levels) found significant differences on the checklist and the global rating scale by residency level. Reliability indices calculated with Cronbach's alpha were 0.89 for the global rating scale and 0.89-0.95 for the individual skills checklists. Interrater reliability was 0.87 for the global rating scale and 0.78-0.98 for the checklists. CONCLUSION: Objective, structured assessment of technical skills can assess residents' surgical skills with high reliability and validity. These assessments have possible application for identifying residents who need additional training and might provide a mechanism to ensure competence of surgical skills.

Teaching and evaluating surgical skills.

OBJECTIVE: To examine how surgical skills are taught and evaluated in obstetrics-gynecology residency programs in the United States. METHODS: A questionnaire was mailed to the directors of all 266 residency programs in the United States and to second contact names at 51 sites. Directors were asked to evaluate how surgical skills are taught and evaluated and to rate the importance of specific techniques and procedures for residents at given points in resident training. RESULTS: Two hundred twenty-three surveys were returned (70%), representing 203 of 266 programs (76%). Among responding programs, 99% reported teaching surgical skills in operating rooms, 88% in lectures, 68% with bench procedures, and 54% with animal surgery. Twenty-nine percent indicated they had formal surgical skills curricula. A significantly higher percentage of those programs with formal curricula used animal surgery laboratories (81% versus 42%, P <.001) and were more likely to conduct formal skills assessments (88% versus 69%, P =.005) than programs without formal curricula. Overall, 74% of programs evaluated surgical skills. Of those, 56% reported using subjective faculty evaluations, 12% written evaluations (eg, checklists), 4% written and oral assessments, and 1% a test. Regardless of formal curricula, there was much agreement in respondents' ratings of 60 different skills and procedures as "essential," "important," "nice to know," or "unimportant. CONCLUSION: Most programs teach surgical skills in the operating room and through lectures. Only 29% of reporting programs provide formal surgical curricula. Evaluation of surgical skills is usually done by subjective evaluation, a technique with unknown validity and poor reliability.

Periurethral collagen injection: a long-term follow-up study.

OBJECTIVE: To determine the long-term success of the periurethral injection of collagen (Contigen(R), Bard UK) in women with genuine stress incontinence. PATIENTS AND METHODS: Sixty-one women with genuine stress incontinence were enrolled in a trial of periurethral collagen injections between 1 September 1990 and 31 August 1992. They were assessed at 1, 3, 6, 12 and 24 months after the last collagen injection. In 1998, their notes were reviewed, and a standardized questionnaire was sent to 46 women who were still alive and had undergone no further anti-incontinence surgery. RESULTS: Of the 53 women who were either known failures or who had follow-up information beyond 5 years, 26% were subjectively improved. Women who had a maximum urethral closure pressure of >20 cmH2O and those who had urinary incontinence for <10 years before their first injection were more likely to have had long-term success. There was no correlation between long-term success and the number of previous operations, body mass index, age or preoperative pad loss. Neither the number of injection sessions, total volume of collagen injected nor perceived bulking at the time of surgery affected long-term success rates. Of the 14 women who considered themselves subjectively improved, seven had daily incontinence and only one was completely dry. Urinary retention and urinary tract infection were the most common complications. In addition, one woman reported a flare-up of her skin test and transient 'flu-like symptoms 2 weeks after the injection, and one woman developed a right upper lobe pneumonia 2 weeks after the collagen injection. CONCLUSION: The long-term results of periurethral collagen injections are disappointing. We found no evidence to support the use of periurethral collagen injections in women with intrinsic sphincter deficiency, who had a higher failure rate than those with hypermobility. Further research is essential to develop agents that are not immunogenic, produce minimal inflammatory response and yet are durable.

Coexpression of CCR5 and IL-2 in human genital but not blood T cells: implications for the ontogeny of the CCR5+ Th1 phenotype.

Memory T cells that home to inflamed tissues typically express the beta-chemokine receptor CCR5 and exhibit a Th1 cytokine profile. The migration of these cells into the genital tract following antigenic exposure has particular relevance to acquisition of HIV-1 infection, because CCR5 functions as the coreceptor for most sexually transmitted HIV-1 strains. We recently established methodology to purify and culture mononuclear cells from the female reproductive tract, and here we analyzed the phenotype, CCR5 expression, and cytokine production of cervicovaginal T cells in up to 16 donors. The proportion of mucosal T cells expressing CCR5 was markedly expanded as compared with peripheral blood (mean 88% vs 24% in 13 donors), but the receptor density on individual CCR5+ T cells was only slightly increased (mean 5837 vs 4191 MEPE (molecules of equivalent PE) units in 6 of 7 donors). Intracellular costaining for IL-2, IFN-gamma, IL-4, and IL-5 revealed a Th1-type pattern in cervical T cells, with significantly higher percentages of IL-2- and IFN-gamma-producing T cells in the mucosa than in blood (mean 67% vs 29%). Coexpression of surface CCR5 with intracellular IL-2 and IFN-gamma was observed only among T cells in the mucosa, but not among those in circulation. Thus, we postulate that T cell homing to the genital mucosa leads to differentiation into the combined CCR5+ Th1 phenotype. Moreover, the predominance of CCR5+ Th1-type T cells in normal cervical mucosa provides targets accessible for the efficient transmission of macrophage-tropic HIV-1 variants in women following sexual exposure.

