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PubMed2005

[Local relapse in young (< or = 40 years) women with breast cancer after mastectomy or breast conserving surgery: 15-year results].

PURPOSE: Data from various sources indicate that after breast conserving surgery (BCS), younger patients have a high risk of local relapse, but there is insufficient evidence about the risk of post-mastectomy local recurrence. This study investigates the risk of local recurrence for young (< or = 40 years) patients treated with either conservative or radical surgery, with or without radiotherapy (RT). METHODS: 148 young (< or = 40 years) women with early invasive breast cancer underwent axillary dissection and mastectomy (n = 92) or BCS (n = 56) between January 1983 and December 1997. When adjuvant RT was given, the median dose was 50 Gy. The risk factors of local recurrence were estimated by uni- and multivariate analysis. RESULTS: At a median follow-up time of 199 months 60 (40.5%) women died of breast cancer. The type of surgery (mastectomy vs. wide tumour excision) had no significant impact on breast cancer-specific survival. The crude rate of local relapse for nonirradiated mastectomy and BCS patients was 24% and 75% (p = 0.0041), and for irradiated patients 4% and 23%, respectively (p = 0.0091). After mastectomy in univariate analysis nodal status (negative vs. positive) and RT (no vs. yes) were significant predictors of local control, but tumour size (T1 vs. T2) and histological grade (1-2 vs. 3) were not. In multivariate analysis both nodal involvement and omission of RT remained independent significant negative predictors of local control. After BCS in univariate analysis extensive intraductal component (EIC, negative vs. positive) and RT (no vs. yes) were significant predictors of local control, but tumour size (T1 vs. T2), nodal status (N0 vs. N1) and histological grade (1-2 vs. 3) were not. In multivariate analysis omission of RT and presence of EIC remained independent significant negative predictors of local control. The 15-year actuarial rate of local relapse was 29% for irradiated, and 75% for nonirradiated BCS patients (RR, 0.21; 95% CI, 0.07-0.55; p = 0.0052). The 15-year actuarial rate of local recurrence was 6% for irradiated, and 46% for nonirradiated node-positive mastectomy patients (RR, 0.12; 95% CI, 0.06-0.96; p = 0.0095). CONCLUSION: The incidence of local recurrence is high for young patients treated either with BCS or mastectomy, and RT significantly reduces the risk. The use of postmastectomy RT in node-positive patients gives a good local control. The efficacy of BCS and RT as a treatment modality for young patients needs further investigations.

Actuarial Analysis↗
PubMed2000

Utilization of local anesthesia by Arkansas dental hygienists, and dentists' delegation/satisfaction relative to this function.

PURPOSE: Given the legalization of administration of local anesthesia as an expanded function for dental hygienists in Arkansas, the purpose of this study was to 1) describe the utilization of local anesthesia in dental hygiene care; 2) compare the utilization of local anesthesia by dental hygienists certified in the administration of local anesthesia and those who were not; 3) determine if there was a difference in attitude toward the use of local anesthesia for dental hygiene procedures between dental hygienists certified in the expanded function versus those not certified; 4) determine if and to what degree employers delegate this procedure to certified employees; and 5) compare employer satisfaction with this expanded function for those who employed a certified dental hygienist and those who did not. METHODS: Surveys were sent to all Arkansas dental hygienists certified, as of June 1998, to administer local anesthesia as well as an equal random sample of Arkansas dental hygienists not certified in the expanded function. The dentist employers of these dental hygienists also were asked to complete a companion survey. These surveys included demographic items as well as questions about the demand for and utilization of local anesthesia by dental hygienists. Additionally, the surveys included an opinionnaire section concerning attitudes toward and perceptions of the administration of local anesthesia by dental hygienists. RESULTS: An overall response rate of 31% (n = 182) was achieved for the survey of the dental hygienist sample (n = 580). Forty-one percent of the surveys (n = 118) were returned by the dental hygienists certified in the administration of local anesthesia, while 22% (n = 64) of the surveys were returned by those not certified in the function. An approximate response rate of 25% (n = 146) was achieved for the surveys of the dentist employers. Findings indicate that the respondents perceived local anesthesia as beneficial for both dental hygiene patients and clinicians. Arkansas dental hygienists and dentists reported that this function had a positive impact on scheduling, production, patient satisfaction and comfort, and quality of care. Furthermore, more than nine out of 10 of the dentist respondents were satisfied with their dental hygienists local anesthesia skills and/or would encourage their uncertified dental hygienists to become certified. Dental hygienists certified in the function reported utilizing this technique moderately to fully for patient care, particularly for those in practices with greater numbers of periodontally involved patients. Certified dental hygienists also viewed local anesthesia as contributing to the quality of patient care and necessary for dental hygiene procedures. CONCLUSIONS: Results of this study provide evidence that local anesthesia benefits dental hygiene patients and clinicians. Both Arkansas dental hygienists and dentists viewed this expanded function as necessary for provision of quality dental hygiene care. The dentist employers of certified dental hygienists reported that the function had a positive impact on scheduling, production, patient satisfaction and comfort, and quality of care.

