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PubMed1991

Ewing's sarcoma: local tumor control and patterns of failure following limited-volume radiation therapy.

Sixty children with localized osseous Ewing's sarcoma were treated between 1978 and 1988 with induction chemotherapy (cyclophosphamide, adriamycin), irradiation and/or surgery, and 10 months of maintenance chemotherapy (cyclophosphamide, adriamycin, dactinomycin, vincristine). Following induction chemotherapy, 43 patients received primary radiation therapy to limited radiation volumes defined by post-chemotherapy residual soft tissue tumor extension and initial osseous tumor extent. Irradiation was defined as low dose at 30-36 Gy (median 35 Gy) for 31 cases with objective response to induction chemotherapy and high dose at 50-60 Gy (median 50.4 Gy) for 12 patients with poor response to induction chemotherapy or with tumors greater than or equal to 8 cm. Overall event-free survival at 5 years is 59% and local tumor control is 68%. Initial failures have been local (12), simultaneous local and distant failures (7), and distant (6). In the surgical resection group, 14 patients had complete resection without radiation therapy, and 3 patients had microscopic residual plus 35-41 Gy; 100% local control has been maintained. In 43 patients with primary radiation therapy group, local tumor control is 58% (p = .004). Despite limited radiation volume, 18/19 local failures occurred centrally within the bone, well within the radiation volume. Imaging response to induction chemotherapy predicted local tumor control in the radiation therapy group: 62% with complete response/partial response versus 17% with no response/progressive disease (p less than 0.01). Local tumor control related strongly to primary tumor size in the radiation therapy group; among 31 cases receiving 35 Gy, local tumor control is 90% for lesions less than 8 cm versus 52% for tumors greater than or equal to 8 cm (p = .054). The central pattern of local failure in this experience suggests the effectiveness of limited radiation volume. The overall local tumor control rate following the tested dose level of 35 Gy appears to be inadequate, although results in selected cases with tumors less than 8 cm in greatest tumor dimension indicate potential efficacy in a yet limited experience.

Adolescent↗
PubMed1994

Time-dose relationship for local tumor control following alternate week concomitant radiation and chemotherapy of advanced head and neck cancer.

PURPOSE: To analyze the time-dose relationship for local control of disease in patients with advanced head and neck neoplasms enrolled in two sequential Phase I dose escalation studies in which concomitant chemotherapy and radiotherapy were delivered on an alternate week schedule (i.e., 1 week of concomitant therapy alternated with 1 week of rest). METHODS AND MATERIALS: From 1986-1988, 65 patients were enrolled in two Phase I clinical trials. In trial one, 5-fluorouracil and hydroxyurea were administered concomitantly with radiation on an alternate week schedule (39 pts). In trial two, cisplatin was added to 5-fluorouracil and hydroxyurea (26 pts). Fifty-seven patients were evaluable for local control, including 26 patients who had failed prior local therapy and were retreated (group A), and 31 patients who had received no prior local therapy (group B). The median dose of RT and the median duration of therapy were 59.7 Gy and 12 weeks for group A, and 70.2 Gy and 14 weeks for group B, respectively. The biological effective dose of radiation therapy (RT) was calculated using the equation based on the linear quadratic model as proposed by J. Fowler. Univariate and multivariate logistic regression analyses were performed to evaluate prognostic factors for local control. RESULTS: Six of 26 patients in group A and 30 of 31 patients in group B had local control of disease. The 2-year Kaplan-Meier local failure rates were 84% for group A and 4% for group B, respectively. Despite the doubling of treatment duration compared to conventional daily radiotherapy and the low biological equivalent dose calculated (median biological equivalent dose for patients with local control of disease were 50.3 Gy and 48.8 Gy in groups A and B, respectively), local control was achieved in 5/17 patients in group A and 30/31 patients in group B who received RT dose of 59.4 Gy or higher. In multivariate logistic regression analysis, the only significant predictor for local control of disease was RT dose (p = 0.004). Treatment duration, chemotherapy dose intensities, age, and performance status were not significant variables. Decreasing the RT dose by 10 Gy would increase the rate of local failure by 24%. CONCLUSION: Our data suggest that prolongation of treatment duration to twice the normal duration of conventional once-a-day radiotherapy does not result in loss of local control when aggressive cell-cycle specific chemotherapy is given concomitantly with radiotherapy. The usual time-dose relationship based on RT alone does not appear to be applicable when concomitant chemotherapy is added. The clinical significance of biological equivalent dose calculation based on radiotherapy alone is unclear when chemotherapy is given with radiation.