Dendritic cell-T-cell interactions support coreceptor-independent human immunodeficiency virus type 1 transmission in the human genital tract.

Worldwide, human immunodeficiency virus (HIV) is transmitted predominantly by heterosexual contact. Here, we investigate for the first time, by examining mononuclear cells obtained from cervicovaginal tissue, the mechanisms whereby HIV type 1 (HIV-1) directly targets cells from the human genital tract. In contrast to earlier findings in mucosal models such as human skin, we demonstrate that the majority of T cells and macrophages but none or few dendritic cells (DC) express the HIV-1 coreceptor CCR5 in normal human cervicovaginal mucosa, whereas all three cell types express the coreceptor CXCR4. To understand the role of coreceptor expression on infectivity, mucosal mononuclear cells were infected with various HIV-1 isolates, using either CCR5 or CXCR4. Unstimulated T cells become rapidly, albeit nonproductively, infected with R5- and X4-tropic variants. However, DC and T cells form stable conjugates which permit productive infection by viruses of both coreceptor specificities. These results indicate that HIV-1 can exploit T-cell-DC synergism in the human genital tract to overcome potential coreceptor restrictions on DC and postentry blocks of viral replication in unactivated T cells. Thus, mononuclear cells infiltrating the genital mucosa are permissive for transmission of both R5- and X4-tropic HIV-1 variants, and selection of virus variants does not occur by differential expression of HIV-1 coreceptors on genital mononuclear cells.

Menstrual cycle variability in midazolam pharmacokinetics.

Activity of cytochrome P450 3A4 (CYP3A4), the most abundant human P450 isoform and responsible for metabolizing approximately half of all therapeutic agents, has been speculated to vary during the menstrual cycle. This investigation evaluated CYP3A4 activity during the menstrual cycle, using midazolam clearance as a metabolic probe. Midazolam (1 mg i.v.) was administered to nonsmoking, nonpregnant female volunteers (N = 11, age 26 +/- 5 years) with normal menstrual cycles on three separate occasions during the same cycle: days 2 (menstrual phase), 13 (estradiol peak), and 21 (progesterone peak). Venous plasma midazolam concentrations were determined by gas chromatography-mass spectrometry. Midazolam clearance was determined by noncompartmental and compartmental analysis. Midazolam plasma disposition did not differ between phases of the menstrual cycle. There was no significant difference in any measure of midazolam clearance. Noncompartmental clearances (mean +/- SD) were 7.36 +/- 2.73, 6.34 +/- 3.59, and 6.23 +/- 2.04 ml/kg/min, respectively, on days 2, 13, and 21 of the menstrual cycle. These results suggest no difference in hepatic CYP3A4 activity on menstrual cycle days 2, 13, and 21. Consideration of menstrual cycle variability in the metabolism of CYP3A4 substrates does not appear indicated in the dosing or design of clinical trials.

Formal teaching of surgical skills in an obstetric-gynecologic residency.

OBJECTIVE: To describe a formal teaching program of basic surgical skills in an obstetric-gynecologic residency program and evaluate its effectiveness. METHODS: A surgical skills program was developed for all residents. Using bench and animal laboratory sessions, residents were given instruction and performed both laparoscopic and open abdominal procedures. All were given a pretest and were tested again 6 months later. Residents also evaluated their experiences. RESULTS: To date, the formal teaching sessions have been given to 24 residents, all of whom believed their confidence and technical skills improved as a result of the sessions. On a scale of 1 to 5, the median rating of the bench laboratory experience was 5 (range 4-5), and the pig laboratory was 5 (range 4-5). All residents believed the surgery sessions should be continued and the number of sessions increased. Preliminary evaluation indicated that time to suture a 10-inch incision decreased by 28%, from an average of 225 (standard deviation [SD] 51) seconds to 171 (SD 43) seconds (P < .001), and evaluation of surgical technique significantly improved at the second pretest (P = .013). Laparoscopic placement of pegs on a board in 2 minutes increased from an average of 5 (SD 2.5) to 7.3 (SD 2.6; P = .001). The cost of the bench laboratory sessions was minimal. Each pig was approximately $100, and the facility charge for each 4-hour laboratory session was $1500. CONCLUSION: When formal surgical training was given to obstetric-gynecologic residents, their surgical skills improved subjectively and objectively.

