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Biomedical subjects

J Hanley

Publications and source records attributed to J Hanley.

At least 19 recordsLinked to original sources
PubMed2002

Orientation selection in photosynthetic PS I multilayers: structural investigation of the charge separated state P(700)(+z.rad;)A(1)(-z.rad;) by high-field/high-frequency time-resolved EPR at 3.4 T/95 GHz.

The radical-pair state of the primary electron donor and the secondary electron acceptor (P(700)(+z.rad;)A(1)(-z.rad;)) of the photosynthetic reaction center (RC) photosystem I (PS I) of Synechocystis PCC 6803 was studied by time-resolved electron paramagnetic resonance (TREPR) at high field/high frequency (3.4 T/95 GHz) using orientation selection in multilayers. The goal of the present article is to work out the basis for future studies, in which the improved resolution of such multilayers may be used to detect mutation-induced structural changes of PS I in membrane preparations. This approach is particularly interesting for systems that cannot be prepared as single crystals. However, in order to use such multilayers for structural investigations of protein complexes, it is necessary to know their orientation distribution. PS I was chosen as a test example because the wild type was recently crystallized and its X-ray structure determined to 2.5 A resolution [Nature 411 (2001) 909]. On the basis of our experimental results we determined the orientation distribution. Furthermore, a simulation model for the general case in which the orientation distribution is not axially symmetric about the C(2) symmetry axis of the RC is developed and discussed. Spectra simulations show that changes in the TREPR spectra of PS I are much more significant for these oriented multilayers than for disordered samples. In this way the use of oriented multilayers, in conjunction with multifrequency TREPR measurements on oriented as well as on disordered samples, is a promising approach for studies of structural changes of PS I systems that are induced by point mutations.

Anisotropy↗
PubMed2002

Does a special interest in laparoscopy affect the treatment of acute cholecystitis?

BACKGROUND: We tested the hypothesis that the treatment of patients with acute cholecystitis (AC) would be improved under the care of laparoscopic specialists. METHODS: The records of patients undergoing cholecystectomy for AC from 1 January 1996 to 31 December 1998 were reviewed retrospectively. Of 170 patients, 48 were cared for by three laparoscopic specialists (LS group), whereas 122 were treated by nine general surgeons who perform only laparoscopic cholecystectomy (LC) (GS group). The rates of successful LC, complications, and length of hospital stay were compared. Multivariate analysis was used to control for baseline differences. RESULTS: The patients in the GS group were older (median age, 63 vs 53 years; p = 0.01). In all, 31 LS patients (65%), as compared with 44 GS patients (36%), had successful laparoscopic treatment (p = 0.001). The operating time was the same (median, 70 min). The proportion of patients with postoperative complications was similar in the two groups (37% in the GS vs 31% in the LS group; p = 0.6). The median postoperative hospital stay (3 vs 5 days; p <0.01) was shorter in the LS group. On logistic regression analysis, significant predictors of a successful laparoscopic operation included LS group (p <0.01) and age (p = 0). Predictors of prolonged length of hospital stay were age (p <0.01) and comorbidity score (p <0.01), with LS group status not a significant factor (p = 0.21). CONCLUSIONS: Patients with AC are more likely to undergo successful LC if cared for by a surgeon with an interest in laparoscopy. However, length of hospital stay is influenced more by patient factors in a multivariate model.

Acute Disease↗
PubMed2002

Assessment of nicotine dependence symptoms in adolescents: a comparison of five indicators.

