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B Cronin

Publications and source records attributed to B Cronin.

17 recordsLinked to original sources

The role of pisigma* excited states in the photodissociation of heteroaromatic molecules.

High-resolution measurements of the kinetic energies of hydrogen atom fragments formed during ultraviolet photolysis of imidazole, pyrrole, and phenol in the gas phase confirm that N(O)-H bond fission is an important nonradiative decay process from their respective 1pisigma* excited states. The measurements also reveal that the respective cofragments (imidazolyl, pyrrolyl, and phenoxyl) are formed in very limited subsets of their available vibrational states. Identification of these product states yields uniquely detailed insights into the vibronic couplings involved in the photoinduced evolution from parent molecule to ultimate fragments.

Journal Article↗

High resolution photofragment translational spectroscopy of the near UV photolysis of indole: dissociation via the 1pi sigma* state.

The fragmentation dynamics of indole molecules following excitation at 193.3 nm, and at a number of different wavelengths in the range 240 < or = lambda(phot) < or = 286 nm, have been investigated by H Rydberg atom photofragment translational spectroscopy. The longer wavelength measurements have been complemented by measurements of excitation spectra for forming parent and fragment ions by two (or more) photon ionisation processes. Analysis identifies at least three distinct contributions to the observed H atom yield, two of which are attributable to dissociation of indole following radiationless transfer from the 1pi pi* excited states (traditionally labelled 1L(b) and 1L(a)) prepared by UV single photon absorption. The structured channel evident in total kinetic energy release (TKER) spectra recorded at lambda(phot) < or = 263 nm is rationalised in terms of N-H bond fission following initial pi* <-- pi excitation and subsequent coupling to the 1pi sigma* potential energy surface via a conical intersection between the respective surfaces--thereby validating recent theoretical predictions regarding the importance of this process (Sobolewski et al., Phys. Chem. Chem. Phys., 2002, 4, 1093). Analysis provides an upper limit for the N-H bond strength in indole: D0(H-indolyl) < or = 31,900 cm(-1). Unimolecular decay of highly vibrationally excited ground state molecules formed by internal conversion from the initially prepared 1pi pi* states is a source of (slow) H atoms but their contribution to the TKER spectra measured in the present work is dwarfed by that from H atoms generated by one or more (unintended but unavoidable) multiphoton processes.

Computer Simulation↗

Quantification of skeletal kinetic indices in Paget's disease using dynamic 18F-fluoride positron emission tomography.

The purpose of this study was to quantify indices of regional bone metabolism in Paget's disease and to compare these indices with normal bone using dynamic 18F-fluoride positron emission tomography (PET). Seven patients with vertebral Paget's disease had 1 h dynamic 18F-fluoride PET scans performed. The scans included a diseased vertebra and an adjacent normal vertebra. Arterial plasma input functions were also measured. A three-compartment, four-parameter model was used with nonlinear regression analysis to estimate bone kinetic variables. Compared with normal bone, pagetic bone demonstrated higher values of plasma clearance to bone mineral (Ki; 1.03 x 10(-1) vs. 0.36 x 10(-1) ml/min per milliliter; p = 0.018) and clearance to total bone tissue (K1; 2.38 x 10(-1) vs. 1.25 x 10(-1) ml/min per milliliter; p = 0.018), reflecting increased mineralization and blood flow, respectively. Release of 18F-fluoride from bone mineral (k4) was lower in pagetic bone (p = 0.022), suggesting tighter binding of 18F-fluoride to bone mineral. The notional volume of the extravascular bone compartment (K1/k2) was greater in pagetic bone (p = 0.018). Although the unidirectional extraction efficiency from the extravascular space to bone mineral (Ki/K1) was greater in pagetic bone (p = 0.018), a lower pagetic value of k2 (p = 0.028), describing the rate of transfer from the bone extravascular compartment to plasma, suggests that the 18F-fluoride that enters the relatively fibrotic marrow space of pagetic bone may be less accessible for return to plasma. These findings confirm some of the known pathophysiology of Paget's disease, introduce some new observations, and show how dynamic 18F-fluoride PET may be of value in the measurement of regional metabolic parameters in focal bone disorders.

Aged↗

Are restrictions to behaviour of patients required following fluorine-18 fluorodeoxyglucose positron emission tomographic studies?

