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[Local recurrence of differentiated thyroid carcinoma effectively treated by local injection of OK-432].

Local recurrence of differentiated thyroid carcinoma in a 67-year-old woman was treated by topical injection of OK-432 every 2-4 weeks. Recurrent tumors turned into small scar-like tissues after 9 months of OK-432 administration. The bleeding from the tumor was well controlled. Secondary recurrent tumors were also effectively treated in the same manner. About 2 years have passed since the start of the treatment and the local recurrence is well controlled. We conclude that topical injection of OK-432 might be a good modality of treatment for the local recurrence of thyroid carcinoma.

Carcinoma↗

Localized complications from local anesthesia.

The inherent safety of local anesthetics allows practitioners to use them frequently with the confidence that adverse events are rare. Nevertheless, complications can occur. The aim of this article is to briefly review the localized adverse events that may result from local anesthetic administration. Descriptions of each complication will be followed by suggestions for prevention and management. In spite of a dentist's conscientious practice, many of these complications cannot always be prevented.

Anesthesia, Dental↗

Local and systemic delivery of low molecular weight heparin following PTCA: acute results and 6-month follow-up of the initial clinical experience with the porous balloon (PILOT-study). Preliminary Investigation of Local Therapy Using Porous PTCA Balloons.

The purpose of this study was to assess safety and feasibility of intracoronary delivery of reviparin using a porous balloon following percutaneous transluminal coronary angioplasty. The 2.7 mm porous balloon used in this study had 35 holes arranged in a spiral pattern. Eighteen patients (male n = 10, female n = 8, age 63 +/- 9 years) undergoing successful PTCA in coronary arteries with a vessel diameter of 2.5 to 3.0 mm determined by online QCA (LAD = 11, RCX = 3, RCA = 4) were included. They received a bolus of 7,000 anti-Xa-IU reviparin followed by local delivery of 1,500 anti-Xa-IU in 4 ml with an injection pressure of 2 atm. The patients received additionally 10500 anti-Xa-units intravenously during the following 24 hours and a daily dose of 7000 anti-Xa-units reviparin subcutaneously for the following 28 days. Angiograms were obtained before and after PTCA, directly after local delivery, at 24 hours postintervention and after 6 months. The primary success rate was 100%. Quantitative coronary angiography showed a minimum luminal diameter of 0.42 +/- 0.14 mm before PTCA, 1.87 +/- 0.45 after PTCA, 1.67 +/- 0.43 after LDD, 1.63 +/- 0.46 after 24 hours, and 1.06 +/- 0.6 after 6 months. Angiographic follow-up was obtained in all patients. No major complications occurred during the 6-month follow-up period. The angiographic restenosis rate was 28% (5/18) at follow-up. This study demonstrates safety and feasibility of local intracoronary delivery of reviparin with a porous balloon following PTCA even in smaller diameter coronary arteries.

Aged↗

Local intramural heparin delivery during primary angioplasty for acute myocardial infarction: results of the Local PAMI Pilot Study.

The feasibility and safety of local heparin delivery during acute infarct angioplasty was evaluated in a prospective, multicenter, 120-patient series. Angioplasty was performed using standard techniques, after which heparin (4,000 U) was delivered locally; 25% of patients received stents. Procedural success was reported in 98% of patients; 6.7% of patients suffered death, reinfarction, recurrent ischemia, or stroke during the index hospitalization. The 6-month target vessel revascularization rate was 12.5%. Local heparin therapy with provisional stenting in acute myocardial infarction patients is safe, feasible, associated with a low rate of infarct artery revascularization at 6 months, and may potentially eliminate the need for systemic heparin following the procedure.

Aged↗

Nuclear shape analysis for the assessment of local invasion and metastases in clinically localized prostate carcinoma.

