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Biomedical subjects

R Moore

Publications and source records attributed to R Moore.

At least 19 recordsLinked to original sources
PubMed2006

The prognostic significance of lower uterine segment involvement in surgically staged endometrial cancer patients with negative nodes.

OBJECTIVES: Endometrial cancer is the most common female genital malignancy in the United States. Stage is the most important prognostic factor. Other factors include grade, lymph-vascular space invasion (LVI), and myometrial invasion. Tumor location in the lower uterine segment (LUS) may also be important. LUS involvement correlates with nodal involvement, and nodal involvement is an important prognostic indicator. This study investigates the importance of LUS involvement in patients with pathologically negative nodes. METHODS: This was an IRB approved retrospective study. Data were collected for patients diagnosed with endometrial cancer from June 1999 to September 2004. Patients who underwent nodal evaluation with no evidence of nodal disease were eligible for analysis. The primary endpoint was progression-free survival. Secondary endpoints included recurrence rate and overall survival. Analysis was performed with the JMP5.1 statistical program. RESULTS: 285 patients were identified. 85 were excluded because they received postoperative care elsewhere. 3 charts were missing, and 15 pathology reports did not mention LUS. 147 of the remaining 182 subjects had negative nodes and formed the study population. 57% of these subjects had LUS involvement. Follow-up was similar for those with and without LUS involvement at 74 vs. 73 months respectively. PFS was similar at 70 and 63 months in those with and without LUS involvement (p=0.2). Recurrence correlated with LUS involvement on univariate analysis, however, not on multivariate analysis. CONCLUSIONS: In endometrial cancer patients with negative nodes, disease within the lower uterine segment does not imply a worse prognosis. The previously described implications of LUS involvement are likely due to the strong association of LUS disease with lymph node spread.

Aged↗
PubMed2006

Efficacy and safety of topiramate in combination with metformin in the treatment of obese subjects with type 2 diabetes: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To investigate the efficacy and safety of topiramate in obese subjects with type 2 diabetes treated with metformin. DESIGN: This was a multicenter, double-blind, placebo-controlled trial. All subjects received a non-pharmacological program of diet, exercise and behavioral modification throughout the study; the assigned diet was 600 kcal/day less than the subject's individually calculated energy expenditure. After a 6-week single-blind placebo run-in, subjects were randomized to placebo, topiramate 96 mg/day or topiramate 192 mg/day. Following an 8-week titration period, subjects remained on their assigned dose for 52 weeks. However, the sponsor ended the study early in order to develop a new controlled-release formulation with the potential to enhance tolerability and simplify dosing in this patient population. A total of 646 obese men and women (age: 18-75 years, body mass index: 27-50 kg/m(2)) with an established history of type 2 diabetes mellitus controlled by metformin monotherapy were randomized. Efficacy was assessed in a pre-determined modified intent-to-treat (MITT) population of 307 subjects whose randomization date would have allowed them to complete 24 weeks on study medication before the announcement of study termination. MEASUREMENTS: Joint primary efficacy parameters were mean percent change in weight and change in glycosylated hemoglobin (HbA(1c)) from baseline to week 24. RESULTS: Subjects in the placebo, topiramate 96 mg/day and topiramate 192 mg/day groups lost 1.7%, 4.5% (P<0.001) and 6.5% (P<0.001), respectively, of their baseline body weight and had absolute decreases in HbA(1c) of 0.1%, 0.4% (P<0.001) and 0.6% (P<0.001) (MITT, last observation carried forward). Topiramate-treated subjects also experienced statistically significant decreases in systolic blood pressure. Most common adverse events were paresthesia and events related to the central nervous system. CONCLUSIONS: Topiramate was effective for weight reduction and improvement in glycemic control in obese subjects with type 2 diabetes treated with metformin monotherapy. Further study in obese diabetics is warranted.

Adolescent↗
PubMed2006

Antiretroviral use and other risks for HIV-associated neuropathies in an international cohort.