The clinical use of positron emission tomography (PET) is expanding rapidly in most European countries. It is likely therefore that patients receiving the tracer fluorine-18 fluorodeoxyglucose (18FDG) will be discharged to come into contact with family members, members of the public and ward staff. There are few direct measurements on which to base any recommendations with regard to radiation protection, and so we have measured the dose rates from patients undergoing clinical PET examinations in our centre. Seventy-five patients who underwent whole-body and brain 18FDG PET examinations were studied. Dose rates were measured at 0.1, 0.5, 1.0 and 2.0 m from the mid thorax on leaving the department. The median administered activity was 323 MBq with a 95th percentile value of 360 MBq. The median dose rates measured at the four distances were 90.0, 35.0, 14.0 and 5.0 microSv h-1 (the median dose rates per unit administered activity at 2 h post injection were 0.31, 0.11, 0.04 and 0.02 microSv h-1 MBq-1). The corresponding 95th percentile values were 174.0, 69.0, 29.0 and 7.5 microSv h-1 (0.43, 0.2, 0.08 and 0.03 microSv h-1 MBq-1). A number of social situations were modelled and an annual dose limit of 1 mSv was used to determine whether restrictive behavioural advice was required. In the case of nursing staff on wards a value of 6 mSv was regarded as the annual limit, which translates to a daily limit of approximately 24 microSv. There is no need for restrictive advice for patients travelling by public or private transport when they leave the department 2 h after the administration of 18FDG. Similarly, there is no need for restrictive advice with regard to their contact with partners, work colleagues or children of any age, although it should be stressed that children should not accompany the patient to the scanning department. The only possible area of concern is in an oncology ward, where patients may be regularly referred for PET investigations and other high activity radionuclide studies and are partially helpless. Even in this area, however, it is unlikely that a nurse would receive a daily dose of more than 24 microSv. We conclude that there is no need for restrictive advice for patients undergoing 18FDG PET studies given the current administered activities.

Adolescent↗

Noninvasive monitoring of tumor metabolism using fluorodeoxyglucose and positron emission tomography in colorectal cancer liver metastases: correlation with tumor response to fluorouracil.

PURPOSE: To investigate and measure the metabolism of colorectal cancer liver metastases using 18F-fluorodeoxyglucose positron emission tomography (FDG PET), before and during the first month of chemotherapy. The findings were compared with tumor outcome conventionally assessed using changes in tumor size. PATIENTS AND METHODS: Patients with colorectal cancer liver metastases were treated with fluorouracil (5FU) as a protracted venous infusion (300 mg/m2/d), with or without interferon-alpha 2b for two 10-week blocks separated by a 2-week break. Before and at 1 to 2 and 4 to 5 weeks on treatment, FDG PET scans were performed. Patients fasted, were injected intravenously with FDG (50 to 100 MBq), and scanned using a large-area positron camera; the image data was processed such that regions of interest could be identified. The results were expressed as a ratio of FDG uptake in the tumor and normal liver (T:L) or as a semiquantitative standardized uptake value (SUV). These measures were compared with the tumor dimensions measured on a computed tomographic (CT) scan performed at 12 weeks from commencement of chemotherapy. RESULTS: Twenty patients were studied; however, two did not have assessable liver metastases. Objective partial responses were observed in 11 of 18 patients. A total of 27 metastatic lesions were assessable. Pretreatment T:L ratios and SUVs did not correlate with tumor response, although response was associated with lower 1- to 2-week (1.84 v 2.17; t=2.667; P < .02) and 4- to 5-week (1.36 v 2.28; t=5.02; P < .001) T:L ratios, and 4- to 5-week (3.57 v 4.95; t=2.492; P < .05) SUVs. Expressed as a percent of the baseline values of the T:L ratio, responding lesions had a greater reduction in metabolism (67% v 99%; t=7.53; P < .001). The 4- to 5-week T:L ratio was able to discriminate response from nonresponse both in a lesion-by-lesion and overall patient response assessment (sensitivity 100%; specificity 90% and 75%, respectively). CONCLUSION: Positron emission tomography used to evaluate the uptake of FDG in tumors yields data that correlate with the antitumor effect of chemotherapy in patients with liver metastases from colorectal cancer.

Antimetabolites, Antineoplastic↗

Blood flow measurement in extremity soft tissue sarcoma with technetium-99m hexamethyl-propyleneamineoxime and single photon emission computed tomography.