Adult↗
PubMed2000

Salvage brachytherapy for patients with locally persistent nasopharyngeal carcinoma.

PURPOSE: Locally persistent nasopharyngeal carcinoma (NPC) carries an increased risk of local failure if additional treatment is not given. This study was conducted to evaluate the outcomes of patients with locally persistent NPC as treated by high-dose-rate (HDR) intracavitary brachytherapy, and to explore whether routine brachytherapy boost could improve the local control. METHODS AND MATERIALS: Eighty-seven patients with locally persistent NPC treated during 1990-1998 with HDR intracavitary brachytherapy were retrospectively analyzed. Fibreoptic nasopharyngoscopy was performed 3-6 weeks after completion of the primary external radiation therapy (ERT). Biopsies were only taken from suspicious areas. Those with complete regression of local disease were put on observation. Eighty-seven patients were shown to have persistent viable disease at a median time of 6 weeks post-RT. The distribution according to Ho's staging system at initial diagnosis was as follows: Stage I-8, II-33, III-41, IV-5; T1-19, T2-48, T3-20; N0-32, N1-22, N2-28, N3-5. CT scan for restaging was not performed after the documentation of persistent disease. Our policy was to treat all patients with persistent disease with brachytherapy irrespective of the extent of disease just prior to brachytherapy. They were treated with HDR intracavitary brachytherapy, with either cobalt sources or an iridium source, giving 22.5-24 Gy in 3 weekly sessions in all but 4 patients. This dose was prescribed at a distance of 1.5 cm from the center of the surface as defined by the sources in the first six patients and subsequently reduced to 1 cm for the others. Twelve patients were treated with neoadjuvant chemotherapy. To compare the efficacy of brachytherapy, another 383 consecutive nonmetastatic patients, treated with curative intent by ERT, during the years 1990-1993, were evaluated. Multivariate analysis was performed using the Cox regression proportional hazards model. RESULTS: The 5-year actuarial local failure-free survival (LFFS) rates and disease-specific survival rates for the brachytherapy group and ERT group were 85% and 76.6% (p = 0.15), and 72% and 67.8% (p = 0.2), respectively. The corresponding 5-year actuarial LFFS rates for T1, T2, and T3 disease were 94.7%, 88.2%, 67.4%, and 84.1%, 79.8%, 62.6%. In assessing the local control, only the T staging was significant on multivariate analysis (p = 0.0004). Other parameters such as age, sex, and persistence of disease (giving brachytherapy) were all nonsignificant. Complications were comparable between the two groups. In the persistent group, the local failure rates of the patients treated with and without neoadjuvant chemotherapy were 17% (2/12) and 13% (10/75) respectively. When analyzed according to different brachytherapy sources, the 5-year LFFS rates of the T1, T2, and T3 patients treated with iridium and cobalt sources were 100% vs. 85.7 (p = 0.19), 93.6% vs. 70% (p = 0.04), and 67.7% vs. 60% (p = 0.72). The difference was statistically significant for the T2 groups. When early T-stage (T1 and T2) patients were grouped together for analysis, the iridium group again showed a statistically significant improvement in 5-year LFFS rate when it was compared with the cobalt group (95.3% vs. 76.5%, p = 0.03) and the ERT alone group (95.3% vs. 81.5%, p = 0.03). The improvement of local control is attributed to a higher nasopharyngeal mucosal dose that is achieved by using small-size flexible applicators with an iridium source. It is interesting to note that the 5-year LFFS rates for the ERT alone group (T1: 84.1%, T2: 79.8%, T3: 62.6%) are comparable to the corresponding rates of the cobalt group. This information supports our speculation that an adequate booster treatment could compensate for inadequate primary treatment. The prognosis of patients with locally recurrent NPC is grave. Maximizing the local control is therefore crucial for the survival of the patients. (ABSTRACT TRUNCATED)

Analysis of Variance↗
PubMed2000

mRNA localization patterns in zebrafish oocytes.