Anesthesia, Dental↗
PubMed2002

Identification of cis elements which direct the localization of maternal mRNAs to the posterior pole of ascidian embryos.

During ascidian embryogenesis, some mRNAs show clear localization at the posterior-most region. These postplasmic mRNAs are divided into two groups (type I and type II) according to their pattern of localization. To elucidate how these localization patterns are achieved, we attempted to identify the localization elements of these mRNAs. When in vitro synthesized postplasmic mRNAs were introduced into eggs, these mRNAs showed posterior localization similar to the endogenous mRNAs. The posterior localization of these mRNAs was mediated by their 3' untranslated regions (3' UTRs), as is the case for several localized Drosophila and Xenopus mRNAs. We identified smaller fragments of the 3' UTRs of HrWnt-5 and HrPOPK-1 mRNAs (type I) and HrPet-3 mRNA (type II) that were sufficient to direct green fluorescent protein mRNA to the posterior pole. For the localization of HrWnt-5 mRNA, two UG dinucleotide repetitive elements were essential. Motifs similar to these small elements also exist within the HrPOPK-1 mRNA localization element and 3' UTR of HrZF-1 mRNA, suggesting the conservation of localization elements among type I mRNAs. In contrast, the smallest sequence that suffices for the posterior localization of HrPet-3 (a type II mRNA) has different features from those of type I mRNAs; indeed, it does not have an identifiable critical element. This difference may distinguish type II mRNAs from type I mRNAs. These findings, especially the identification of the small localization element of HrWnt-5 mRNA, provide new insights into the localization of mRNAs during ascidian embryogenesis.

3' Untranslated Regions↗
PubMed1995

Locally challenging osteo- and chondrogenic tumors of the axial skeleton: results of combined proton and photon radiation therapy using three-dimensional treatment planning.

PURPOSE: Tumors of the axial skeleton are at high risk for local failure. Total surgical resection is rarely possible. Critical normal tissues limit the efficacy of conventional photon therapy. This study reviews our experience of using combined high dose proton and photon radiation therapy following three-dimensional (3D) treatment planning. METHODS AND MATERIALS: Between December 1980 and September 1992, 47 patients were treated at the Massachusetts General Hospital and Harvard Cyclotron Laboratory for primary or recurrent chordomas and chondrosarcomas (group 1, 20 patients), osteogenic sarcomas (group 2, 15 patients) and giant cell tumors, osteo-or chondroblastomas (group 3, 12 patients). Radiation treatment was given postoperatively in 23 patients, pre- and postoperatively in 17 patients, and 7 patients received radiation therapy as definitive treatment modality following biopsy only. The proton radiation component was delivered using a 160 MeV proton beam and the photon component using megavoltage photons up to 23 MV energy with 1.8-2.0 Cobalt Gray Equivalent (CGE) per fraction, once a day. Total external beam target dose ranged from 55.3 CGE to 82.0 CGE with mean target doses of 73.9 CGE (group 1), 69.8 CGE (group 2), and 61.8 CGE (group 3). RESULTS: Group 1 (chordoma and chondrosarcoma): Five of 14 patients (36%) with chordoma recurred locally, and 2 out of 5 patients developed distant metastasis, resulting in 1 death from disease. A trend for improved local control was noted for primary vs. recurrent tumors, target doses > 77 CGE and gross total resection. All patients with chondrosarcoma achieved and maintained local control and disease-free status. Five-year actuarial local control and overall survival rates were 53% and 50% for chordomas and 100% and 100% for chondrosarcomas, respectively. Group 2 (osteogenic sarcoma): Three of 15 patients (20%) never achieved local control and died within 6 months of completion of radiation treatment. Only 1 out of 12 patients who were controlled for more than 6 months failed locally, yielding a 5-year local control rate of 59% for 15 patients. Overall, 4 patients (27%) developed distant metastasis (two in patients with uncontrolled primary); 4 patients succumbed to their disease, 3 patients died of intercurrent disease, resulting in overall survival of 44% at 5 years. Group 3 (giant cell tumors, osteo- and chondroblastoma): One of 8 patients with giant cell tumor failed locally, 1 patient distantly, and all patients are alive. Three of 4 patients with osteo- or chondroblastoma are alive and well. One patient suffered local recurrence and died of disease. Local control rate and overall survival for this group of 12 patients was 76% and 87% and local control for patients with giant cell tumors 83% at 5 years. In the majority of cases radiotherapy was well tolerated. However, one patient with a large base of skull tumor developed retinopathy, one patient required enucleation of a previously blind eye, and another patient with sacral tumor developed chronic diarrhea. CONCLUSION: Combined proton and photon radiation therapy optimized by 3D treatment planning, allows the delivery of higher radiation doses to tumors of the axial skeleton, while respecting normal tissue constraints. High radiation doses can result in improved long-term local control.