BACKGROUND: Nuclear shape analysis of histologic sections from radical prostatectomy specimens has retrospectively predicted outcome in patients with clinically localized prostate carcinoma. If outcome could be predicted preoperatively by nuclear shape analysis, patients might be selected better for definitive surgical therapy. Morphometric analysis of preoperative biopsies, however, has not correlated positively with values obtained from analysis of prostatectomy specimens. METHODS: The nuclear shapes of histologic specimens of 20 organ-confined carcinomas, 10 periprostatic fat-invasive carcinomas, 10 seminal vesicle-invasive carcinomas, and 12 lymph node-metastatic carcinomas from 52 patients who had undergone radical prostatectomy for clinically localized disease were evaluated. RESULTS: Nuclei from areas of extraprostatic invasion or regional lymph node metastases were less round than those from the corresponding intraprostatic portion of the tumor (nuclear roundness factor (mean +/- SD) PPF, 51.2 +/- 3.1 vs. 31.2 +/- 3.2; SV, 52.4 +/- 4.1 vs. 31.6 +/- 2.5; and LN, 57.3 +/- 3.1 vs. 36.4 +/- 1.8; paired Student's t tests, P < 0.001). Cells sampled from the periphery of organ-confined tumors had a greater nuclear roundness factor (49.1 +/- 1.5) than did those sampled from the center (34.5 +/- 2.0; P < 0.001) or randomly throughout the tumor (37.8 +/- 1.6; P < 0.001). Nuclear roundness factors for all extraprostatic tumor foci and for peripheral tumor cells in organ-confined disease were similar (analysis of variance, P > 0.05). The intraprostatic portions of randomly sampled primary tumors had similar nuclear roundness factors, regardless of pathologic stage (P > 0.05). Among organ-confined carcinomas, nuclear shape was unrelated to tumor volume. CONCLUSIONS: Pathologic stage in clinically localized prostate carcinoma cannot be determined by the nuclear shape profiles of intraprostatic tumor cells. Thus, patients with a poor prognosis or high pathologic stage can be recognized only when samples for morphometric analysis include high proportions of nuclei from the extra-prostatic carcinoma and nuclei from the periphery of organ-confined carcinoma that may not be sampled routinely by prostate biopsy.

Adipose Tissue↗

Localization of swallow-Green Fluorescent Protein in Drosophila oogenesis and implications for the role of swallow in RNA localization.

The localization of a hybrid protein composed of swallow and Green Fluorescent Protein (GFP) during Drosophila oogenesis is reported. I constructed a hybrid gene with GFP inserted into an internal position of swallow. This gene was integrated into the Drosophila genome and provides full swallow+ function, as assayed by the complete rescue of strong swallow mutants. Swallow-GFP is localized at all points along the oocyte cortex from vitellogenic stages of oogenesis through the end of oogenesis. Higher concentrations of swallow-GFP are present at the anterior oocyte cortex than at the lateral and posterior oocyte cortices at Stages 10 and 11, when bicoid and htsN4 mRNA transport from nurse cells and localization in the oocyte are most active. At Stage 9 and at Stages 12-14 swallow-GFP is equally distributed at the anterior, lateral, and posterior oocyte cortices. The position of swallow-GFP in vitellogenic stages is identical to the position of endogenous swallow protein determined by indirect immunofluorescence using an anti-swallow antibody. At the oocyte cortex, swallow-GFP is present in particulate structures that lie within or just internal to the dense cortical actin meshwork. These particles show little or no movement, suggesting that they are attached to or embedded in the oocyte cortex. These observations are most easily interpreted in the context of mRNA anchoring or microtubule organizing functions for the swallow protein.

Animals↗

Local delivery of magnetic resonance (MR) contrast agent in kidney using thermosensitive liposomes and MR imaging-guided local hyperthermia: a feasibility study in vivo.

