Ureterocystoplasty as part of primary closure of bladder exstrophy.
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Biomedical subjects
Publications and source records attributed to P Anderson.
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In behavioural experiments we investigated the influence of previous short exposure to sex pheromone on subsequent response of male Spodoptera littoralis moths to sex pheromone. We found that pre-exposed males showed increased sensitivity to female sex pheromone after a single exposure to a pheromone plume compared to that found in naïve males. The increased responsiveness lasted for at least 27 h after the exposure, showing that it was not just a short-term sensitization of the males. Exposure to the odour source without upwind movement towards the source was enough to increase the responsiveness. Physical activation without exposure to odour did not affect responsiveness. The increase in responsiveness after exposure was higher when the males were pre-exposed to natural female pheromone gland extract than when they were exposed to a higher dose of the main component, even though both odour sources elicited similar upwind attraction in naïve males. Thus, the quality of the pheromone mixture to which males were exposed influenced the subsequent response.
OBJECTIVE: To compare the efficacy and labour costs of nurse continence advisors and urogynaecologists in conservative management of urinary incontinence. DESIGN: Single centre randomised controlled trial of patients with mild or moderate leakage. SETTING: Tertiary urogynaecology unit. SAMPLE: One hundred and forty-five consecutive patients with stress and/or urge incontinence. METHODS: Standardised conservative therapy regimens, provided by nurse continence advisors and urogynaecologists. MAIN OUTCOME MEASURE: One-hour pad test, frequency volume charts, a 20-point incontinence score and two quality of life tests, staff treatment times and costs. RESULTS: Of 110 women who completed 12-week treatments, 64% of the women in the nurse continence advisor group (n = 58) and 52% of women treated by urogynaecologists (n = 52) were asymptomatic (dry pad test; OR 1.63, 95% CI 0.71-3.75). There was no significant difference between clinician groups for change in pad test result (P = 0.71), voids/day (0.43), incontinence score (P = 0.57) or quality of life scores (urogenital distress inventory, P = 0.27; Incontinence Impact Questionnaire, P = 0.41). Despite the expected longer consultation times for the advisor group (median 160 min, interquartile range [IQR] 130-210) versus the urogynaecologist group (median 90 min, IQR 60-120), the per capita labour cost for advisor treatment (median AU$59.20, IQR 48.10-77.70) was lower than for treatment given by urogynaecologists (median cost AU$ 189.70, IQR 120.60-250.70, Mann-Whitney U test, P < 0.0001). At 2.5 years, 23/58 patients (40%) treated by advisor and 27/52 patients (52%) treated by urogynaecologist group, who had been cured and discharged, were available for contact. Of these, 29% of women in the nurse continence advisor group and 41% of those treated by urogynaecologists remained continent (on 20-point score). Quality of life improvement persisted equally in both groups. These data should be interpreted cautiously due to a 24% dropout rate. CONCLUSIONS: The reduction in urine leakage and improvement in quality of life observed in patients treated by nurse continence advisors and urogynaecologists were similar at 12 weeks and 2 years, but lower costs arose from treatment provided by nurse advisors. We suggest that conservative treatment by the nurse continence advisor could be used more widely in mild to moderate incontinence.
Calculations and experiments were used to examine the B(1) field behavior and signal intensity distribution in a 16-cm diameter spherical phantom excited by a 10-cm diameter surface coil at 300 MHz. In this simple system at this high frequency very complex RF field behavior exists, resulting in different excitation and reception distributions. Included in this work is a straightforward demonstration that coil receptivity is proportional to the magnitude of the circularly polarized component of the B(1) field that rotates in the direction opposite to that of nuclear precession. It is clearly apparent that even in very simple systems in head-sized samples at this frequency it is important to consider the separate excitation and reception distributions in order to understand the signal intensity distribution.
