Determining health-related quality of life and health state utility values of recurrent urinary tract infections in women.

INTRODUCTION AND HYPOTHESIS: Health state utility values estimate an individual's valuation of their health-related quality of life. Despite prevalence of recurrent urinary tract infections (rUTIs), the health state utility value of rUTIs is unknown. The primary aim was to determine the utility value of rUTIs using the standard gamble (SG). The secondary aim was to compare the SG utility value with that derived from the EuroQol 5 dimensions (EQ-5D) and visual analog scale (VAS). We hypothesized that a utility value would be successfully derived from the SG and would differ from that derived using the EQ-5D and VAS. METHODS: Nonpregnant, adult English-speaking female patients with a diagnosis of rUTI were recruited and completed the EQ-5D, VAS, and SG (n = 25). Utility values were evaluated using Wilcoxon signed-rank tests and Spearman's rho correlation. RESULTS: Health state utility values varied depending on the assessment tool used: EQ-5D 0.76 (IQR 0.52), VAS 0.70 (IQR 0.30), and SG 0.85 (IQR 0.25). There were differences between VAS and the other two assessment methods (p<0.001), as well as between EQ-5D and SG (p=0.013). Spearman correlation demonstrated a moderately positive correlation between EQ-5D and VAS values (r(25) = 0.59, p=0.0019). CONCLUSIONS: Our data suggest that 0.85 reflects the true health state utility value of rUTIs among nonpregnant adult English-speaking women. The utility value for recurrent UTIs is worse (lower) than that previously published for nonrecurrent UTIs, reflecting the ability of the SG to convey the compounding impact of recurrent disease. In this study, neither the EQ-5D nor the VAS produced results consistent with those found using the SG, which suggests limited validity in this population.

Computational simulation methodologies for mechanobiological modelling: a cell-centred approach to neointima development in stents.

The design of medical devices could be very much improved if robust tools were available for computational simulation of tissue response to the presence of the implant. Such tools require algorithms to simulate the response of tissues to mechanical and chemical stimuli. Available methodologies include those based on the principle of mechanical homeostasis, those which use continuum models to simulate biological constituents, and the cell-centred approach, which models cells as autonomous agents. In the latter approach, cell behaviour is governed by rules based on the state of the local environment around the cell; and informed by experiment. Tissue growth and differentiation requires simulating many of these cells together. In this paper, the methodology and applications of cell-centred techniques--with particular application to mechanobiology--are reviewed, and a cell-centred model of tissue formation in the lumen of an artery in response to the deployment of a stent is presented. The method is capable of capturing some of the most important aspects of restenosis, including nonlinear lesion growth with time. The approach taken in this paper provides a framework for simulating restenosis; the next step will be to couple it with more patient-specific geometries and quantitative parameter data.

The role of vessel geometry and material properties on the mechanics of stenting in the coronary and peripheral arteries.

There have been notably higher rates of restenosis with stents used to restore blood flow to many stenosed peripheral arteries compared with their coronary counterparts. The mechanical environment of arteries such as the femoral and popliteal (and the stent fracture that this can cause) has previously been identified as a contributing factor to the relatively low success rates for this procedure. The aim of this study was to investigate how other factors, namely the differences in geometries and mechanical properties of the arteries and the stents used in them, might influence the outcome in these different arteries. Finite element models of the stents and arteries were created, and the results compared in terms of stresses induced in the arteries, the lumen gain, and the deformation of the stent due to pulsatile loading. It was found that deploying a Nitinol stent in a peripheral artery induced lower stresses in the vessel wall than expanding a stainless steel stent in a coronary artery, although the lumen gain was also lower. The predicted strain amplitude induced in Nitinol stents by the cardiac cycle was below the value required to cause fatigue failure. This study does not provide any evidence to suggest that differences in the geometry and material properties between peripheral and coronary arteries, or the types of stent used to restore vessel patency, are the dominate factors responsible for the higher rates of restenosis observed in peripheral arteries.

Ventricular arrhythmia, Cheyne-Stokes respiration, and death: observations from patients with defibrillators.