OBJECTIVE: To examine the psychometric properties, test-retest reliability, and convergent construct validity of five indicators of nicotine dependence (ND) symptoms in adolescents. DESIGN: Analysis of baseline data from a prospective study on the natural history of ND in 1264 adolescents aged 12-13 years. SETTING: Ten Montreal high schools. SUBJECTS: 233 grade 7 students who had smoked cigarettes one or more times in the three months preceding the baseline data collection. MAIN OUTCOME MEASURES: Five indicators of ND symptoms including two that are multi-dimensional (a proxy measure of ICD-10 criteria for tobacco dependence; the Hooked on Nicotine Checklist (HONC)) and three new indicators of "symptom clusters" that emerged from principal component analysis (ND/cravings, withdrawal symptoms, self medication). RESULTS: All five indicators demonstrated acceptable internal and test-retest reliability. The correlation between the HONC and ND/cravings was 0.910. All other correlations between indicators ranged between 0.716-0.824. There was considerable overlap in the independent correlates identified for each indicator. CONCLUSIONS: All five indicators performed well psychometrically. Until the meaning, relative importance, and usefulness of each scale is clarified in longitudinal work, decisions regarding which scale(s) are most informative will depend more on the content of the scales, the need for a multi- or unidimensional indicator, and whether or not the scale is theory based.

Adolescent↗
PubMed2001

Role of acidic amino acid residues of PsaD subunit on limiting the affinity of photosystem I for ferredoxin.

The PsaD subunit of photosystem I is one of the central polypeptides for the interaction with ferredoxin, its acidic electron acceptor. In the cyanobacterium Synechocystis 6803, this role is partly performed by a sequence extending approximately from histidine 97 to arginine 119, close to the C-terminus. In the present work, acidic amino acids D100, E105, and E109 are shown to moderate the affinity of Photosystem I for ferredoxin. Most single replacements of these residues by neutral amino acids increased the affinity for ferredoxin, resulting in a dissociation constant as low as 0.015 microM for the E105Q mutant (wild-type K(D) = 0.4 microM). This is the first report on the limitation of photosystem I affinity for ferredoxin due to acidic amino acids from PsaD subunit. It highlights the occurrence of a negative control on the binding during the formation of transient complexes between electron carriers.

Amino Acid Sequence↗
PubMed2001

Waiting time for breast cancer surgery in Quebec.

BACKGROUND: Currently there is no agreement on the optimal time to treatment of breast cancer; however, given the considerable emphasis on early detection, one would expect a similar emphasis on early treatment. The purpose of our study was to assess the time interval to surgery from initiation of diagnosis among Quebec women with breast cancer and to examine the influence on waiting time of age, pattern of care and cancer stage. METHODS: Records of physician fee-for-service claims and of hospital admissions were obtained for all Quebec women who underwent an invasive procedure for the diagnosis or treatment of breast cancer between 1992 and 1998. Waiting time was calculated as the number of days between the first diagnostic procedure and surgical treatment. RESULTS: There were 29,606 episodes of breast cancer surgery among 28,100 women: 5922 mastectomies and 23,684 lumpectomies. The absolute number of episodes of breast cancer treated with surgery rose from 3626 in 1992 to 5162 in 1998. The overall median waiting time was 34 days (interquartile range [IQR] 19-62); 13.5% of the women waited longer than 90 days. The median waiting time rose from 29 days (IQR 15-54) in 1992 to 42 days (IQR 24-72) in 1998, representing a relative increase of 37% (95% confidence interval [CI] 32%-43%) after adjusting for age and cancer stage. The median waiting time increased with the number of diagnostic procedures, from 24 days (IQR 14-42) with 1 procedure to 48 days (IQR 27-84) with 3 procedures to 72 days (IQR 43-121) with 4 procedures, representing adjusted relative increases of 97% (95% CI 91%-103%) and 194% (95% CI 181%-208%), respectively. The proportion of women receiving 3 or more diagnostic procedures before surgery increased steadily over the study period, from 19.2% in 1992 to 33.0% in 1998. The median waiting time was shorter with more advanced stages of cancer: 53 days (IQR 30-86) for carcinoma in situ, 35 (IQR 20-62) for localized disease, 28 (IQR 16-49) for regional disease and 24 (IQR 11-52) for disseminated disease. INTERPRETATION: Waiting time between initial diagnosis and first surgery for breast cancer has increased substantially in Quebec between 1992 and 1998. Possible explanations include increased demand, decreased resources and changes in patterns of care.

Adult↗
PubMed2001

Quantifying and reducing the risk of bloodborne pathogen exposure.