OBJECTIVE: To explore the association between specific nucleoside reverse transcriptase inhibitors and sensory neuropathies (SNs) and define the modifying roles of hepatitis C (HCV), vitamin B12 deficiency, and impaired glucose tolerance. METHODS: The authors conducted a prospective cohort study of 147 HIV-infected adults at two sites chosen to emphasize demographic differences. Standardized assessments included detailed antiretroviral histories, neurologic examinations, skin biopsies for epidermal nerve quantitation, and quantitative sensory testing. RESULTS: There were significant differences between subjects at Johns Hopkins University (JHU) and Monash University (MU) in gender, race, HIV transmission route, and HCV seroprevalence. Symptomatic SN was present in 49% at JHU and 55% at MU (chi2 = 4.02, p = 0.134) and was significantly more common in those at least age 40 than younger patients (odds ratio [OR] = 2.87, 95% CI = 1.27, 6.49). After adjusting for site, age, and CD4 cell count, exposure to didanosine (ddI) or stavudine (d4T) was associated with an significantly increased likelihood of symptomatic SN (ddI: OR = 3.21, 95% CI: 1.56, 6.60; d4T: OR = 7.66, 95% CI: 2.89, 20.33). Plasma HIV RNA, lactate, and HCV were not associated with SN. Quantitative vibratory testing identified neuropathy with a positive predictive value of 76% and epidermal nerve fiber densities 59%. CONCLUSIONS: Exposure to stavudine and didanosine was significantly associated with a heightened risk for symptomatic sensory neuropathy. Reduced vibration thresholds and epidermal nerve fiber densities had the highest diagnostic efficiency of the laboratory indicators of neuropathy examined, but were relatively insensitive in isolation.

Adult↗
PubMed2006

Endografting of the descending thoracic aorta increases ascending aortic input impedance and attenuates pressure transmission in dogs.

OBJECTIVES: Endografting is being used to manage aneurysms, dissections and acute traumatic disruptions of the thoracic aorta. The acute effects of such interventions on ventricular afterload and on pressure wave transmission characteristics are not well known. METHODS: In five dogs, a 55 mm endograft was introduced into the descending aorta, just distal to the left subclavian artery, with oversizing of 20%. Following formaldehyde induced complete heart block, the hearts were paced (30-120bpm). The ascending aortic pressures and flows were recorded using Millar micro-tip manometers and ultrasonic flowmeters, respectively. Arterial pressures proximal and distal to the stent site were also recorded. For each heart rate, parameters of a modified Windkessel (SVR: systemic vascular resistance, Z0: characteristic impedance, C: total arterial compliance) were estimated. The pulse wave velocity (PWV) and reflection coefficient (Gamma) were calculated from the pressure wave transfer functions. RESULTS: The Z0 (0.25+/-0.05 vs 0.41+/-0.06 mmHg/ml s(-1), P<.05) was increased and C was decreased (0.45+/-0.07 vs 0.28+/-0.04 ml/mmHg, P<0.001) following endograft placement. SVR tended to increase (P=.06) and ascending aortic Gamma was unchanged. The PWV increased (418+/-67 vs 755+/-135 cm/s, P<.05) and the distal Gamma decreased (0.09+/-0.10 vs -0.49+/-0.07, P<.05). CONCLUSIONS: Endografting in the proximal descending aorta cause unfavorable changes in the ascending aortic input impedance and an increase in the PWV through the grafted segment, consistent with an increase in the modulus of elasticity. The grafts produce a negative Gamma at the distal end, an uncommon occurrence in the systemic circulation. Whether this change is of sufficient magnitude to result in post-graft dilation is unknown.

Animals↗
PubMed2006

Therapeutic use of cephazolin to prevent complications of spine surgery.

Discitis, caused by pyogenic organisms, is a potential complication of any procedure which involves entering the intervertebral disc during open or percutaneous procedures. While there are wide variations in the severity of symptoms, the characteristic feature of discitis is the development of increasingly severe back pain, which is not relieved by rest, or narcotic analgesics. While there is a tendency to spontaneous resolution over time, a self-limiting course does not always eventuate. Serious complications resulting from spread of the infective process can lead to vertebral osteomyelitis or to the formation of an epidural abscess with further risk of neural compression. Clinical and experimental evidence now supports the prophylactic use of a suitable antibiotic, but some uncertainties exist about the benefits of antibiotic therapy in treating established discitis. While cephazolin is a widely favoured choice of antibiotic, the timing of its administration to prevent or treat discitis has been complicated by the lack of suitable methods for detecting and measuring the concentration of cephazolin in the plasma and disc in experimental and clinical conditions. This paper describes a high-performance liquid chromatography technique for detecting the antibiotic cephazolin. The results conclude cephazolin can be detected in the plasma and disc after administering an intravenous bolus dose. However, concentration of cephazolin in the outer disc was 12 times greater than that of the inner disc.