OBJECTIVE: To determine whether ventricular arrhythmia related to nocturnal hypoxaemia during Cheyne-Stokes respiration (CSR) explains the observation that CSR is an independent marker of death in heart failure. DESIGN: Prospective, observational study. PATIENTS: 101 patients at high risk of clinical serious ventricular arrhythmia fitted with an implantable cardioverter-defibrillator (ICD). MEASUREMENTS: Patients were studied at baseline for CSR during sleep. Arrhythmia requiring device discharge was used as a surrogate marker for possible sudden cardiac death. RESULTS: 101 patients (42 with CSR) were followed up for a total of 620 months. Twenty six patients experienced 432 ICD discharge episodes. Twenty four (6%), 210 (49%), 125 (29%), and 73 (17%) episodes occurred across the time quartiles 0000-0559, 0600-1159, 1200-1759, and 1800-2359, respectively. Kaplan-Meier analysis showed a relative risk of 1 (95% confidence interval 0.5 to 2.2, p = 1) for device discharge in the CSR group. The average (SED) numbers of nocturnal ICD discharges per patient per month of follow up were 0.01 (0.01) and 0.04 (0.02) for patients with and without CSR, respectively (p = 0.6). CONCLUSION: These findings refute the proposition that CSR is related to heart failure death through nocturnal serious ventricular arrhythmia.

Disseminated Pseudallescheria boydii (Scedosporium apiospermum) infection in a renal transplant patient.

Transplant recipients receive a number of immunosuppressive medications that result in an increased risk of infection, including infections with microbes that are normally not pathogenic. We describe a patient with end-stage renal disease who underwent kidney transplantation. Six months postoperatively, he presented with a lesion on his ankle, multiple thigh nodules, and right testicular pain. Biopsy of the ankle lesion demonstrated Pseudallescheria boydii (Scedosporium apiospermum), a common environmental fungus. Following orchiectomy, multiple fungal elements were found that were initially described as Aspergillus species, but later identified as P. boydii. In addition, multiple brain abscesses were found on magnetic resonance imaging. Despite treatment with multiple antifungal medications, the patient died of cardiac dysrhythmia. Current diagnostic and therapeutic alternatives for P. boydii are reviewed.

[123I]beta-CIT SPECT imaging assessment of the rate of Parkinson's disease progression.

BACKGROUND: [123I]beta-CIT and SPECT imaging of the dopamine transporter is a sensitive biomarker of PD onset and severity. OBJECTIVE: In this study, the authors examine the change in [123I]beta-CIT uptake in sequential SPECT scans to assess the rate of progression of the dopaminergic terminal loss in patients with PD. METHODS: Patients with PD (n = 32) and healthy controls (n = 24) recruited from the Yale Movement Disorders Center underwent repeat [123I]beta-CIT SPECT imaging during a 1- to 4-year period. The primary imaging outcome was the ratio of specific to nondisplaceable striatal activity. Disease severity was assessed by Hoehn and Yahr staging, and Unified Parkinson Disease Rating Scale after 12 hours off drug. RESULTS: Sequential SPECT scans in PD subjects demonstrated a decline in [123I]beta-CIT striatal uptake of approximately 11.2%/year from the baseline scan, compared with 0.8%/year in the healthy controls (p < 0.001). Although [123I]beta-CIT striatal uptake in the PD subjects was correlated with clinical severity, the annual percentage loss of [123I]beta-CIT striatal uptake did not correlate with the annual loss in measures of clinical function. CONCLUSIONS: - The rate of dopaminergic loss in PD is significantly greater than that of healthy controls, and [123I]beta-CIT SPECT imaging provides a quantitative biomarker for the progressive nigrostriatal dopaminergic degeneration in PD. As new protective and restorative therapies for PD are developed, dopamine transporter imaging offers the potential to provide an objective endpoint for these therapeutic trials.

Phase I study of Gliadel wafers plus temozolomide in adults with recurrent supratentorial high-grade gliomas.