The risk of becoming infected with bloodborne pathogens (e.g., hepatitis B, hepatitis C, HIV) during surgery is real. The degree of risk for perioperative personnel is related to factors that include participating in large numbers of surgical procedures each year; the nature of perioperative work (e.g., use of different types of sharp instruments): exposure to large amounts of blood and body fluids; the prevalence of bloodborne pathogens in the surgical population; the variation in different organisms' ability to be transmitted; the existence of vaccines and the level of vaccination; the availability of postexposure treatment; and the consequences of acquiring the disease. Controlling risks to perioperative personnel can be accomplished by using the Occupational Safety and Health Administration's three methods of control--redesigning surgical equipment and procedures, changing work practices, and enhancing the personal protection equipment of perioperative personnel.

Blood-Borne Pathogens↗
PubMed2001

Multiple functions for the C terminus of the PsaD subunit in the cyanobacterial photosystem I complex.

PsaD subunit of Synechocystis sp PCC 6803 photosystem I (PSI) plays a critical role in the stability of the complex and is part of the docking site for ferredoxin (Fd). In the present study we describe major physiological and biochemical effects resulting from mutations in the accessible C-terminal end of the protein. Four basic residues were mutated: R111, K117, K131, and K135, and a large 36-amino acid deletion was generated at the C terminus. PSI from R111C mutant has a 5-fold decreased affinity for Fd, comparable with the effect of the C terminus deletion, and NADP+ is photoreduced with a 2-fold decreased rate, without consequence on cell growth. The K117A mutation has no effect on the affinity for Fd, but decreases the stability of PsaE subunit, a loss of stability also observed in R111C and the deletion mutants. The double mutation K131A/K135A does not change Fd binding and reduction, but decreases the overall stability of PSI and impairs the cell growth at temperatures above 30 degrees C. Three mutants, R111C, K117A, and the C-terminal deleted exhibit a higher content of the trimeric form of PSI, in apparent relation to the removal of solvent accessible positive charges. Various regions in the C terminus of cyanobacterial PsaD thus are involved in Fd strong binding, PSI stability, and accumulation of trimeric PSI.

Cyanobacteria↗
PubMed2000

Orientation of the Mn(II)-Mn(III) dimer which results from the reduction of the oxygen-evolving complex of photosystem II by NO: an electron paramagnetic resonance study.

The central part of the oxygen-evolving complex of photosystem II is a cluster of four manganese atoms. The known EPR spectra in the various oxidation states of the cluster are complicated by the magnetic interactions of the four Mn ions and accordingly are difficult to analyze. It has been shown recently that NO at -30 degrees C slowly reduces the cluster to a Mn(II)-Mn(III) state [Sarrou, J., Ioannidis, N., Deligiannakis, Y., and Petrouleas, V. (1998) Biochemistry 37, 3581-3587). We study herein the orientation dependence of the Mn(II)-Mn(III) EPR spectrum with respect to the thylakoid membrane plane. Both the powder and the oriented spectra are satisfactorily simulated with the same set of fine and hyperfine parameters assuming axial symmetry and collinear g and A tensors. The axial component of the tensors is found to be oriented at an angle of 20 degrees +/- 10 degrees to the membrane plane normal (mosaic spread Omega = 40 degrees ). We make the reasonable assumption that the Mn(II)-Mn(III) dimer is one of the di-mu-oxo units that has been suggested to comprise the Mn tetramer. On the basis of the sign of the hyperfine tensor anisotropy, the axial direction is assigned to the d(z(2)) orbital of Mn(III), which by comparison with synthetic model complexes is assumed to be oriented perpendicular to the Mn-(mu-oxo)-Mn plane. The present results complement earlier orientation studies by EXAFS and suggest that the Mn-(mu-oxo)-Mn plane makes a small angle (approximately 20 degrees) with the membrane plane and the axis connecting the bridging oxygens is approximately parallel to the plane.

Manganese↗
PubMed2000

Technical aspects of the deep inspiration breath-hold technique in the treatment of thoracic cancer.