Animals↗
PubMed2006

Computerized mass detection for digital breast tomosynthesis directly from the projection images.

Digital breast tomosynthesis (DBT) has recently emerged as a new and promising three-dimensional modality in breast imaging. In DBT, the breast volume is reconstructed from 11 projection images, taken at source angles equally spaced over an arc of 50 degrees. Reconstruction algorithms for this modality are not fully optimized yet. Because computerized lesion detection in the reconstructed breast volume will be affected by the reconstruction technique, we are developing a novel mass detection algorithm that operates instead on the set of raw projection images. Mass detection is done in three stages. First, lesion candidates are obtained for each projection image separately, using a mass detection algorithm that was initially developed for screen-film mammography. Second, the locations of a lesion candidate are backprojected into the breast volume. In this feature volume, voxel intensities are a combined measure of detection frequency (e.g., the number of projections in which a given lesion candidate was detected), and a measure of the angular range over which a given lesion was detected. Third, features are extracted after reprojecting the three-dimensional (3-D) locations of lesion candidates into projection images. Features are combined using linear discriminant analysis. The database used to test the algorithm consisted of 21 mass cases (13 malignant, 8 benign) and 15 cases without mass lesions. Based on this database, the algorithm yielded a sensitivity of 90% at 1.5 false positives per breast volume. Algorithm performance is positively biased because this dataset was used for development, training, and testing, and because the number of algorithm parameters was approximately the same as the number.of patient cases. Our results indicate that computerized mass detection in the sequence of projection images for DBT may be effective despite the higher noise level in those images.

Algorithms↗
PubMed2005

Serine 202 regulates the nuclear translocation of constitutive active/androstane receptor.

The constitutive active receptor (CAR) in mouse primary hepatocytes undergoes okadaic acid (OA)-sensitive nuclear translocation after activation by xenobiotics such as phenobarbital (PB) and 1,4 bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP). We have now mimicked this TCPOBOP-dependent and OA-sensitive translocation of mouse CAR (mCAR) in HepG2 cells and have demonstrated that protein phosphatase 2A regulates this nuclear translocation. Site-directed mutagenesis analysis of various Ser and Thr residues delineated the translocation activity to Ser-202. Mutation of Ser-202 to Asp (S202D) prevented mCAR translocation into the nucleus of TCPOBOP-treated HepG2 cells. In addition, in the livers of Car-/- mice, the YFP-tagged S202D mutant did not translocate into the nucleus after PB treatment. To examine whether Ser-202 can be phosphorylated, flag-tagged wild-type mCAR or flag-tagged S202A mutant was expressed in HepG2 cells and subjected to Western blot analysis using an antibody specific to a peptide containing phospho-Ser-202. A high molecular weight phosphorylated form of CAR was detected only with the wild-type mCAR. These results are consistent with the conclusion that the dephosphorylation of Ser-202 is a required step that regulates the xenobiotic-dependent nuclear translocation of mCAR.

Amino Acid Sequence↗
PubMed2005

Alternative delivery of insulin via eye drops.

BACKGROUND: Various insulin delivery systems have been considered for systemic absorption other than injections. Although the ocular route has been suggested, its use is limited by the amount of insulin absorbed systemically via eyes. In order to improve the absorption rate of insulin into systemic circulations, the effects of pH and absorption enhancers were studied with rabbit eyes. METHODS: Insulin eye drops were instilled into eyes of rabbits, and their blood glucose levels were measured with a Glucoscan 200 Meter (Lifescan, Mountain View, CA). RESULTS: Systemic absorption of insulin via the ocular route was much more prominent at higher pH (8.0) than at lower pH (3.5). When absorption enhancers such as glycocholate and fusidic acid were added, the insulin absorption increased further markedly. CONCLUSION: It is feasible to administer insulin through the eyes at pH 8.0 with low concentrations of glycocholate or fusidic acid to achieve the therapeutic efficacy of insulin to lower blood glucose to normal levels.