Both Gliadel wafers [1,3-bis(2-chloroethyl)-1-nitrosourea] and temozolomide (TEMO) have been shown in independent studies to prolong survival of patients with recurrent malignant glioma following surgery and radiotherapy. On the basis of preclinical evidence of synergism between Gliadel wafers and TEMO, a phase I study was designed to evaluate the toxicity of combining these 2 agents in the treatment of patients with recurrent supratentorial malignant glioma. All patients had surgical resection of the tumor at relapse, and up to 8 Gliadel (3.85%) wafers were placed in the surgical cavity following resection. Two weeks after surgery, TEMO was given orally daily for 5 days. Cohorts of 3 patients received TEMO at daily doses of 100 mg/m2, 150 mg/m2, and 200 mg/m2, respectively. Patients were assessed for toxicity 4 weeks after start of the first course of TEMO. Contrast-enhanced MRI of the brain was used to assesstumor response after the first cycle of TEMO. Patients with stable disease or response after the first cycle of TEMO were allowed to continue treatment at the same dose every 4 weeks for 12 cycles or until disease progression or unacceptable toxicity. Ten patients with a median age of 47 years (range, 22-66 years) were enrolled in this study. There were 7 patients with glioblastoma multiforme and 3 patients with anaplastic astrocytoma. Three patients were treated with TEMO at the first dose level of 100 mg/m2, 4 at the second dose level of 150 mg/m2, and 3 at the third dose level of 200 mg/m2. The 10 patients received a median of 3 cycles (range, 1-12 cycles) of TEMO following placement of Gliadel wafers. The treatment was well tolerated, with only 1 patient suffering grade III thrombocytopenia at the highest dose level. Two patients at each dose level had no evidence of disease progression after treatment. Four patients suffered progressive disease on therapy. Our study demonstrates that TEMO can be given safely after placement of Gliadel (3.85%) wafers. The recommended dosage for TEMO for a phase II study of this combination is 200 mg/m2 per day for 5 days.

Application of a mixed-mode solid-phase extraction and cleanup procedure for LC/MS determination of thiabendazole and carbendazim in apple juice.

Recently, a mixed-mode solid-phase extraction (SPE) procedure was developed for rapid extraction and cleanup for determination of the fungicides thiabendazole and carbendazim in various fruit juices. This paper reports the application of that sample preparation procedure to the liquid chromatographic/mass spectrometric determination of these fungicides in apple juice with detection by positive electrospray ionization mass spectrometry (ESI/MS). Response was linear for sample concentrations from 2 to 500 microg/L (ppb). Recoveries averaged 74% (9% RSD) for carbendazim and 93% (9% RSD) for thiabendazole. After SPE cleanup, no matrix supression was observed for the ESI+ response for either compound studied. The method was applied to the analysis of incurred residues in 4 store-bought apple juices; carbendazim levels ranged from 10 to 70 microg/L and thiabendazole levels ranged from less than 2 to 130 microg/L.

Effectiveness of an intervention to increase construction workers' use of hearing protection.

In this project we tested the effectiveness of a theory-based intervention (video, pamphlets, and guided practice session) to increase the use of hearing protection devices (HPDs) among Midwestern construction workers and a national group of plumber/pipefitter trainers. Posttest measures were collected 10-12 months following this intervention. Pender's Health Promotion Model (1987) provided the conceptual basis for development of the training program. A total of 837 high-noise-exposed workers were included in the analysis: 652 regional Midwestern construction workers and 185 national plumber/pipefitter trainers. Effectiveness of the intervention was determined through the sequence of analyses recommended by Braver and Braver (1988) for the Solomon Four-Group Design. Analysis of variance and covariance of postintervention use and intention to use HPDs and a meta-analytic test were done. These analyses indicated that the intervention significantly increased use of HPDs but had no effect on intention to use HPDs in the future. Pretesting had no effect on use. Actual or potential applications of this research include guidance in the development of successful theory-based interventions to increase use of HPDs.

A risk assessment of multiple use of an aerosol system compared with single use for lung ventilation scans.