Blood flow measurements were made in 28 patients with soft tissue sarcoma of the extremities to investigate the prognostic significance of tumour vascularity. Four patients with benign tumours also underwent blood flow measurement. Mean and maximum tumour blood flow was calculated from technetium-99m hexamethyl-propyleneamineoxime uptake measured using single photon emission computed tomography (SPECT), tumour volume measured from SPECT transaxial image reconstructions and cardiac output assessed with Doppler ultrasonography. Twenty-seven malignant lesions and one benign tumour showed increased uptake of isotope relative to surrounding tissues. Mean sarcoma blood flow varied between 1 and 33 ml per 100 ml tumour per min, and maximum flow between 5 and 57 ml per 100 ml per min. Fourteen patients developed progressive disease during the first year of follow-up. Eight of 11 patients with a high isotope uptake ratio, eight of 12 with a high mean blood flow and eight of 14 with a high maximum blood flow relative to the respective medians for the series showed disease progression.

Adult↗

Quantitative single-photon emission tomography for tumour blood flow measurement in bronchial carcinoma.

A single-photon emission tomography (SPET) technique for the absolute measurement of tumour perfusion is described. Phantom studies have shown that source-background ratios are dependent upon source size and radial position within the phantom. A means of correcting source-background count ratios for these variables has been developed and used to correct tumour-lung ratios obtained in 28 patients with bronchial carcinomas who underwent technetium-99m hexamethylpropyleneamine oxime (99mTc-HMPAO) SPET. On SPET images, the normal lung appears as a relatively homogeneous background. The relationship between 99mTc background concentration (kBq/ml) and counts/pixel was determined from phantom studies and the tumour 99mTc concentration from the background 99mTc concentration and corrected tumour-lung ratio. The total activity of the lipophilic 99mTc-HMPAO species injected was measured. The activity reaching the systemic circulation (Asys) was obtained by subtracting the activity trapped in the pulmonary circulation (obtained from background 99mTc concentration and lung volume). Tumour blood flow may then be calculated from fraction of Asys contained in the tumour provided cardiac output and extraction fraction are known. Blood flow through the central region of tumours ranged from zero to 59.0 (mean 14.1) ml min-1 100 g-1 and through the whole tumour from 0.6 to 68.0 (mean 20.6) ml min-1 100 g-1.

Blood Flow Velocity↗

Anatomically derived attenuation coefficients for use in quantitative single photon emission tomography studies of the thorax.

Elimination of errors due to poor attenuation correction is an essential part of any quantitative single photon emission tomography (SPET) technique. Attenuation coefficients (mu Tc) for use in attenuation correction of SPET data were determined using technetium 99m and cobalt 57 flood sources and using topographical information obtained from computed tomography (CT) scans and magnetic resonance (MR) images. In patients with carcinoma of the bronchus, the mean attenuation coefficient for 99mTc was 0.096 cm-1 when determined across a transverse section of the thorax at the level of the tumour by means of a 57Co flood source (13 patients) and 0.093 and 0.074 cm-1 as determined from CT scans for points in the centre of the tumour and contralateral normal lung, respectively (21 patients). In 18 patients with breast tumours, the mean attenuation coefficient for 99mTc was 0.110 and 0.076 cm-1 when determined from MRI cross-sections for points in the centre of the tumour and normal contralateral lung, respectively. This indicates significant overcorrection for attenuation when the conventional value of 0.12 cm-1 is used. A value in the range 0.08-0.09 cm-1 would be more appropriate for SPET studies of the thorax. An alternative approach to quantitative region of interest (ROI) analysis is to perform attenuation correction appropriate to the centre of each ROI (using topographical information derived from CT or MRI) on non-attenuation-corrected reconstructions.

Breast Neoplasms↗

The effects of single dose oral hydralazine on blood flow through human lung tumours.