Age-related macular degeneration (AMD) is a major public health issue, but little is known about the economics of the disease. This contribution describes the epidemiology and the economics of AMD in four European countries: France, Germany, Italy and the United Kingdom (UK). We reviewed published information on AMD, including guidelines, official statistics, and local literature and interviewed AMD experts. All available health-related quality of life studies (HRQoL) on AMD were also reviewed. Data collection focused on epidemiology, medical management and resource use (both medical and non-medical items). Prevalence of AMD among persons older than 65 years is 8% and increases with age. There are two forms of the disease: atrophic (80-85% of AMD cases) and exudative, which is characterised by choroidal neovascularisation (CNV; 15-20% of AMD cases). No treatment for the atrophic form is available. Laser photocoagulation is the mainstay of treatment for CNV, although less than 30% of persons with CNV can benefit from it. Photodynamic therapy (PDT), a new treatment for CNV, reduces the risk of vision loss in forms with predominantly visible lesions. Several other new procedures are also under development. Rehabilitation and low-vision aids are useful palliative interventions when there is a residual visual acuity. The yearly budget impact of AMD was found to be between 51.3 and 101.1 million euros in the four countries studied. Information on social services and resource use was scant and little is reported on the impact of AMD on HRQoL. Economic studies of AMD should be conducted in order to assist public health decision making.
Sodium hypochlorite (NaOCl) solution,<or=5% w/v available chlorine (abbreviated subsequently to %), is widely used as an irrigant in root canal treatment of teeth, so its effects on dentine are of clinical importance. The effects of approximately 0.5%, 3% and 5% NaOCl solution on the composition of root dentine were studied at ambient temperature. For dentine powder treated for 30 min, depletion of the organic phase was confirmed by infrared spectroscopy. Apatite lattice parameters showed no significant change, but NaCl was also detected by X-ray powder diffraction. The low solubility of apatite mineral in the NaOCl solutions was demonstrated by the constant weight of bulk enamel specimens immersed for seven days. The stability of the mineral phase was confirmed by scanning microradiography (SMR), an X-ray attenuation method employing photon counting. Repeated SMR measurements of the local mineral content of bulk samples of root dentine and a synthetic hydroxyapatite aggregate during exposure to pumped NaOCl solutions for 100 h showed no mineral loss. As predicted from apatite chemistry, reaction of NaOCl with the mineral phase can be excluded as a primary factor in changes in mechanical properties of treated dentine. Effects of retention of NaCl on endodontic sealants requires further investigation.
Mammalian stress granules (SGs) are cytoplasmic domains into which mRNAs are sorted dynamically in response to phosphorylation of eukaryotic initiation factor (eIF) 2alpha, a key regulatory step in translational initiation. The activation of one or more of the eIF2alpha kinases leads to SG assembly by decreasing the levels of eIF2-GTP-tRNA(Met), the ternary complex that is normally required for loading the initiator methionine onto the 48 S preinitiation complex to begin translation. This stress-induced scarcity of eIF2-GTP-tRNA(Met) allows the RNA-binding proteins TIA-1 (T-cell internal antigen-1) and TIAR (TIA-1-related protein) to bind the 48 S complex in lieu of the ternary complex, thereby promoting polysome disassembly and the concurrent routing of the mRNA into a SG. The actual formation of SGs occurs upon auto-aggregation of the prion-like C-termini of TIA-1 proteins; this aggregation is reversed in vivo by overexpression of the heat-shock protein (HSP) chaperone HSP70. Remarkably, HSP70 mRNA is excluded from SGs and is preferentially translated during stress, indicating that the RNA composition of the SG is selective. Moreover, the effects of HSP70 on TIA aggregation suggest a feedback loop whereby HSP70 synthesis is auto-regulated. Proteins that promote mRNA stability [e.g. HuR (Hu protein R)] and destabilize mRNA [i.e. tristetraprolin (TTP)] are also recruited to SGs, suggesting that SGs effect a process of mRNA triage, by promoting polysome disassembly and routing mRNAs to cytoplasmic domains enriched for HuR and TTP. This model reveals connections between the eIF2alpha kinase system, mRNA stability and cellular chaperone levels.
The estimation of differential renal function from dynamic renography affects clinical decisions. The estimation requires the kidneys to be delineated with regions of interest. However, in the presence of unilateral hydronephrosis it is not unusual for the affected kidney to be enlarged so that the regions of interest required to delineate the normal and abnormal kidneys are themselves dissimilar in size. The question, which then arises is, will this difference in the sizes of the regions of interest affect the resultant estimation of differential renal function? Eighteen children aged 1 month to 7 years, with prenatal ultrasound diagnosis of unilateral hydronephrosis where the affected kidney was larger than the normal kidney, underwent a total of 57 diuretic renograms using 99mTc-mercaptoacetyltriglycine. The renographic data were retrieved from optical disc and re-analysed. Regions of interest were generated which enclosed each kidney plus a region of interest of equal size to the abnormal large kidney was placed over the normal kidney. The consensus report from the Scientific Committee of Radionuclides in Nephrology described the Rutland-Patlak plot and integral methods for the estimation of differential renal function from dynamic renography. These two methods were used to analyse renal curves with and without background subtraction. Evaluation of the results suggest that technical factors, including the size of the region of interest, may affect differential renal function, and may, in part, explain the reports of the super-normal kidney in the literature.