Adolescent↗
PubMed2004

Long-term results using local excision after preoperative chemoradiation among selected T3 rectal cancer patients.

PURPOSE: To assess the pelvic failure among patients with T3 rectal cancer treated with local excision after preoperative chemoradiation. METHODS AND MATERIALS: Between January 1990 and June 2002, 431 patients with clinically staged T3 rectal cancer were treated with preoperative chemoradiation followed by surgical resection. Full-thickness local excision [Kraske (n = 3) or a transanal excision (n = 23)] was performed in 26 patients because of patient refusal of abdominoperineal resection (APR) (n = 13), medical comorbidity (n = 4), physician preference after a complete clinical response (n = 6), and other reasons (n = 3). All patients were treated with continuous-infusion 5-fluorouracil (5-FU) (300 mg/m(2) Monday to Friday) and concomitant pelvic radiation (45 Gy in 25 fractions with a 3-field belly board technique). Ten local-excision patients received a concomitant boost during the last week of therapy (1.5-Gy second daily fractions) for a total dose of 52.5 Gy. Similar preoperative treatment was followed by total mesorectal excision in 405 patients. Among the local-excision patients, the median tumor size was 3.5 cm (range, 0.5-7 cm). Well-differentiated or moderately-differentiated histology was present in all but 3 cases, and endoscopic ultrasound staging examination was performed in 25 of 26 patients. Based on CT findings, 1 patient was node positive. The median circumference involved by tumor was 33%, (20%-75%). The median distance from the anal verge was 3 cm (range, 1-8 cm). RESULTS: The mean follow-up was 46 months (range, 5-109 months) in the local-excision group. In the local-excision group, 19 of 26 patients had only residual scarring noted on digital rectal examination and rigid proctoscopy before surgery. Fourteen patients (54%) had a complete histologic response to chemoradiation, 9 patients (35%) had microscopic residual disease, and 3 patients (12%) had gross residual disease. Two intrapelvic recurrences occurred at 76 and 20 months among the 26 patients treated with local excision (6% 5-year actuarial pelvic recurrence rate). This rate compared with an 8% 5-year actuarial pelvic recurrence rate among T3 patients treated with mesorectal excision and a 6% pelvic recurrence rate in the subgroup of mesorectal-excision patients with a complete clinical response to preoperative chemoradiation. One additional local-excision patient recurred in an inguinal lymph node after local excision and subsequently died of metastatic disease. A total of 2 local-excision patients died of metastatic rectal cancer. Actuarial overall survival at 5 years was 86% in the local-excision group compared with 81% among mesorectal-excision patients (p = NS), and 85% in patients with a complete clinical response to chemoradiation followed by mesorectal excision by APR or LAR (p = NS). CONCLUSIONS: In an experience stimulated by patient refusal of APR, highly selected patients who responded well to conventional external-beam radiotherapy (CXRT) were selected to undergo local excision. Most of these patients had pathologic complete response. Local control and survival rates are comparable to those achieved with chemoradiation followed by mesorectal excision. This strategy should be prospectively studied in a group of patients with low rectal cancer who have no clinical evidence of tumor after chemoradiation.