PURPOSE: To investigate the feasibility of local delivery of a magnetic resonance (MR) contrast agent in vivo using paramagnetic thermosensitive liposomes and infrared (IR) laser-induced local hyperthermia under real-time MR thermometry on rabbit kidney. MATERIALS AND METHODS: Respiratory gated, radio frequency (RF)-spoiled gradient-echo sequences were used for precise MR temperature mapping (SD = 1 degrees C). In vivo heating experiments confirmed local release of MR contrast agent from liposomes. RESULTS: T1 decreased from 800 msec to about 500 msec, as measured after tissue cooling, in those locations where the renal parenchyma was heated above the phase transition temperature of the liposome membrane. CONCLUSION: The release of MR contrast agent has been demonstrated in rabbit kidney in vivo. This may be used as a reporter for simultaneous release of therapeutic agents.

Animals↗

Localized nodular myositis and the diagnosis of the localized muscle mass.

Localized nodular myositis (LNM) is a rare variant of polymyositis beginning with inflammatory nodules within muscles. Only seven cases have so far been reported in the literature. We describe a probable further case of LNM in a 67-year-old man with ischemic claudication of the left leg for three years who presented with painful nodules in the left gastrocnemius muscle and signs of systemic disease; a complete follow-up was not possible, because the patient died after only two months and autopsy was not performed. Muscle biopsy showed localized areas of necrotic and inflammatory pleomorphic changes, in keeping with the features of the other known cases. The ultrastructural findings (not previously reported in this disease) were characterized by marked changes of endomysial capillaries, with fibroblastic metamorphosis of the endothelial cells, and by the presence of filamentous inclusions in the myonuclei. The differential diagnosis of LNM from other localized muscle masses, chiefly from muscle infarct, is discussed.

Aged↗

Antibacterial immunity of lower airways: local or localized?

Clearance of bacteria in the bronchoalveolar lavage, the level and functional activity of IgA and changes in the cellular composition of BAL were examined in mice after supralaryngeal immunization and subsequent challenge with Klebsiella pneumoniae. More than 60% of the bacterial inoculum was removed by nonspecific mechanisms within 90 min after inoculation; within the time interval 1.5-3.5 h, clearance was significantly accelerated in locally immunized mice. The enhancement of clearance effectiveness is specific and increases proportionally with the length of immunization (1 less than 2 less than 4 weeks); it is of short duration and towards the end of the 3rd week after immunization, in 73% of immunized animals, the clearance values did not differ from values found in controls. The local immunization did not influence the total level of IgA in BAL, the formation of specific IgA antibody was minimal, in vivo binding of IgA to klebsiella could not be demonstrated. In immunized mice, a significant increase in the numbers of PMN and lymphocytes, as well as an increased activity of phagocytic cell (PMN, MP) was found in BAL. The time interval of 1.5-3.5 h after challenge bounds the space for mechanisms, activated by local immunization in lower airways. The actual participation of individual factors in the accelerated elimination of bacteria from the lumen of airways, remains unclear so far.

Animals↗

Prostate cancer: comparison of local staging accuracy of pelvic phased-array coil alone versus integrated endorectal-pelvic phased-array coils. Local staging accuracy of prostate cancer using endorectal coil MR imaging.

To compare the visibility of anatomical details and prostate cancer local staging performance of pelvic phased-array coil and integrated endorectal-pelvic phased-array coil MR imaging, with histologic analysis serving as the reference standard. MR imaging was performed in 81 consecutive patients with biopsy-proved prostate cancer, prior to radical prostatectomy, on a 1.5T scanner. T2-weighted fast spin echo images of the prostate were obtained using phased-array coil and endorectal-pelvic phased-array coils. Prospectively, one radiologist, retrospectively, two radiologists and two less experienced radiologists working in consensus, evaluated and scored all endorectal-pelvic phased-array imaging, with regard to visibility of anatomical details and local staging. Receiver operator characteristics (ROC) analysis was performed. Anatomical details of the overall prostate were significantly better evaluated using the endorectal-pelvic phased-array coil setup (P<0.05). The overall local staging accuracy, sensitivity and specificity for the pelvic phased-array coil was 59% (48/81), 56% (20/36) and 62% (28/45), and for the endorectal-pelvic phased-array coils 83% (67/81), 64% (23/36) and 98% (44/45) respectively, for the prospective reader. Accuracy and specificity were significantly better with endorectal-pelvic phased-array coils (P<0.05). The overall staging accuracy, sensitivity and specificity for the retrospective readers were 78-79% (P<0.05), 56-58% and 96%, for the endorectal-pelvic phased-array coils. Area under the ROC curve (Az) was significantly higher for endorectal-pelvic phased-array coils (Az=0.74) compared to pelvic phased-array coil (Az=0.57), for the prospective reader. The use of endorectal-pelvic phased array coils resulted in significant improvement of anatomic details, extracapsular extension accuracy and specificity. Overstaging is reduced significantly with equal sensitivity when an endorectal-pelvic phased-array coil is used.