In both invertebrate and vertebrate systems, the localization of maternal mRNAs is a common mechanism used to influence developmental processes, including the establishment of the dorsal/ventral axis, anterior/posterior axis, and the germ line (for review, see Bashirullah et al., 1998. Annu. Rev. Biochem. 67, 335-394). While the existence of localized maternal mRNAs has been reported in the zebrafish, Danio rerio, the precise localization patterns of these molecules during oogenesis has not been determined. In this study, in situ hybridization experiments were performed on zebrafish ovaries and activated eggs to examine different mRNA localization patterns. The results establish that while some maternal mRNAs remain ubiquitously distributed throughout the oocyte, other mRNAs follow specific localization patterns, including localization to the animal pole, localization to the vegetal pole, and cortical localization. The animal/vegetal axis is first apparent in stage II oocytes when the earliest mRNA localization is seen. Unique patterns of localization are seen in mature eggs as well. Some mRNAs maintain their oocyte localization patterns, while others localize upon egg activation (fertilization).

Animals↗
PubMed2003

Identification and characterization of the Xlsirt cis-acting RNA localization element.

There are many RNAs that are localized to the vegetal cortex of Xenopus laevis oocytes. One family of localized transcripts, Xlsirts (Xenopus laevis short interspersed repeat transcripts), are defined by the presence of non-coding repeat units 79-81 nucleotides long. Endogenous Xlsirt RNAs are localized through the METRO (message transport organizer) pathway that localizes RNAs during stages I and II of oogenesis. Interestingly, exogenous Xlsirt RNAs that are injected into oocytes can utilize both the METRO pathway as well as the Late pathway, which localizes RNAs during the late stages of oogenesis (stages III-VI). In all cases thus far analyzed, the localization process relies on the presence of cis-acting elements on the transcripts that are responsible for directing localization. To better understand the mechanism responsible for the use of the METRO and Late localization pathways, we sought to identify pathway-specific cis-acting localization elements contained in Xlsirts. The results showed that an intact 137 nucleotide element was necessary and sufficient to localize RNAs through the METRO and Late pathways. Further analysis of this element identified putative METRO and Late pathway localization sub-elements. Computer analysis relates the secondary structure of the 137 nt element to its ability to function as a localization element.

Amino Acid Sequence↗
PubMed2004

The relationship between regional and local species diversity in marine benthic communities: a global perspective.

The number of species coexisting in ecological communities must be a consequence of processes operating on both local and regional scales. Although a great deal of experimental work has been devoted to local causes of diversity, little is known about the effects of regional processes on local diversity and how they contribute to global diversity patterns in marine systems. We tested the effects of latitude and the richness of the regional species pool on the species richness of local epifaunal invertebrate communities by sampling the diversity of local sites in 12 independent biogeographic regions from 62 degrees S to 63 degrees N latitude. Both regional and local species richness displayed significant unimodal patterns with latitude, peaking at low latitudes and decreasing toward high latitudes. The latitudinal diversity gradient was represented at the scale of local sites because local species richness was positively and linearly related to regional species richness. The richness of the regional species pool explained 73-76% of local species richness. On a global scale, the extent of regional influence on local species richness was nonrandom-the proportion of regional biota represented in local epifaunal communities increased significantly from low to high latitudes. The strong effect of the regional species pool implies that patterns of local diversity in temperate, tropical, and high-latitude marine benthic communities are influenced by processes operating on larger spatiotemporal scales than previously thought.

Animals↗
PubMed2004

Analysis of HIV-1 viral infectivity factor-mediated proteasome-dependent depletion of APOBEC3G: correlating function and subcellular localization.