PURPOSE: The goal of this paper is to describe our initial experience with the deep inspiration breath-hold (DIBH) technique in conformal treatment of non-small-cell lung cancer with particular emphasis on the technical aspects required for implementation. METHODS AND MATERIALS: In the DIBH technique, the patient is verbally coached through a modified slow vital capacity maneuver and brought to a reproducible deep inspiration breath-hold level. The goal is to immobilize the tumor and to expand normal lung out of the high-dose region. A physicist or therapist monitors and records patient breathing during simulation, verification, and treatment using a spirometer with a custom computer interface. Examination of internal anatomy during fluoroscopy over multiple breath holds establishes the reproducibility of the DIBH maneuver for each patient. A reference free-breathing CT scan and DIBH planning scan are obtained. To provide an estimate of tumor motion during normal tidal breathing, additional scan sets are obtained at end inspiration and end expiration. These are also used to set the spirometer action levels for treatment. Patient lung inflation is independently verified over the course of treatment by comparing the distance from the isocenter to the diaphragm measured from the DIBH digitally reconstructed radiographs to the distance measured on the portal films. Patient breathing traces obtained during treatment were examined retrospectively to assess the reproducibility of the technique. RESULTS: Data from the first 7 patients, encompassing over 250 treatments, were analyzed. The inferred displacement of the centroid of gross tumor volume from its position in the planning scan, as calculated from the spirometer records in over 350 breath holds was 0.02 +/- 0.14 cm (mean and standard deviation). These data are consistent with the displacements of the diaphragm (-0.1 +/- 0.4 cm; range, from -1.2 to 1.1 cm) relative to the isocenter, as measured on the (92) portal films. The latter measurements include the patient setup error. The patient averaged displacement of the tumor during free breathing, determined from the tumor displacement between end inspiration and end expiration, was 0.8 +/- 0.5 cm in both the superior-inferior and anterior-posterior directions and 0.1 cm (+/- 0.1 cm) medial-laterally. CONCLUSION: Treatment of patients with the DIBH technique is feasible in a clinical setting. With this technique, consistent lung inflation levels are achieved in patients, as judged by both spirometry and verification films. Breathing-induced tumor motion is significantly reduced using DIBH compared to free breathing, enabling better target coverage.

Carcinoma, Non-Small-Cell Lung↗
PubMed2000

The deep inspiration breath-hold technique in the treatment of inoperable non-small-cell lung cancer.

PURPOSE: Conventional radiotherapeutic techniques are associated with lung toxicity that limits the treatment dose. Motion of the tumor during treatment requires the use of large safety margins that affect the feasibility of treatment. To address the control of tumor motion and decrease the volume of normal lung irradiated, we investigated the use of three-dimensional conformal radiation therapy (3D-CRT) in conjunction with the deep inspiration breath-hold (DIBH) technique. METHODS AND MATERIALS: In the DIBH technique, the patient is initially maintained at quiet tidal breathing, followed by a deep inspiration, a deep expiration, a second deep inspiration, and breath-hold. At this point the patient is at approximately 100% vital capacity, and simulation, verification, and treatment take place during this phase of breath-holding. RESULTS: Seven patients have received a total of 164 treatment sessions and have tolerated the technique well. The estimated normal tissue complication probabilities decreased in all patients at their prescribed dose when compared to free breathing. The dose to which patients could be treated with DIBH increased on average from 69.4 Gy to 87.9 Gy, without increasing the risk of toxicity. CONCLUSIONS: The DIBH technique provides an advantage to conventional free-breathing treatment by decreasing lung density, reducing normal safety margins, and enabling more accurate treatment. These improvements contribute to the effective exclusion of normal lung tissue from the high-dose region and permit the use of higher treatment doses without increased risks of toxicity.

Carcinoma, Non-Small-Cell Lung↗
PubMed2000

Women and cardiovascular disease.

Cardiovascular disease remains the number one killer in the United States. The face of the person with cardiovascular disease is changing. No longer is the middle-aged man at highest risk. Current data reveal that women, especially postmenopausal women, are at highest risk for cardiovascular disease. This article identifies the differences noted between men and women with cardiovascular disease, including effects in presentation, identification, and treatment.