It was reported previously that four baby hamster kidney (BHK) proteins with molecular masses of 108, 60, 50, and 42 kDa bind specifically to the 3'-terminal stem-loop of the West Nile virus minus-stand RNA [WNV 3'(-) SL RNA] (P. Y. Shi, W. Li, and M. A. Brinton, J. Virol. 70:6278-6287, 1996). In this study, p42 was purified using an RNA affinity column and identified as TIAR by peptide sequencing. A 42-kDa UV-cross-linked viral RNA-cell protein complex formed in BHK cytoplasmic extracts incubated with the WNV 3'(-) SL RNA was immunoprecipitated by anti-TIAR antibody. Both TIAR and the closely related protein TIA-1 are members of the RNA recognition motif (RRM) family of RNA binding proteins. TIA-1 also binds to the WNV 3'(-) SL RNA. The specificity of these viral RNA-cell protein interactions was demonstrated using recombinant proteins in competition gel mobility shift assays. The binding site for the WNV 3'(-) SL RNA was mapped to RRM2 on both TIAR and TIA-1. However, the dissociation constant (K(d)) for the interaction between TIAR RRM2 and the WNV 3'(-) SL RNA was 1.5 x 10(-8), while that for TIA-1 RRM2 was 1.12 x 10(-7). WNV growth was less efficient in murine TIAR knockout cell lines than in control cells. This effect was not observed for two other types of RNA viruses or two types of DNA viruses. Reconstitution of the TIAR knockout cells with TIAR increased the efficiency of WNV growth, but neither the level of TIAR nor WNV replication was as high as in control cells. These data suggest a functional role for TIAR and possibly also for TIA-1 during WNV replication.
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An in vitro study was done to test the accuracy and functionality of computer-assisted surgery in pelvic orthopaedic surgery. The study was done on two fresh hips from one cadaver. In each hip, 10 titanium marker screws were inserted through standard pelvic osteotomy incisions. After a computed tomography scan was obtained the data were introduced into the navigation system. For the accuracy measurements the location of the center of the spherical heads of the marker screws was determined relative to a reference base attached to the pelvis using a special pointer that corresponded to the spherical head of the screws. A randomized trial was done with two surgeons to test the accuracy of two different anatomy-based registration protocols. The deviation between the virtual position of the marker screws in the pelvis, calculated by the computer after each anatomy based registration, and the real position were compared for each registration. Accuracy is not only related to the distance of the computed tomography slices and the necessary computed tomography field of view but also depends on the location of the point on the pelvis.