Hydralazine has been shown to reduce tumour blood flow and to potentiate the cytotoxicity of melphalan and bioreductive agents in mice. In order to determine whether such a strategy might have clinical potential, a study was undertaken to investigate the effects of hydralazine on blood flow through human tumours. Twenty-two patients with carcinoma of the bronchus received a single oral dose of hydralazine in the range 25 to 150 mg (0.37-2.86 mg/kg) according to age and acetylator status. Tumour blood flow was assessed by single photon emission computed tomography (SPECT) performed 10 min following intravenous 99Tcm-HMPAO on two occasions 2-8 days apart, the second being performed 60 min after hydralazine administration. In 20 evaluable patients, hydralazine caused a 38% increase in blood flow through the whole tumour (p = 0.007) and a 28% increase in flow through the tumour centre (p = 0.03) with greater increases occurring in patients sustaining greater falls in peripheral resistance. Tumour vascular resistance fell indicating active vasodilation in arterioles supplying tumours. Side-effects due to hydralazine were reported by eight patients.

Administration, Oral↗

Technetium-99m HMPAO and SPECT in the assessment of blood flow in human lung tumours.

In order to assess the blood flow patterns through human lung tumours, 20 patients received 400-750 MBq 99TcmHMPAO intravenously 10 min before single photon emission computed tomography (SPECT). Ratios of uptake in the whole tumour relative to normal lung ranged from 0.35 to 1.53 (mean 1.01) with eight tumours showing less uptake than normal lung and ten showing greater uptake. In one patient the tumour was not distinguishable from surrounding lung and in another a large pleural effusion prevented evaluation. Tumour: lung ratios for central tumour regions ranged from 0 to 1.83 (mean 0.80) with 13 showing lower uptake than normal lung and five showing greater uptake. Duplicate scans were performed in eight patients demonstrating satisfactory reproducibility. This technique provides a simple and reproducible method for the assessment of tumour blood flow.

Adult↗

99Tcm-labelled meso-HMPAO and glutathione content of human lung tumours.

Levels of reduced glutathione (GSH) are increased in some types of malignant tumours and are known to influence the response to radio- and chemotherapy. In vitro studies suggest a correlation between cellular GSH concentration and retention of the meso form of hexamethyl propyleneamineoxime (HMPAO). This study investigates the relationship between in vivo tissue retention of 99Tcm-labelled HMPAO and GSH concentration in ten patients referred for thoracotomy for possible lung cancer. Retention of 99Tcm-HMPAO was measured using single photon emission computed tomography (SPECT). The tumour and normal lung concentration of reduced glutathione (GSH) was measured in tissue specimens collected peroperatively. Malignancy was confirmed in eight patients. Of seven patients undergoing curative resection for carcinoma, tumour GSH concentration was higher (mean 2.76 mM) than normal lung (mean 1.04 mM). In one neurofibroma, the GSH concentration was 1.80 mM. No correlation was found between 99Tcm meso-HMPAO retention and either the tumour GSH concentration or the tumour:lung GSH ratio. The results from this small series demonstrate that the intracellular GSH concentration of malignant lung tumours is generally higher than that in normal lung but that meso-HMPAO retention could not be used to predict these levels.

Carcinoma, Non-Small-Cell Lung↗

Functions of the two adenovirus early E1A proteins and their conserved domains in cell cycle alteration, actin reorganization, and gene activation in rat cells.

Rat embryo cells were infected with adenovirus type 5 mutants that code for only one of the two early E1A proteins, mutants with defects in one of the two conserved regions common to the two proteins, or mutants with defects in the 46-amino-acid region unique to the 289-amino-acid E1A protein. Cells were scored for altered cell cycle progression, disruption of actin stress fibers, and activation of E2A expression. Mutants lacking either E1A protein were able to cause all of these effects; but mutants lacking a 243-amino-acid protein had less effect, and mutants lacking a 289-amino-acid protein much less effect, than wild-type virus. A mutation in any of the three conserved regions caused a defect in each E1A effect. To investigate the reported function of conserved domain 2 in mitosis, we monitored by fluorescence-activated cell sorter the reduction in Hoechst 33342 fluorescence that occurs when cells divide after undergoing a round of DNA replication in 5-bromodeoxyuridine. A smaller percentage of adenovirus-infected cells than mock-infected cells divided within a given period after completing a round of DNA replication. Viruses with mutations in conserved domain 2 were defective for initiation of cellular DNA replication, as were all other E1A mutants we have examined, but had no specific defect in cell division compared with wild-type virus. Thus, although there may be some specialization of function between the two E1A proteins and between their conserved domains, it was not apparent in the aspects of E1A function and the mutants that we examined.

Actin Cytoskeleton↗