Over 300 99Tc(m)-DTPA aerosol lung ventilation scans are performed at Leicester Royal Infirmary each year. Current practice is to re-use the nebulizer circuits up to five times over a maximum of 1 week. Following a visit from the hospital infection control team, this practice was questioned and, therefore, a risk assessment was carried out. This compared the risks of multiple use of ventilation circuits with single use. A survey was also carried out to try and establish current practice in other departments. The risk assesment showed that both single and multiple use of nebulizer circuits can have a high risk. The risks associated with the former were radiation safety and/or financial, and the risk with the latter was cross-infection. The survey showed that multiple use is certainly common practice within the UK. Therefore, in coming to a decision on which practice to adopt, these risks must be considered most carefully in the context of the local environment.

Sense of belonging and indicators of social and psychological functioning.

Sense of belonging has recently been described and defined as one specific interpersonal process that influences health. The purpose of this study was to examine the relationships between sense of belonging and personal characteristics and selected indicators of social and psychological functioning in men and women. Using a sample of 379 community college students, sense of belonging was examined in relation to social support, conflict, involvement in community activities, attendance at religious services, loneliness, depression, anxiety, history of psychiatric treatment, and suicidality. Results indicated that sense of belonging is closely related to indicators of both social and psychological functioning. These relationships were generally stronger for women than for men. It appears that sense of belonging is a useful concept pertinent to exploration of social and psychological functioning.

Platelet deposition after angioplasty is abolished by restoration of the endothelial cell monolayer.

PURPOSE: Percutaneous transluminal angioplasty of an atheromatous plaque causes endothelial desquamation and intimal dissection with the consequent formation of a thrombogenic flow surface. In this study we investigated the hypothesis that platelet deposition after balloon angioplasty may be decreased by rapid restoration of the endothelial cell monolayer, achieved by transluminally seeding angioplasty sites with endothelial cells. METHODS: Bilateral external iliac angioplasty was performed in eight New Zealand white rabbits. One angioplasty site was isolated from the circulation and incubated with a supraconfluent endothelial cell suspension with a double balloon catheter; the contralateral angioplasty site was sham seeded with culture medium. The deposition of autologous indium 111-labeled platelets on the angioplasty sites was quantified 30 minutes after restoration of flow and was referenced to an undamaged segment of aorta that acted as a negative control. RESULTS: Platelet deposition on the nonseeded angioplasty site (13.1 x 10(4) platelets/mm2) was significantly higher than on nondilated segments (3.4 x 10(4) platelets/mm2; p = 0.014). Restorationof endothelial cell coverage by endothelial seeding significantly reduced platelet deposition on dilated arterial segments to levels not significantly higher than in controls (3.6 x 10(4) platelets/mm2; p = 0.014). CONCLUSIONS: These results illustrate that rapid reendothelialization of angioplasty sites decreases subsequent platelet deposition and may reduce the rate of acute arterial reocclusion complicating endovascular techniques.

Expression of hormone receptors, cathepsin D, and HER-2/neu oncoprotein in normal colon and colonic disease.

BACKGROUND: Chronic ulcerative colitis and familial adenomatous polyposis are associated with an increased risk of colorectal carcinoma. Currently, there are no reliable methods to assess carcinoma risk. METHODS: Several prognostic factors known to be useful in breast carcinoma were determined in 102 specimens of colonic mucosa from 38 patients: 22 specimens from "normal," non-neoplastic colon, 49 from chronic ulcerative colitis, 10 from Crohn's colitis, 14 from familial adenomatous polyposis, four from mucosa adjacent to carcinoma, and three from colon carcinoma. Expression of estrogen receptor, progestin receptor, epidermal growth factor receptor, HER-2/neu (c-erb B-2) oncoprotein, and cathepsin D were determined. RESULTS: Epidermal growth factor receptor expression was higher in chronic ulcerative colitis, Crohn's colitis, familial adenomatous polyposis, and colon carcinoma and varied with location within the colon for chronic ulcerative colitis, Crohn's colitis, and familial adenomatous polyposis. Epidermal growth factor receptor expression in mucosa adjacent to carcinoma was similar to that in "normal" colon. CONCLUSION: Further analyses are needed to determine which parameters are related to and possibly predictive of increased carcinoma risk.