Absorption↗
PubMed2005

Enhancement of radiation sensitivity with BH3I-1 in non-small cell lung cancer.

BACKGROUND: Anti-apoptotic proteins, such as Bcl-2 and Bcl-xL, are frequently over-expressed in human malignancies, and this is correlated with resistance to chemotherapeutic drugs and gamma- radiation. Recently identified small organic molecules capable of inhibiting Bcl-2 and/or Bcl-xL function, may enhance radiation sensitivity of cancer cells in which they are over expressed. We examined whether specific blockade of the BH3-domain binding to Bcl-xL could sensitize cancer cells to gamma- radiation. METHODS: Human non-small-cell lung cancer H460 cells with wild-type p53 and H1792 cells with mutant p53 were exposed to various doses of radiation and/or BH3I-1 and for different points of time to BH3I-1 treatment. XTT and clonogenic survival assays were used to evaluate the growth-inhibitory effects of the antagonist BH3I-1, ionizing radiation or both. Western blot analysis was used to examine the cellular effect of the expression of Bcl-xL, Bax, and p53. Apoptosis and cell cycle distribution were analyzed by confocal microscopy with Hoechst 33258 staining and cytochrome c, and flow cytometry, respectively. RESULTS: BH3I-1 appeared to induce a dose- and time-dependent apoptosis in H460 and H1792 cells, regardless of p53 status. After 2 days of BH3I-1 treatment, the cells that remained attached were exposed to ionizing radiation. Followed by clonogenic assay, BH3I-1 treatment enhanced the radiation sensitivity of H1792 surviving cells with mutant p53, but not in H460 cells with wild-type p53. A transient time-dependent cell cycle blockade at G2-M phase was identified for H1792 cells without subsequent modification of cell cycle distribution. CONCLUSION: These findings suggest a potential role for the small molecule inhibitor as a novel radiation sensitizer in non-small cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

The tensile properties of tension-free vaginal tape and cadaveric fascia lata in an in vivo rat model.

OBJECTIVE: To examine the tensile properties (break load and maximum average load), after in vivo implantation in a rat animal model, of tension-free vaginal tape (TVT) and cadaveric fascia lata (CFL), as pubovaginal slings of these materials have become popular for treating stress urinary incontinence. MATERIALS AND METHODS: Twenty Sprague-Dawley rats (300-400 g) had 1 x 2 cm strips of commercially available TVT and CFL implanted on the right and left anterior abdominal wall, respectively. Half of the animals were then killed at 6 weeks and the remainder at 12 weeks, after which the strips of TVT and CFL were removed and their tensile properties measured using a tensiometer. The tensile strength of TVT and CFL strips maintained only in normal saline served as controls. RESULTS: The TVT strips had a mean break load of 0.740 kg in the control and only 0.390 kg for CFL (P < 0.05). At 6 weeks the TVT material had a mean (sd) maximum average load of 0.634 (0.096) kg and a mean break load of 0.589 (0.249) kg, whereas the respective values for the CFL were 0.323 (0.198) and 0.167 (0.063) kg (P < 0.05). Similarly at 12 weeks, TVT had a greater mean maximum average and break load than CFL, at 0.742 (0.052) and 0.274 (0.126), and 0.737 (0.056) and 0.185 (0.128) kg, respectively. CONCLUSION: This is the first study to assess the tensile properties of the currently used sling materials, TVT and CFL, in an in vivo model. TVT has a greater break load and maximum average load than CFL; the tensile strength of these materials does not decrease with time.

Animals↗
PubMed2003

Diabetes mellitus in transplantation: 2002 consensus guidelines.