Adenocarcinoma↗
PubMed2005

Radiotherapy for local control of osteosarcoma.

PURPOSE: Local control of osteosarcoma in patients for whom a resection with satisfactory margins is not achieved can be difficult. This study evaluated the efficacy of radiotherapy (RT) in this setting. METHODS AND MATERIALS: We identified 41 patients in our sarcoma database with osteosarcomas that either were not resected or were excised with close or positive margins and who underwent RT with external beam photons and/or protons at our institution between 1980 and 2002. Patient charts were reviewed to assess local control, progression-free survival, metastasis-free survival, and overall survival. RESULTS: The anatomic sites treated were head/face/skull in 17, extremity in 8, spine in 8, pelvis in 7, and trunk in 1. Of the 41 patients, 27 (65.85%) had undergone gross total tumor resection, 9 (21.95%) subtotal resection, and 5 (12.2%) biopsy only. The radiation dose ranged from 10 to 80 Gy (median 66). Twenty-three patients (56.1%) received a portion of their RT with protons. Chemotherapy was given to 35 patients (85.4%). Of the 41 patients, 27 (65.85%) were treated for localized disease at primary presentation, 10 (24.4%) for local recurrence, and 4 (9.8%) for metastatic disease. The overall local control rate at 5 years was 68% +/- 8.3%. The local control rate according to the extent of resection was 78.4% +/- 8.6% for gross total resection 77.8% +/- 13.9% for subtotal resection, and 40% +/- 21.9% for biopsy only (p < 0.01). The overall survival rate according to the extent of resection was 74.45% +/- 9.1% for gross total resection, 74.1% +/- 16.1% for subtotal resection, and 25% +/- 21.65% for biopsy only (p < 0.001). Patients with either gross or subtotal resection had a greater rate of local control, survival, and disease-free survival compared with those who underwent biopsy only at 5 years (77.7% +/- 7.5% vs. 40% +/- 21% [p <0.001], 73.9% +/- 8.1% vs. 25% +/- 21.6% [p <0.001], and 51.9% +/- 9.1% vs. 25% +/- 21.6% [p <0.01], respectively). Overall survival was better in patients treated at primary presentation (78.8% +/- 8.6% compared with 54% +/- 17.3% for recurrence) p <0.05). No definitive dose-response relationship for local control of tumor was seen, although the local control rate was 71% +/- 9% for 32 patients receiving doses > or =55 Gy vs. 53.6% +/- 20.1% for 9 patients receiving <55 Gy (p = 0.11). Of 15 patients with tumors >5.3 cm, 9 received doses > or =55 Gy and the local control rate was 80% +/- 17.9%, and 6 received doses <55 Gy with a local control rate of only 50% +/- 25% at 5 years (p = 0.16). Among patients who underwent gross total resection, the local control rate was 77.5% +/- 9.95% in 22 patients with negative margins vs 66.7% +/- 27.2% in 3 patients with positive margins (p = 0.54). Two patients had unknown margin status. CONCLUSION: RT can help provide local control of osteosarcoma for patients in whom surgical resection with widely, negative margins is not possible. It appears to be more effective in situations in which microscopic or minimal residual disease is being treated.

Adolescent↗
PubMed2000

Local reactions during allergen immunotherapy do not require dose adjustment.