Adult↗

Phase transitions in the neuropercolation model of neural populations with mixed local and non-local interactions.

We model the dynamical behavior of the neuropil, the densely interconnected neural tissue in the cortex, using neuropercolation approach. Neuropercolation generalizes phase transitions modeled by percolation theory of random graphs, motivated by properties of neurons and neural populations. The generalization includes (1) a noisy component in the percolation rule, (2) a novel depression function in addition to the usual arousal function, (3) non-local interactions among nodes arranged on a multi-dimensional lattice. This paper investigates the role of non-local (axonal) connections in generating and modulating phase transitions of collective activity in the neuropil. We derived a relationship between critical values of the noise level and non-locality parameter to control the onset of phase transitions. Finally, we propose a potential interpretation of ontogenetic development of the neuropil maintaining a dynamical state at the edge of criticality.

Algorithms↗

Covariance of preference and performance on normal and novel hosts in a locally monophagous and locally polyphagous butterfly population.

Covariance between preference and performance was quantified for Papilio glaucus strains derived from a locally monophagous Florida population and a locally polyphagous Ohio population. I used two-choice assays to assess relative host preferences of mothers for plant species that represent reciprocal normal and novel hosts for each population (i.e., Liriodendron tulipifera and Magnolia virginiana) and a split-brood design to quantify relative performance of their progeny on each host. Covariance between preference and proxies of performance was detected independently within each population, which is a level of genetic structure at which such covariance has rarely been documented. These results support the hypothesis that preference-performance covariance can exist in populations that have no obvious internal host-associated structure. In the Ohio strain, all proxies of performance (larval duration, pupal mass, relative growth rate, and survival) were significantly correlated with relative preference for the normal host, L. tulipifera. In the Florida strain, however, only pupal mass was correlated with maternal preference, and this correlation was not in the direction expected. Progeny that attained the heaviest mass were derived from mothers that preferred L. tulipifera, the locally rare host. The nature of the preference-performance links was not in the manner predicted by conventional optimal oviposition theory, whereby host-associated tradeoffs have been considered an implicit element. Relative performance was congruent across hosts, regardless of whether mothers preferred L. tulipifera, M. virginiana, or neither host. After considering possible genetic and nongenetic explanations that could account for preference-performance covariance in P. glaucus, I conclude that this covariance has a genetic basis. Likely, multiple genetic control mechanisms (e.g., pleiotropy and co-adaptation) integrate at the level of different trait combinations and/or a particular trait combination to generate observed patterns.

Adaptation, Physiological↗

Localized and locally advanced bladder cancer.