To study how HIV-1 viral infectivity factor (Vif) mediates proteasome-dependent depletion of host factor APOBEC3G, functional and nonfunctional Vif-APOBEC3G interactions were correlated with subcellular localization. APOBEC3G localized throughout the cytoplasm and co-localized with gamma-tubulin, 20 S proteasome subunit, and ubiquitin at punctate cytoplasmic bodies that can be used to monitor the Vif-APOBEC3G interaction in the cell. Through immunostaining and live imaging, we showed that a substantial fraction of Vif localized to the nucleus, and this localization was impaired by deletion of amino acids 12-23. When co-expressed, Vif exhibited more pronounced localization to the cytoplasm and reduced the total cellular levels of APOBEC3G but rarely co-localized with APOBEC3G at cytoplasmic bodies. On the contrary, Vif(C114S), which is inactive but continues to interact with APOBEC3G, stably associated with APOBEC3G in the cytoplasm, resulting in complete co-localization at cytoplasmic bodies and a dose-dependent exclusion of Vif(C114S) from the nucleus. Following proteasome inhibition, cytoplasmic APOBEC3G levels increased, and both proteins co-accumulated nonspecifically into a vimentin-encaged aggresome. Furthermore in the presence or absence of APOBEC3G, Vif localization was significantly altered by proteasome inhibition, suggesting that aberrant localization may also contribute to the loss of Vif function. Finally mutations at Vif Ile(9) disrupted the ability of Vif or Vif(C114S) to coimmunoprecipitate and to co-localize with APOBEC3G, suggesting that the N terminus of Vif mediates interactions with APOBEC3G. Taken together, these results demonstrate that cytoplasmic Vif-APOBEC3G interactions are required but are not sufficient for Vif to modulate APOBEC3G and can be monitored by co-localization in vivo.

APOBEC-3G Deaminase↗
PubMedDate not supplied

Thermoradiotherapy for locally recurrent breast cancer with skin involvement.

PURPOSE: This retrospective analysis investigated the effectiveness and side-effects of combined hyperthermia and radiation therapy in locally recurrent breast cancer after primary modified radical mastectomy. The aim of the thermoradiotherapy was to reduce the substantial risk of symptomatic chest wall disease. MATERIALS AND METHODS: Between May 1995-August 1998, 39 extensively pre-treated women with progressive locoregional chest wall tumours were treated with local radiofrequency hyperthermia, given twice a week immediately before radiotherapy. Sixty-two per cent of the patients had received previous radiotherapy, with a median dose of 50 Gy, 64% had received chemotherapy, 36% hormonal therapy, and 13% local therapy with miltefosin, respectively. Nine patients were treated for microscopic residual disease after local tumour excision (R1-resection) and 30 patients for gross macroscopic nodular recurrences. Twenty-seven patients had two adjacent hyperthermia fields at the ipsilateral chest wall to cover the whole irradiation area. Each field received a median of seven local hyperthermia sessions (range 2-12, average 5.6 sessions) just before radiation therapy, with a median dose of 60 Gy (range 30-68 Gy). The monitored maximum(average) and average(average) epicutaneous temperatures were 42.1 degrees C and 41.0 degrees C, respectively. Maximum(average) and average(average) intratumoural temperatures of 43.0 degrees C and 41.1 degrees C, respectively, were achieved in nine chest wall recurrences with intratumoural temperature probes. Concurrent hormonal therapy was administered in 48%, and concurrent chemotherapy in 10% of patients. RESULTS: Median overall survival time was 28 months (Kaplan Meier), with 71% and 54% of patients living 1 and 2 years after thermoradiotherapy. The median time to local failure has not been reached, local tumour control after 2 years being 53%. Actuarial 1 and 2 year local tumour controls for microscopic residual disease were 89%, and for macroscopic nodular recurrences 71% and 46%, respectively (p = 0.09). Actuarial 1 and 2 year local tumour controls after treatment with a total dose of less than 60 Gy were 51% and 38%, respectively, and, after a total dose greater than 60 Gy, 84% and 60% (p = 0.01), respectively. Actuarial 1 year local tumour control was 92% after complete tumour remission, versus 57% after partial remission (p = 0.002). Three of the 39 patients died of cancer en cuirasse, 13 patients due to distant metastases. Acute thermoradiotherapy related erythema, dry desquamation and moist desquamation were seen in 28.2%, 30.7%, and 30.7% of patients, respectively. Soft tissue necrosis occurred in two patients with previous post-operative delayed wound healing, and in one patient above a silicon implant. CONCLUSION: This study showed that, in extensively pre-treated patients with locally recurrent breast cancer, local tumour control after thermoradiotherapy depended on tumour resectability, response of macroscopic tumour to thermoradiotherapy, and total irradiation dose.