PURPOSE: To assess the risk and patterns of second malignancy in a group of women treated with conservative surgery and radiation in a relatively contemporary manner for early-stage invasive breast cancer, and to identify a subgroup of these women at increased risk for a second cancer. METHODS AND MATERIALS: From 1978 to 1994, 1,253 women with unilateral Stage I-II breast cancer underwent wide excision, axillary dissection, and radiation. The median follow-up was 8.9 years, with 446 patients followed for >or= 10 years. The median age was 55 years. Sixty-eight percent had T1 tumors and 74% were axillary-node negative. Radiation was directed to the breast only in 78%. Adjuvant therapy consisted of chemotherapy in 19%, tamoxifen in 19%, and both in 8%. Factors analyzed for their association with the cumulative incidence of all second malignancies, contralateral breast cancer, and non-breast cancer malignancy were: age, menopausal status, race, family history, obesity, smoking, tumor size, location, histology, pathologic nodal status, region(s) treated with radiation, and the use and type of adjuvant therapy. RESULTS: One hundred seventy-six women developed a second malignancy (87 contralateral breast cancers at a median interval of 5.8 years, and 98 non-breast cancer malignancies at a median interval of 7.2 years). Nine women had both a contralateral breast cancer and non-breast cancer second malignancy. The 5- and 10-year cumulative incidences of a second malignancy were 5% and 16% for all cancers, 3% and 7% for contralateral breast cancer, 3% and 8%, for all second non-breast cancer malignancies, and 1% and 5%, respectively, for second non-breast cancer malignancies, excluding skin cancers. Patient age was a significant factor for contralateral breast cancer and non-breast cancer second malignancy. Young age was associated with an increased risk of contralateral breast cancer, while older age was associated with an increased the risk of a second non-breast cancer second malignancy. A positive family history increased the risk of contralateral breast cancer, but not non-breast cancer malignancies. The risk of a contralateral breast cancer increased as the number of affected relatives increased. Tamoxifen resulted in a nonsignificant decrease in contralateral breast cancer and an increase in non-breast cancer second malignancies. The 5-and 10-year cumulative incidences for leukemia and lung cancer were 0.08% and 0.2%, and 0.8% and 1%, respectively. There was no significant effect of chemotherapy or the regions treated with radiation on contralateral breast cancer or non-breast cancer second malignancy. The most common types of second non-breast cancer malignancies were skin cancers, followed by gynecologic malignancies (endometrial), and gastrointestinal malignancies (colorectal and pancreas). CONCLUSION: The 10-years cumulative incidence of a second cancer in this study was 16%. Young age and family history predicted for an increased risk of contralateral breast cancer, and older age predicted for an increased risk of non-breast cancer malignancy. The majority of patients treated with conservative surgery and radiation with or without adjuvant systemic therapy will not develop a second cancer. Long-term follow-up is important to document the risk and patterns of second cancer, and knowledge of this risk and the patterns will influence surveillance and prevention strategies.
o-Phthalaldehyde (OPA) is a bifunctional reagent that forms an isoindole derivative by reacting with cysteine and lysine residues separated by approximately 0.3 nm. OPA inhibits sarcoplasmic reticulum (SR) Ca(2+)-ATPase activity at low micromolar concentrations and induces Ca(2+) release from actively loaded SR vesicles by activating the ryanodine receptor from fast twitch skeletal muscle. Both ryanodine binding and single-channel activity show a biphasic concentration dependence. At low OPA concentrations (<100 microM), ryanodine binding and single channel activity are stimulated, while at higher concentrations, a time-dependent sequential activation and inhibition of receptor binding is observed. Activation is characterized by a Ca(2+)-independent increase in maximal receptor occupancy. Data are presented to support a model in which Ca(2+) channel and ryanodine binding activity are enhanced due to an intramolecular cross-linking of nearby lysine and nonhyperreactive cysteine residues. OPA complexation with endogenous lysine residue(s) is critical for receptor activation.
BACKGROUND: Tobacco smoking is associated with chronic obstructive pulmonary disease (COPD) in more than 80% of cases. Our aim was to investigate the effect of sustained-release bupropion (amfebutamone) (SR) in promoting abstinence from smoking in patients with COPD. METHODS: In a double-blind, randomised, placebo-controlled trial 404 individuals with mild or moderate COPD who smoked 15 or more cigarettes per day, were assigned bupropion SR (150 mg twice daily) or placebo for 12 weeks. All patients received smoking cessation counselling. Study medication was taken for 1 week before patients attempted to stop smoking. The primary efficacy endpoint was the complete and continuous abstinence from smoking from the beginning of week 4 to the end of week 7. Participants were followed up at month 6. Analysis was by intention to treat. FINDINGS: All patients were chronic smokers with a smoking history of about 51 pack-years. Continuous smoking abstinence rates from week 4 to 7 were significantly higher in participants receiving bupropion SR than in those receiving placebo (28% [57/204] vs 16% [32/200], p=0.003). Continuous abstinence rates from weeks 4 to 12 (18% [36/204] vs 10% [20/200]) and weeks 4 to 26 (16% [32/204] vs 9% [18/200]) were also higher in participants receiving bupropion SR than in those taking placebo (p<0.05). Furthermore, symptoms of tobacco craving and withdrawal were attenuated in those receiving bupropion SR. Seven individuals discontinued study medication because of adverse events. INTERPRETATION: Bupropion SRis a well-tolerated and effective aid to smoking cessation in people with mild to moderate COPD.