Clinical Trials as Topic↗
PubMed1999

Deep inspiration breath-hold technique for lung tumors: the potential value of target immobilization and reduced lung density in dose escalation.

PURPOSE/OBJECTIVE: This study evaluates the dosimetric benefits and feasibility of a deep inspiration breath-hold (DIBH) technique in the treatment of lung tumors. The technique has two distinct features--deep inspiration, which reduces lung density, and breath-hold, which immobilizes lung tumors, thereby allowing for reduced margins. Both of these properties can potentially reduce the amount of normal lung tissue in the high-dose region, thus reducing morbidity and improving the possibility of dose escalation. METHODS AND MATERIALS: Five patients treated for non-small cell lung carcinoma (Stage IIA-IIIB) received computed tomography (CT) scans under 4 respiration conditions: free-breathing, DIBH, shallow inspiration breath-hold, and shallow expiration breath-hold. The free-breathing and DIBH scans were used to generate 3-dimensional conformal treatment plans for comparison, while the shallow inspiration and expiration scans determined the extent of tumor motion under free-breathing conditions. To acquire the breath-hold scans, the patients are brought to reproducible respiration levels using spirometry, and for DIBH, modified slow vital capacity maneuvers. Planning target volumes (PTVs) for free-breathing plans included a margin for setup error (0.75 cm) plus a margin equal to the extent of tumor motion due to respiration (1-2 cm). Planning target volumes for DIBH plans included the same margin for setup error, with a reduced margin for residual uncertainty in tumor position (0.2-0.5 cm) as determined from repeat fluoroscopic movies. To simulate the effects of respiration-gated treatments and estimate the role of target immobilization alone (i.e., without the benefit of reduced lung density), a third plan is generated from the free-breathing scan using a PTV with the same margins as for DIBH plans. RESULTS: The treatment plan comparison suggests that, on average, the DIBH technique can reduce the volume of lung receiving more than 25 Gy by 30% compared to free-breathing plans, while respiration gating can reduce the volume by 18%. The DIBH maneuver was found to be highly reproducible, with intra breath-hold reproducibility of 1.0 (+/- 0.9) mm and inter breath-hold reproducibility of 2.5 (+/- 1.6) mm, as determined from diaphragm position. Patients were able to perform 10-13 breath-holds in one session, with a comfortable breath-hold duration of 12-16 s. CONCLUSION: Patients tolerate DIBH maneuvers well and can perform them in a highly reproducible fashion. Compared to conventional free-breathing treatment, the DIBH technique benefits from reduced margins, as a result of the suppressed target motion, as well as a decreased lung density; both contribute to moving normal lung tissue out of the high-dose region. Because less normal lung tissue is irradiated to high dose, the possibility for dose escalation is significantly improved.

Aged↗
PubMed1999

Carotenoid oxidation in photosystem II.

The oxidation of carotenoid upon illumination at low temperature has been studied in Mn-depleted photosystem II (PSII) using EPR and electronic absorption spectroscopy. Illumination of PSII at 20 K results in carotenoid cation radical (Car+*) formation in essentially all of the centers. When a sample which was preilluminated at 20 K was warmed in darkness to 120 K, Car+* was replaced by a chlorophyll cation radical. This suggests that carotenoid functions as an electron carrier between P680, the photooxidizable chlorophyll in PSII, and ChlZ, the monomeric chlorophyll which acts as a secondary electron donor under some conditions. By correlating with the absorption spectra at different temperatures, specific EPR signals from Car+* and ChlZ+* are distinguished in terms of their g-values and widths. When cytochrome b559 (Cyt b559) is prereduced, illumination at 20 K results in the oxidation of Cyt b559 without the prior formation of a stable Car+*. Although these results can be reconciled with a linear pathway, they are more straightforwardly explained in terms of a branched electron-transfer pathway, where Car is a direct electron donor to P680(+), while Cyt b559 and ChlZ are both capable of donating electrons to Car+*, and where the ChlZ donates electrons when Cyt b559 is oxidized prior to illumination. These results have significant repercussions on the current thinking concerning the protective role of the Cyt b559/ChlZ electron-transfer pathways and on structural models of PSII.