Adult↗
PubMed1997

A small conserved domain in the yeast Spa2p is necessary and sufficient for its polarized localization.

SPA2 encodes a yeast protein that is one of the first proteins to localize to sites of polarized growth, such as the shmoo tip and the incipient bud. The dynamics and requirements for Spa2p localization in living cells are examined using Spa2p green fluorescent protein fusions. Spa2p localizes to one edge of unbudded cells and subsequently is observable in the bud tip. Finally, during cytokinesis Spa2p is present as a ring at the mother-daughter bud neck. The bud emergence mutants bem1 and bem2 and mutants defective in the septins do not affect Spa2p localization to the bud tip. Strikingly, a small domain of Spa2p comprised of 150 amino acids is necessary and sufficient for localization to sites of polarized growth. This localization domain and the amino terminus of Spa2p are essential for its function in mating. Searching the yeast genome database revealed a previously uncharacterized protein which we name, Sph1p (a2p omolog), with significant homology to the localization domain and amino terminus of Spa2p. This protein also localizes to sites of polarized growth in budding and mating cells. SPH1, which is similar to SPA2, is required for bipolar budding and plays a role in shmoo formation. Overexpression of either Spa2p or Sph1p can block the localization of either protein fused to green fluorescent protein, suggesting that both Spa2p and Sph1p bind to and are localized by the same component. The identification of a 150-amino acid domain necessary and sufficient for localization of Spa2p to sites of polarized growth and the existence of this domain in another yeast protein Sph1p suggest that the early localization of these proteins may be mediated by a receptor that recognizes this small domain.

Amino Acid Sequence↗
PubMed2000

EEG dipole source localization using artificial neural networks.

Localization of focal electrical activity in the brain using dipole source analysis of the electroencephalogram (EEG), is usually performed by iteratively determining the location and orientation of the dipole source, until optimal correspondence is reached between the dipole source and the measured potential distribution on the head. In this paper, we investigate the use of feed-forward layered artificial neural networks (ANNs) to replace the iterative localization procedure, in order to decrease the calculation time. The localization accuracy of the ANN approach is studied within spherical and realistic head models. Additionally, we investigate the robustness of both the iterative and the ANN approach by observing the influence on the localization error of both noise in the scalp potentials and scalp electrode mislocalizations. Finally, after choosing the ANN structure and size that provides a good trade off between low localization errors and short computation times, we compare the calculation times involved with both the iterative and ANN methods. An average localization error of about 3.5 mm is obtained for both spherical and realistic head models. Moreover, the ANN localization approach appears to be robust to noise and electrode mislocations. In comparison with the iterative localization, the ANN provides a major speed-up of dipole source localization. We conclude that an artificial neural network is a very suitable alternative for iterative dipole source localization in applications where large numbers of dipole localizations have to be performed, provided that an increase of the localization errors by a few millimetres is acceptable.

Brain↗
PubMed2003

Health promotion activities in annual reports of local governments: 'Health for All' targets as a tool for content analysis.