BACKGROUND: Prevention of regional and metastatic spread of cutaneous malignancies requires understanding the physiologic mechanism of tumor cell invasion. In vitro models are convenient for studying the in vitro invasive phenotype of normal cells, tumor cell lines, or genetically altered cells in a 3-dimensional matrix, but they should attempt to recapitulate the complex in vivo submucosal environment. A new acellular extracellular matrix, porcine submucosal matrix (PSM), is thought to accurately recapitulate the submucosal matrix. A novel in vitro model using PSM to assess mucocutaneous tumor cell invasion was studied. METHODS: The morphologic characteristics, growth, and invasive behavior of human head and neck squamous cell carcinoma (UM-SCC-1, UM-SCC-5, UM-SCC-17B, and OSC-19) cell lines were assessed on the PSM gel and compared with commonly used in vitro invasion models (type I collagen and Matrigel matrices). The invasive phenotype of canine kidney cells was also assessed on each matrix, because this cell line is known to demonstrate a characteristic in vitro invasive phenotype. RESULTS: The PSM-supported head and neck squamous cell carcinoma tumor cell line growth and single cell invasion were seen under stimulated conditions, similar to type I collagen gels. The invasive phenotype of canine kidney cells behaved similarly on PSM and collagen. Matrigel did not support growth well, and invasion occurred only superficially in isolated areas. CONCLUSION: The PSM is a good in vitro model for assessment of pharmacologic and genetic manipulations of head and neck squamous cell carcinoma tumor cell lines and has several advantages over other commonly used matrices.
HYPOTHESIS: Angioaccess procedures for dialysis have varied patency rates with frequent need for intervention. A superficialized arteriovenous brachiobasilic fistula created as a 2-step procedure will have good long-term patency with minimal complication. DESIGN: Retrospective medical record review and patient interview. SETTING: Tertiary referral university hospital. PATIENTS: Twelve patients who underwent delayed superficialization of brachiobasilic fistula from September 1994 to April 2000. MAIN OUTCOME MEASURES: Patency of fistula for dialysis, and major and minor complications, including revisions. RESULTS: Delayed superficialization of brachiobasilic fistula was performed in 12 patients. Fistulas have been used for a mean duration of 22.4 months (range, 10-59 months). Two patients required alternate access owing to thrombosis of brachiobasilic fistula. CONCLUSIONS: The delayed superficialized brachiobasilic arteriovenous fistula has a good initial patency rate with minimal complications. It should be considered early in patients if radiocephalic fistula is unavailable.
OBJECTIVE: Patients with systemic autoimmune diseases have been reported to have reduced numbers of peripheral blood natural killer (NK) cells compared with healthy subjects. The ability of selected cytokines to trigger NK cell death prompted us to compare the levels of peripheral blood cytokines with the numbers of NK cells in patients with various systemic autoimmune diseases. METHODS: We used enzyme-linked immunosorbent assays to measure the concentration of selected cytokines (interleukin-18 [IL-18], IL-15, IL-12, IL-2, interferon-gamma [IFNgamma], and tumor necrosis factor alpha [TNFalpha]) in sera from 58 patients with systemic autoimmune diseases and 33 healthy controls. The absolute number of T cells and NK cells in the peripheral blood was measured in parallel using flow cytometry. The ability of selected cytokines to induce NK cell death was then measured using 3,3'-dihexyloxacarbocyanine iodide dye, propidium iodide staining, and caspase 3 activity. RESULTS: Levels of IL-18, IL-15, IFNgamma, and TNFalpha were elevated in sera from patients with systemic autoimmune diseases compared with normal controls. The percentage of NK cells and natural killer T cells were significantly decreased in the peripheral blood of patients with systemic autoimmune diseases compared with normal controls. Serum concentrations of IL-18, IL-15, and TNFalpha were inversely related to the number of NK cells in both patients and healthy controls. The combination of IL-18 and IL-15 or IL-18 and IL-12 induced NK cell death in vitro. The combination of IL-18 and IL-15 or IL-18 and IL-12 enhanced IFNgamma and TNFalpha production by NK cells in vitro. Cytokine-induced NK cell death is caspase-dependent and is partially blocked by neutralizing antibodies against TNFalpha. CONCLUSION: High levels of IL-18 and IL-15 are associated with the decreased number of NK cells that is observed in patients with systemic autoimmune diseases.