Carotenoids↗
PubMed1999

Colorectal cancer prevention by non-steroidal anti-inflammatory drugs: effects of dosage and timing.

Epidemiological studies show that non-steroidal anti-inflammatory drugs (NSAIDs) reduce colorectal cancer incidence. We measured the rate ratio for colorectal adenocarcinoma according to dosage and the timing of exposure by means of a case-control study, nested in a non-concurrent cohort linkage study, using the population of beneficiaries of the Saskatchewan Prescription Drug Plan from 1981 to 1995 with no history of cancer since 1970 as the source population. Four controls per case, matched on age and gender and alive when the case was diagnosed, were randomly selected. Dispensing rates, calculated over successive time periods, characterized NSAID exposure. We accrued 3844 cases of colon cancer and 1971 cases of rectal cancer. For colon cancer a significant trend towards a decreasing rate ratio was associated with increasing exposure during the 6 months preceding diagnosis (P-trend = 0.002). For both cancers, significant trends were associated with exposure 11-15 years before diagnosis (colon: P-trend = 0.01; rectum: P-trend = 0.0001). At the highest exposure levels the rate ratio for colon cancer was 0.57 (95% confidence interval (CI) 0.36-0.89); for rectal cancer it was 0.26 (95% CI 0.11-0.61). No protection was associated with exposure during other periods. The timing of NSAID use must be considered in planning intervention trials to prevent colorectal cancer. There may be a 10-year delay before any preventive effect will appear.

Aged↗
PubMed1999

The characteristics of false negative cervical smears--implications for the UK cervical cancer screening programme.

OBJECTIVE: To accurately determine whether there are any features of an abnormal cervical smear that predispose to the production of a false negative report, in order to gain insight into why false negative reports are issued, and to establish whether there are steps that can be taken to reduce them. DESIGN: A quantitative retrospective analysis using the AxioHOME microscope of the number, size, and spatial distribution of abnormal cells in a set of 50 slides comprising a mixture of false negative and true positive cervical smears. SETTING: Five different cytology laboratories in the United Kingdom. RESULTS: False negative smears were found to be quantitatively different from true positive smears. They contained significantly fewer abnormal cells (median number of abnormal cells for false negatives = 173, median number of abnormal cells for true positives = 1712; p < 0.004), and these were more likely to be unevenly distributed on the slide. It was possible to predict with a high degree of accuracy whether a smear was a false negative by analysing number and distribution alone (kappa = 0.57). CONCLUSIONS: False negatives are quantitatively different from true positive cervical smears. This has important implications for quality assurance in the UK cervical screening programme. More consideration needs to be given to the effectiveness of existing quality assurance measures, which need to be tailored to the preferential detection of this type of abnormal cervical smear.

Cell Count↗
PubMed1998

Spin-lattice relaxation of the phyllosemiquinone radical of photosystem I.

The spin-lattice relaxation time (T1) of the phyllosemiquinone anion radical, A1-, of the photosystem I (PSI) reaction center, were measured between 4.5 and 85 K by electron spin-echo spectroscopy. The selective removal of the iron-sulfur centers, FA, FB, and FX, from PSI allowed the measurement of the intrinsic T1 of the A1- radical. The temperature dependence of the intrinsic (T1)-1 for A1- was found to be approximately T1.3 +/- 0.1. The spin-lattice relaxation of the reduced form of iron-sulfur center FX was also measured at low temperatures, in FA/FB-depleted PSI membranes. It was found that the fast-relaxing FX center enhances the spin-lattice relaxation of the phyllosemiquinone due to dipolar coupling. The effect of the reduced forms of FA/FB on the T1 of the phyllosemiquinone was minor compared to the effect of FX. By analyzing the data with a dipolar model in the light of limitations imposed by other information present in the literature, the distance between the phyllosemiquinone and FX in PSI is estimated to be 14.8 +/- 4 A.

Benzoquinones↗