BACKGROUND: This article presents an instrument to study the annual reporting of health promotion activities in local governments within the three intervention municipalities of the Stockholm Diabetes Prevention Program (SDPP). The content of health promotion activities are described and the strengths, weaknesses and relevance of the method to health promotion discussed. METHOD: A content analysis of local governmental reports from 1995-2000 in three Swedish municipalities. A matrix with WHO's 38 'Health for All' (HFA) targets from 1991 was used when coding the local health promotion activities. RESULTS: There are many public health initiatives within the local governmental structure even if they are not always addressed as health promotion. The main focuses in the local governmental reports were environmental issues, unemployment, social care and welfare. CONCLUSIONS: Local governmental reports were found to be a useful source of information that could provide knowledge about the priorities and organizational capacities for health promotion within local authorities. Additionally the HFA targets were an effective tool to identify and categorize systematically local health promotion activities in the annual reports of local governments. Identifying local health promotion initiatives by local authorities may ease the development of a health perspective and joint actions within the existing political and administrative structure. This paper provides a complementary method of attaining and structuring information about the local community for developments in health promotion.

Government Agencies↗
PubMed1999

Long-term follow-up of patients with rectal cancer managed by local excision with and without adjuvant irradiation.

OBJECTIVE: The long-term outcomes of patients undergoing local excision with or without pelvic irradiation were examined to define the role of adjuvant irradiation after local excision of T1 and T2 rectal cancers. METHODS: Ninety-nine patients with T1 or T2 rectal cancers underwent local excision with or without adjuvant irradiation at Massachusetts General Hospital and Emory University Hospital between January 1966 and January 1997. Of these, 52 patients were treated by local excision alone and 47 patients by local excision plus adjuvant irradiation. Twenty-six of these 47 patients were treated by irradiation in combination with 5-fluorouracil chemotherapy. The outcomes of these groups were compared. RESULTS: The 5-year actuarial local control and recurrence-free survival rates were 72% and 66%, respectively, for the local excision alone group and 90% and 74%, respectively, for the adjuvant irradiation group. This improvement in outcome was evident despite the presence of a higher-risk patient population in the adjuvant irradiation group. Adverse pathologic features such as poorly differentiated histology and lymphatic or blood vessel invasion decreased local control and recurrence-free survival rates in the local excision only group. Adjuvant irradiation significantly improved 5-year outcomes in patients with high-risk pathologic features. Four cases of late local recurrence were seen at 64, 72, 86, and 91 months in the adjuvant irradiation group. CONCLUSIONS: The authors recommend adjuvant chemoradiation for all patients undergoing local excision for T2 tumors, and for T1 tumors with high-risk pathologic features. The four cases of late local failures beyond 5 years in the adjuvant irradiation group underscores the need for careful long-term follow-up in these patients.

Actuarial Analysis↗
PubMed2005

Effective representation using ICA for face recognition robust to local distortion and partial occlusion.

The performance of face recognition methods using subspace projection is directly related to the characteristics of their basis images, especially in the cases of local distortion or partial occlusion. In order for a subspace projection method to be robust to local distortion and partial occlusion, the basis images generated by the method should exhibit a part-based local representation. We propose an effective part-based local representation method named locally salient ICA (LS-ICA) method for face recognition that is robust to local distortion and partial occlusion. The LS-ICA method only employs locally salient information from important facial parts in order to maximize the benefit of applying the idea of "recognition by parts." It creates part-based local basis images by imposing additional localization constraint in the process of computing ICA architecture I basis images. We have contrasted the LS-ICA method with other part-based representations such as LNMF (Localized Nonnegative Matrix Factorization) and LFA (Local Feature Analysis). Experimental results show that the LS-ICA method performs better than PCA, ICA architecture I, ICA architecture II, LFA, and LNMF methods, especially in the cases of partial occlusions and local distortions.

Algorithms↗
PubMed2006

A truce with neutral theory: local deterministic factors, species traits and dispersal limitation together determine patterns of diversity in stream invertebrates.