Evaluation of changes in myocardial function on exercise in patients with coronary artery disease using gated MIBI scintigraphy.

Technetium-99m-methoxy-isobutyl-isonitrile (MIBI) is a myocardial perfusion agent which allows simultaneous assessment of left ventricular function. We evaluated left ventricular (LV) function with exercise using a new method of myocardial profiling in 43 patients with chest pain. Twenty-eight had significant coronary artery disease and 15 were normal on coronary angiography. Results were compared to equilibrium radionuclide ventriculography. MIBI fractional shortening (FS) correlated well with ejection fraction (EF) on exercise (r = 0.79, P = less than 0.001). There was also a good correlation between changes in global function from rest to exercise (r = 0.82, P = less than 0.001) with a sensitivity of diagnosing CAD of 71% and specificity of 80%. New regional wall abnormalities were detected in 25/28 with CAD with a sensitivity of 89% and specificity of 60%. There was also a close correlation between mean diameters measured with gated MIBI scans and volumes measured with RNV, end-diastolic diameter (EDD) versus end-diastolic volume (EDV) r = 0.78 (P = less than 0.001) at rest and r = 0.74 (P = less than 0.001) on exercise and end-systolic diameter (ESD) versus end-systolic volume (ESV) r = 0.72 (P = less than 0.001) at rest and r = 0.72 (P = less than 0.001) on exercise. This produced a sensitivity for detecting CAD of 79% and a specificity of 73%. These results show that gated MIBI scanning on exercise provides information comparable to RNV so enhancing the diagnostic usefulness of MIBI.

A BASIC algorithm for calculating the postmortem interval from arthropod successional data.

A computer algorithm, implemented in the BASIC language, is presented for calculating the postmortem interval (PMI) from arthropod successional data. Entomology-assisted determination of the PMI promises to be a reliable technique in cases of homicide, suicide, accidental death, and unattended death due to natural causes. The program requires, as input, the identity of arthropod taxa recovered from human remains in a death scene investigation and machine-readable data on carrion-associated arthropod taxa and their known successional patterns of activity for the same geographical area. The program performs rapid comparisons of these lists and, on output, calculates an upper and lower estimate of the PMI, identifies the definitive taxa for these limits, and determines if the remaining corpse taxa have known successional patterns that are consistent for this estimate. An alternate output is provided if one or more corpse taxa do not overlap all the others at any single time in the succession. In that event, the user is prompted to recheck the identity of the non-overlapping taxon or taxa or reevaluate the environmental circumstances surrounding the case in question. Results of the analysis are saved to an ASCII file for output to a printer for making paper copies useful for the entomologist's Case Study Final Report. This program may make possible wider use of this technique in law enforcement and medical investigator offices that utilize both forensic entomologist expertise and IBM PCs (or compatible computers).

Gated 99Tcm-MIBI myocardial function imaging.

The introduction of the 99Tcm isonitrile perfusion agents has provided improved myocardial image quality with conventional imaging equipment allowing improved edge definition on gating. We evaluated left ventricular wall motion in 46 patients using gated 99Tcm-2-methoxy-2-methyl-isopropyl-1-isonitrile (MIBI) scintigraphy. Using a method of myocardial profiles in four axes, global and regional fractional shortening (FS) were assessed. A good correlation was found between FS in the left anterior oblique (LAO) 40 degrees projection and ejection fraction (EF) on gated radionuclide ventriculography (r = 0.81, P less than 0.001). This was improved by using FS in two planes, LAO 40 degrees and anterior (r = 0.88, P less than 0.001). There was also a good correlation between FS in two planes and EF on cine-angiography (r = 0.72, P less than 0.001). There was good intra- and interobserver agreement with the studies. Assessment of myocardial function using gated MIBI imaging and myocardial profiles provides useful additional information to the perfusion scan, thus enhancing the diagnostic usefulness of the agent.