Localized and locally advanced bladder cancer represents a heterogeneous spectrum of diseases with different biologic and clinical behavior. It varies with respect to invasive potential, propensity for metastases, and sensitivity to chemotherapy. Although several significant surgical advances have been made over the past 20 years in the treatment of muscle-invasive bladder cancer, resulting in decreases in perioperative morbidity and mortality and improvement of quality of life in patients with continent urinary diversions, the natural history of the disease has remained unaltered. Advances in chemotherapy for metastatic disease have prompted trials of systemic therapy in patients with early stage, high-risk disease administered before or after local therapy consisting of cystectomy or radiotherapy. The data available from nonrandomized and randomized trials have not definitively established the exact role of neoadjuvant chemotherapy and its impact on survival. Even if neoadjuvant chemotherapy does not improve survival, preliminary data suggest that bladder preservation may be possible in selected patients and that such combined therapy will hopefully lead to better patient management. The trials of postoperative chemotherapy provide insufficient evidence to support the routine use of adjuvant chemotherapy in clinical practice as a result of small sample size, confusing analyses, and the reporting of questionable conclusions. New large-scale, multicenter trials are imperative to provide convincing results. A better understanding of the microbiology of bladder cancer will influence the search for new therapeutic modalities. Molecular-targeted small-molecule therapy and monoclonal antibodies have begun to dominate contemporary studies.

Chemotherapy, Adjuvant↗

Alpha-, beta II- and gamma-subspecies of protein kinase C localized in the monkey hippocampus: pre- and post-synaptic localization of gamma-subspecies.

Protein kinase C (PKC) has attracted wide attention as a key enzyme for the expression of long-term potentiation in the hippocampus, a basic model for memory. It is of interest to study the detailed localization of PKC subspecies in the monkey hippocampus. We used immunocytochemistry to examine the localization of PKC subspecies in the hippocampus of the monkey, Macaca mulatta. Subspecies of PKC in the monkey could be separated by hydroxyapatite chromatography and the elution profile proved to be similar to that of the rat. Antibodies against each alpha, beta II and gamma-subspecies of the rat specifically reacted with the respective subspecies of monkey PKC. The alpha-, beta II- and gamma-subspecies were distinctly distributed in the hippocampus. The beta I-subspecies was not evident in the hippocampus. While both the alpha- and gamma-subspecies immunoreactive pyramidal cells were distributed throughout the hippocampus (CA1-CA3), the beta II-subspecies immunoreactive cells were scattered only in the CA1 region. The gamma-subspecies was found in granule cells and dendrites in the dentate gyrus, in mossy fibers and in their terminals in the CA3 region. The alpha-subspecies was also present in granule cells and in the dendrites but not in the mossy fibers. Glial cells did not stain with any of the antibodies used. Electron microscopy clearly showed that the gamma-subspecies was localized in both presynaptic terminals and post-synaptic dendrites. These observations suggest that subspecies of PKC in the monkey hippocampus may be involved in distinct functions and that the gamma-subspecies of PKC may act pre- and post-synaptically in pyramidal cells of the hippocampus.

Amino Acid Sequence↗

Ultrastructural localization of mu-opioid receptors in the superficial layers of the rat cervical spinal cord: extrasynaptic localization and proximity to Leu5-enkephalin.

Many of the analgesic effects of opiate drugs and of endogenous opioid ligands, such as Leu5-enkephalin (LE) are thought to be mediated in part by mu-opioid receptors (MOR) in the dorsal horn of the spinal cord. To establish the cellular sites for the spinally mediated analgesic effects of MOR activation and the potential anatomical substrates for interactions with LE, we examined the ultrastructural localization of MOR and LE immunoreactivities in the adult rat cervical spinal cord (C3-C5). Anti-MOR sera recognizing the carboxyl terminal domain of MOR was localized using immunoperoxidase and immunogold-silver methods. mu-opioid receptor-like immunoreactivity (MOR-LI) was observed mainly in the superficial layers of the dorsal horn. Electron microscopy of this region revealed that small unmyelinated axons and axon terminals constituted 48% (91/189) and 15% (28/189), respectively, while dendrites comprised 36% (68/189) of the total population of neuronal profiles containing the MOR. MOR-LI was localized mainly along extrasynaptic portions of the plasma membrane in both axons and dendrites. In sections dually labeled for MOR and LE, 21% (14/68) of the dendrites containing MOR-LI closely apposed or received synaptic contact from axon terminals exhibiting LE reaction product. The results provide the first ultrastructural evidence that within the dorsal horn of the spinal cord, LE, as well as exogenous opiates may alter both axonal release of neurotransmitters and postsynaptic responsiveness of target neurons to afferent input through activation of extrasynaptic MOR.