Diabetes mellitus is a serious complication following organ transplantation that is underdiagnosed, possibly due to the inadequate definitions used in published literature and the lack of standardized screening. Diabetes in transplantation amplifies the already increased risk of cardiovascular disease among transplant patients, and increases the risk of graft loss and death. Patients at risk of developing diabetes in transplantation should therefore be prospectively identified and given individualized immunosuppressive therapy to minimize the risk of developing this disease. These guidelines are intended to: (1) help identify patients at risk for diabetes after transplantation; (2) set down a standard definition of posttransplant diabetes mellitus (PTDM); (3) create a standard monitoring protocol for the diagnosis of PTDM; and (4) optimize the management of patients at risk of developing or who develop diabetes after transplantation. With improved diagnosis, individualization of therapy, and proper early management, the incidence of diabetes in transplantation, and the accompanying additional burden of illness the disease carries, may be diminished. In turn, this will help achieve the therapeutic goals of reducing the risk of graft complications, improving quality of life, and reducing postoperative morbidity and mortality in transplant patients.

Consensus↗
PubMed2002

Laser spectroscopy of cooled zirconium fission fragments.

The first on-line laser spectroscopy of cooled fission fragments is reported. The r ions, produced in uranium fission, were extracted and separated using an ion guide isotope separator. The ions were cooled and bunched for collinear laser spectroscopy by a gas-filled linear Paul trap. New results for nuclear mean-square charge radii, dipole, and quadrupole moments are reported across the N=60 shape change. The mean-square charge radii are found to be almost identical to those of the Sr isotones and previously offered modeling of the radial changes is critically reviewed.

Journal Article↗
PubMed2002

On-line ion cooling and bunching for collinear laser spectroscopy.

A new method has been developed for increasing the sensitivity of collinear laser spectroscopy. The method utilizes an ion-trapping technique in which a continuous low-energy ion beam is cooled and accumulated in a linear Paul trap and subsequently released as a short (10-20 micros) bunch. In collinear laser measurements the signal-to-noise ratio has been improved by a factor of 2 x 10(4), allowing spectroscopic measurements to be made with ion-beam fluxes of approximately 50 ions s(-1). The bunching method has been demonstrated in an on-line isotope shift and hyperfine structure measurement on radioactive (175)Hf.

Journal Article↗
PubMed2002

Levatorplasty release and reconstruction of rectovaginal septum using allogenic dermal graft.

The goal of reconstructive vaginal surgery include: restoration of normal anatomy, as well as maintaining visceral and sexual function. Rectocele repair can be performed utilizing a number of techniques, however some of these techniques severely distort the posterior vaginal wall anatomy and subsequently may result in dyspareunia. We report two patients with postoperative dyspareunia following levatorplasty technique for the treatment of rectocele. The patients elected to have their levatorplasty released and their rectovaginal septum reconstructed utilizing allogenic dermal graft. Postoperatively both patients are sexually active without evidence of dyspareunia or rectocele.

Dermis↗
PubMed2002

Tension-free vaginal tape: outcomes among women with primary versus recurrent stress urinary incontinence.

OBJECTIVE: To evaluate the outcomes of tension-free vaginal tape in the treatment of primary versus recurrent genuine stress urinary incontinence. METHODS: A retrospective, multicenter study of 245 consecutive women who were treated with tension-free vaginal tape for genuine stress urinary incontinence (157 for primary and 88 for recurrent genuine stress urinary incontinence) over a 27-month period was performed. Concurrent surgical repairs were performed as required. Subjective and objective outcome data were assessed from routine postoperative visits. Office and hospital records were reviewed to determine patient characteristics, intraoperative findings, and surgical outcomes. RESULTS: Women with recurrent genuine stress urinary incontinence were older (mean age 64.6 versus 59.4 years, P =.004) than those with primary incontinence; they were less likely to have an intact uterus (22.7% versus 66.9%, P <.001), and were more likely to have intrinsic sphincter deficiency (70.5% versus 47.1%, P <.001). The mean duration of follow-up was 38 (+/-16) weeks. Cure rates among patients with recurrent versus primary genuine stress urinary incontinence were similar (85% and 87%, respectively, P =.23). Complication rates were similarly low in both groups (4.5% versus 7.6% for recurrent and primary genuine stress urinary incontinence, respectively, P =.35). Postoperative voiding dysfunction occurred at low rates in both groups. CONCLUSION: Tension-free vaginal tape is a highly effective treatment among patients with recurrent stress incontinence, with outcomes comparable with those among patients with primary incontinence.

Adult↗