1. Studies seeking to explain local patterns of diversity have typically relied on niche explanations, reflected in correlations with local environmental conditions, or neutral theory, invoking dispersal processes and speciation. 2. We used macroinvertebrate community data from 10 streams that varied independently in local ecological conditions and spatial proximity. Neutral theory predicts that similarity in communities will be negatively associated with distance between sites, while niche theory suggests that community similarity will be positively associated with similarity in local ecological conditions. 3. Similarity in total invertebrate, grazer and predator assemblages showed negative relationships with distance and, for grazers and predators, positive relationships with local ecological conditions. However, the best model predicting community similarity in all three cases included aspects of both local ecological conditions and distance between sites. 4. When assemblages were analysed according to dispersal ability, high-dispersal species were shown to be freely accessing all sites and community similarity was not well predicted by either local ecology or spatial separation. Assemblages of species with low and moderate dispersal ability were best predicted by combined models, including distance between sites and local ecological factors. 5. The results suggest that the perceived dichotomy between neutral and local environmental processes in determining local patterns of diversity may not be useful. Neutral and niche processes structured these communities differentially depending on trophic level and species traits. 6. We emphasize the potential for both dispersal processes and local environmental conditions to explain local patterns of diversity.

Animals↗
PubMedDate not supplied

Micro-light guide spectrophotometric measurement of changes in local haemoglobin oxygenation and concentration in the rabbit lung induced by hypoxia and hyperoxia.

Due to the high flexibility of the micro-light guides used with the Erlangen micro-light guide spectrophotometer (EMPHO) the instrument can be coupled to the lung surface without interfering with the local lung mechanics. The local pressure exerted on the lung varies between 45 and 47 mg/cm2. This enables the continuous investigation of local haemoglobin oxygenation and relative local haemoglobin concentration. The effect of different inspired oxygen concentrations on local oxygen saturation of intravascular haemoglobin and relative local haemoglobin concentration was investigated in 6 rabbits. The animals were anaesthetized, intubated and artificially ventilated. After thoracotomy, a light guide was placed on the pleural lung surface and haemoglobin spectra were measured at a frequency of 5 Hz using the EMPHO. Two types of changes in the local haemoglobin concentration were observed; one was correlated with the respiratory cycle. During inspiration a decrease in relative local haemoglobin concentration was observed. Opposite changes occurred during expiration. These changes were observed with simultaneous changes in local haemoglobin oxygenation. The oxygenation increased during inspiration and decreased during expiration. The amplitude of the oxygenation changes depended on the fraction of inspired oxygen FiO2. A second type of reaction in local haemoglobin concentration was observed when the inspired oxygen concentration was decreased or increased by changing the FiO2. A decrease in the oxygen partial pressure in the inspired gas mixture (PiO2) was associated with an increase in relative local haemoglobin concentration, whereas an increase in PiO2 was accompanied by a decrease in relative local haemoglobin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Neutrophil accumulation in ischemic canine myocardium. Insights into time course, distribution, and mechanism of localization during early reperfusion.

BACKGROUND: We have previously demonstrated that chemotactic factors released from the ischemic canine myocardium peak early during reperfusion and that they elicit neutrophil adherence reactions in vitro that are dependent on the CD18 glycoprotein family. In this study we investigated the hypothesis that neutrophil localization in ischemic canine myocardium in vivo occurs over a similar time course during early reperfusion and involves a CD18-dependent mechanism. METHODS AND RESULTS: We occluded the circumflex coronary artery for 1 hour in acute, open-chest dogs, followed by reperfusion for 1, 2, 3, or 4 hours. Regional myocardial blood flow was determined using radiolabeled microspheres, and localization was traced using technetium-99m-labeled autologous neutrophils. In the first hour of reperfusion, neutrophil localization occurred preferentially within the subendocardial region and was inversely related to flow. Neutrophil localization diminished across the ischemic myocardium from endocardium to epicardium but remained negatively related to flow in the midmyocardial region. Regardless of flow, little neutrophil localization occurred in the subepicardial region. Neutrophil localization was greatest in the first hour of reperfusion and diminished thereafter. By 4 hours of reperfusion, the rate of localization was markedly attenuated relative to 1 hour. Dogs given anti-CD18 monoclonal antibody R15.7 (1 mg/kg i.v.) before occlusion underwent 1 hour of occlusion followed by 1 hour of reperfusion. When compared with 1-hour reperfusion controls, the R15.7-treated dogs demonstrated significant attenuation of neutrophil localization in the subendocardial region. CONCLUSIONS: These data support the concepts that rapid neutrophil localization during reperfusion occurs within regions of previous myocardial ischemia and that neutrophils preferentially localize within the subendocardial region. The rate of neutrophil localization is greatest within the first hour after the initiation of reperfusion, and localization is, at least in part, CD18 dependent. Therapies directed against neutrophil-mediated reperfusion injury should be initiated with these considerations in mind.