Amino Acid Sequence↗

Selective in vivo tumor localization of heptacarboxylic porphyrin isomer I in a bladder tumor model: a novel technique to modulate porphyrin localization.

We were the first to report that uroporphyrin isomer I is a superior tumor localizer when compared with hematoporphyrin derivative. In the present study, we have examined the tumor localization of heptacarboxylic porphyrin isomer I (hepta-P) using a bladder tumor model. We have also compared it to that found with uroporphyrin isomer I (Uro-P). We now show, for the first time, that (hepta-P) isomer I can be selectively retained in bladder malignant cells, a novel observation which has not yet been described by other investigators. Furthermore, we have provided a novel technique to modulate and manipulate blood protein binding to porphyrin in a controlled manner, such that the tumor localization properties can be effectively utilized without prolonged retention in the skin and to produce high uptake in the tumor, i.e., a higher therapeutic ratio. The biodistribution of hepta-P in different organs is presented.

Animals↗

A noninvasive method to estimate arterial impedance by means of assessment of local diameter change and the local center-line blood flow velocity using ultrasound.

Vascular impedance is defined as the ratio between the frequency components of the local blood pressure waveform and those of the local blood volume flow waveform. Assessment of vascular impedance is, for example, important to study heart load and distal vascular bed vasomotricity. However, only a few studies on vascular impedance have been performed in humans because pulsatile pressure and volume flow waveforms, simultaneously recorded at the same location, are difficult to obtain noninvasively. The noninvasive assessment of arterial impedance as described in this study is based on the replacement of the pressure waveform by the distension (change in diameter) waveform and the volume flow waveform by the center-line blood flow velocity waveform. Both waveforms can simultaneously and accurately be assessed by means of pulsed ultrasound. It will be shown that, depending on the Womersley number, the volume flow waveform may be replaced by the center-line blood flow velocity waveform for a given frequency range and that the pressure waveform may be replaced by the distension waveform for a wide frequency range. The validation of the proposed ultrasound method was performed through an in vitro study in a flow model with a distensible tube terminated with a hydraulic load (modified windkessel model). It is shown that, in vitro, the proposed method gives the same results as the local spectral pressure-flow relationship.

Arteries↗

A mechanism of peripheral spread or localization of inflammatory reactions--role of the localized ground substance adaptive phenomenon.

It is known that connective tissue-active peptides (CTAP) are released at sites of inflammation. Some of this material diffuses to immediately adjacent tissue and increases ground substance viscosity and fibroblast proliferation. This contributes to host protection against spread of infections and tumors. In a person with normal inflammatory reactivity, it should prevent spread of mediators and products of local inflammation. However, the host with an increased reactivity in sites of increased ground substance viscosity or who is highly reactive to dilution of tissue fluid would respond with more inflammation. A non-infectious, non-malignant process in a host with a highly reactive inflammatory or immune response could end up with peripheral spread. This could occur in any tissue but it occurs with great vigor in the skin. It could present as a peripheral extension of a local disease process, such as psoriasis, or the migration of cyclic lesions with clearing of the central area. There are over a dozen variants of peripherally spreading, ringed lesions described in the dermatologic literature. This includes erythema marginatum of rheumatic fever, erythema gyratum repens associated with cancer, and erythema annulare centrificum associated with allergic reactions to fungi. Many of the ringed dermatologic lesions have an immunologic component. They tend to be associated with inflammatory immune reactions at distant sites. Dermatologists have been gathering information on the ringed phenomenon at least since Hebra in 1854. The acute localized ground substance adaptive phenomenon is a broadly beneficial biologic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