Assessment of cytochrome P450 3A4 activity during the menstrual cycle using alfentanil as a noninvasive probe.

BACKGROUND: Gender-dependent differences in cytochrome P450 activity, drug metabolism, drug elimination, and their clinical consequences are increasingly apparent. P450 3A4 is the most abundant P450 isoform in the human liver and is responsible for metabolizing a vast and diverse assortment of therapeutic agents, including opioids, benzodiazepines, and local anesthetics. P450, 3A4 activity is higher in women, influenced by steroid hormone levels, and is speculated to vary during the menstrual cycle. This investigation tested the hypothesis that P450 3A4 activity varies during the menstrual cycle. Alfentanil clearance was used as a metabolic probe for P450 3A4 activity. METHODS: Alfentanil (20 micrograms/kg bolus) was administered to nine nonsmoking, nonpregnant female volunteers (age, 26 +/- 5 yr) with normal menstrual cycles on three separate occasions during the same menstrual cycle: days 2 (menstrual phase), 13 (estrogen peak), and 21 (progesterone peak). Venous plasma alfentanil concentrations were determined by gas chromatography-mass spectrometry. Alfentanil clearance was determined by noncompartmental methods and by a three-compartment model with both pooled population and two-stage analysis. RESULTS: There was no significant difference in any measure of alfentanil clearance. Noncompartmental clearances (mean +/- SD) were 3.62 +/- 0.76, 3.81 +/- 0.96, and 3.60 +/- 0.84 ml/kg/ min, respectively, on days 2, 13, and 21 of the menstrual cycle. CONCLUSIONS: Alfentanil clearances were not different on menstrual cycle days 2, 13, and 21, strongly suggesting no change in P450 3A4 activity. Menstrual cycle differences in alfentanil clearances do not contribute to interindividual variability in alfentanil disposition in women. If other P450 3A4 substrates are comparable, then menstrual cycle variability in their metabolism may not be a consideration in dosing or in the design of pharmacokinetic investigations.

Parent characteristics, perceived health risk, and smokeless tobacco use among white adolescent males.

The results of this study indicate that father education, father use of smokeless tobacco, and adolescent risk perception contribute to the use of smokeless tobacco by white males 12 to 14 years of age. However, risk perception does not account for the correlation between parent characteristics and child behavior. Father education and child smokeless tobacco use are inversely related if the father does not use it, and they are directly related if the father does; this finding is consistent with theories of modeling but is contrary to the common observation that the use of some abusive substances is relatively low among adolescents in higher social and economic levels. We concluded that father characteristics should be considered in research and in programs pertaining to the use of smokeless tobacco by white adolescent males.

Saturnian trapped radiation and its absorption by satellites and rings: the first results from pioneer 11.

Electrons and protons accelerated and trapped in a Saturnian magnetic field have been found by the University of Chicago experiments on Pioneer 11 within 20 Saturn radii (Rs) of the planet. In the innermost regions, strong absorption effects due to satellites and ring material were observed, and from approximately 4 Rs inwards to the outer edge of the A ring at 2.30 Rs (where the radiation is absorbed), the intensity distributions of protons (>/= 0.5 million electron volts) and electrons (2 to 20 million electron volts) were axially symmetric, consistent with a centered dipole aligned with the planetary rotation axis. The maximum fluxes observed for protons (> 35 million electron volts and for electrons < 3.4 million electron volts) were 3 x 10(4) and 3 x 10(6) per square centimeter per second, respectively. Absorption of radiation by Mimas provides a means of estimating the radial diffusion coefficient for charged particle transport. However, the rapid flux increases observed between absorption features raise new questions concerning the physics of charged particle transport and acceleration. An absorption feature near 2.5 Rs has led to the discovery of a previously unknown satellite with a diameter of approximately 200 kilometers, semimajor axis of 2.51 Rs, and eccentricity of 0.013. Radiation absorption features that suggest a nonuniform distribution of matter around Saturn have also been found from 2.34 to 2.36 Rs, near the position of the F ring discovered by the Pioneer imaging experiment. Beneath the A, B, and C rings we continued to observe a low flux of high-energy electrons. We conclude that the inner Saturn magnetosphere, because of its near-axial symmetry and the many discrete radiation absorption regions, offers a unique opportunity to study the acceleration and transport of charged particles in a planetary magnetic field.