Animals↗
PubMed1998

Neural mechanisms of global and local processing. A combined PET and ERP study.

The neural mechanisms of hierarchical stimulus processing were investigated using a combined event-related potentials (ERPs) and positron emission tomography (PET) approach. Healthy subjects were tested under two conditions that involved selective or divided attention between local and global levels of hierarchical letter stimuli in order to determine whether and where hemispheric differences might exist in the processing of local versus global information. When attention was divided between global and local levels, the N2 component of the ERPs (260- to 360-msec latency) elicited by the target stimuli showed asymmetries in amplitude over the two hemispheres. The N2 to local targets was larger over the left hemisphere, but the N2 to global targets tended to be slightly larger over the right hemisphere. However, the shorter-latency, sensory-evoked P1 component (90- to 150-msec latency) was not different for global versus local targets under conditions of divided attention. In contrast, during selective attention to either global or local targets, asymmetries in the N2 component were not observed. But under selective attention conditions, the sensory-evoked P1 components in the extrastriate cortex were enlarged for global versus local attention. Increased regional cerebral blood flow in the posterior fusiform gyrus bilaterally was observed in the PET data during selective attention to either global or local targets, but neither these nor the P1 component showed any tendency toward hemispheric difference for global versus local attention. Neither were there any activations observed in the parietal lobe during selective attention to global versus local targets. Together these data indicate that early sensory inputs are not modulated to gate global versus local information differentially into the two hemispheres. Rather, later stages of processing that may be asymmetrically organized in the left and right hemispheres operate in parallel to process global and local aspects of complex stimuli (i.e., the N2 effect of the ERPs). This pattern of results supports models proposing that spatial frequency analysis is only asymmetric at higher stages of perceptual processing and not at the earliest stages of visual cortical analysis.

Adult↗
PubMed2004

A comparison of random draw and locally neutral models for the avifauna of an English woodland.

BACKGROUND: Explanations for patterns observed in the structure of local assemblages are frequently sought with reference to interactions between species, and between species and their local environment. However, analyses of null models, where non-interactive local communities are assembled from regional species pools, have demonstrated that much of the structure of local assemblages remains in simulated assemblages where local interactions have been excluded. Here we compare the ability of two null models to reproduce the breeding bird community of Eastern Wood, a 16-hectare woodland in England, UK. A random draw model, in which there is complete annual replacement of the community by immigrants from the regional pool, is compared to a locally neutral community model, in which there are two additional parameters describing the proportion of the community replaced annually (per capita death rate) and the proportion of individuals recruited locally rather than as immigrants from the regional pool. RESULTS: Both the random draw and locally neutral model are capable of reproducing with significant accuracy several features of the observed structure of the annual Eastern Wood breeding bird community, including species relative abundances, species richness and species composition. The two additional parameters present in the neutral model result in a qualitatively more realistic representation of the Eastern Wood breeding bird community, particularly of its dynamics through time. The fact that these parameters can be varied, allows for a close quantitative fit between model and observed communities to be achieved, particularly with respect to annual species richness and species accumulation through time. CONCLUSION: The presence of additional free parameters does not detract from the qualitative improvement in the model and the neutral model remains a model of local community structure that is null with respect to species differences at the local scale. The ability of this locally neutral model to describe a larger number of woodland bird communities with either little variation in its parameters or with variation explained by features local to the woods themselves (such as the area and isolation of a wood) will be a key subsequent test of its relevance.

Animals↗