BACKGROUND: The recent World Health Organization position paper on allergen immunotherapy states that local reactions to immunotherapy are not predictive of subsequent systemic reactions. Nevertheless, in clinical practice dose adjustment after local reactions continues to be recommended, presumably in an effort to prevent future systemic reactions. OBJECTIVE: We sought to determine whether dose adjustment versus no adjustment for local reactions during allergen immunotherapy influences the occurrence of subsequent systemic reactions. METHODS: In a single-site allergy clinic before October 1, 1997, local reactions after allergen vaccine injection resulted in adjustment of the subsequent dose. After October 1, 1997, no dose adjustments were made for immediate and late local reactions. For the same 9-month period before and after the change in local reaction dose-adjustment policy, systemic reaction rates were compared retrospectively. For individuals experiencing a systemic reaction, local reaction rates and local reactions immediately preceding a systemic reaction were also compared before and after the policy change. RESULTS: Comparing the 9-month period (October 1996-June 1997) preceding the policy change and the 9 months (October 1997-June 1998) after the change in policy, the systemic reaction rates (0.80% and 1.01%, respectively) were not statistically different (P =.24). Among those experiencing a systemic reaction, the rate of local reactions was unchanged (7.3% and 4.7%, respectively; P =.07), and the rate of local reactions immediately preceding a systemic reaction did not increase (18.8% and 10.5%, respectively; P =.37). The sensitivity of a local reaction predicting a systemic reaction at the next immunotherapy dose was 15%. CONCLUSIONS: A local reaction is a very insensitive predictor for a subsequent systemic reaction at the next allergen vaccine dose. Dose adjustment for most local reactions is unnecessary and may delay therapy, increase costs, and put the patient at increased risk of dose administration errors.

Adult↗
PubMed2002

Segmentation and selection contribute to local processing in hierarchical analysis.

The present study examined the role of segmentation and selection processes when we respond to local elements in hierarchical stimuli. The ease of segmentation and selection of an individual local element from hierarchical patterns was manipulated by making one local element substantially distinct from the others in colour. Experiment 1 showed that, when attention was spread across the global and local levels in a divided attention task, the introduction of the local red element speeded responses to local targets but slowed responses when targets appeared at the global level. Experiment 2 used a selective attention task in which subjects responded only to the local or the global shapes across a block of trials. Under these circumstances, the local red element reduced global-to-local interference in addition to speeding local responses. The results suggest that the efficiency with which local elements are segmented and selected affects responses to local aspects of hierarchical patterns; furthermore, the effect of local pop-out on global processing is contingent on top-down attentional control settings.

Adolescent↗
PubMed2006

PLPD: reliable protein localization prediction from imbalanced and overlapped datasets.

Subcellular localization is one of the key functional characteristics of proteins. An automatic and efficient prediction method for the protein subcellular localization is highly required owing to the need for large-scale genome analysis. From a machine learning point of view, a dataset of protein localization has several characteristics: the dataset has too many classes (there are more than 10 localizations in a cell), it is a multi-label dataset (a protein may occur in several different subcellular locations), and it is too imbalanced (the number of proteins in each localization is remarkably different). Even though many previous works have been done for the prediction of protein subcellular localization, none of them tackles effectively these characteristics at the same time. Thus, a new computational method for protein localization is eventually needed for more reliable outcomes. To address the issue, we present a protein localization predictor based on D-SVDD (PLPD) for the prediction of protein localization, which can find the likelihood of a specific localization of a protein more easily and more correctly. Moreover, we introduce three measurements for the more precise evaluation of a protein localization predictor. As the results of various datasets which are made from the experiments of Huh et al. (2003), the proposed PLPD method represents a different approach that might play a complimentary role to the existing methods, such as Nearest Neighbor method and discriminate covariant method. Finally, after finding a good boundary for each localization using the 5184 classified proteins as training data, we predicted 138 proteins whose subcellular localizations could not be clearly observed by the experiments of Huh et al. (2003).

Algorithms↗
PubMed1995

Prolongation of conduction time during premature stimulation in the human atrium is primarily caused by local stimulus response latency.

BACKGROUND: Conventional clinical electrophysiological techniques cannot accurately differentiate between local stimulus response latency and propagation time of the atrial response. The purpose of this study was to identify and distinguish local stimulus response latency from impulse propagation time in the human right atrium during programmed electrical stimulation. METHODS: Pacing was performed from two atrial sites (high and low right atrium) in 19 patients, using monophasic action potential recording/pacing combination catheters (interelectrode distance < 2 mm). Local stimulus response latency (interval between stimulus artifact and upstroke of the local monophasic action potential), and propagation time (interval between local and remote monophasic action potential upstroke) were evaluated at a basic cycle length (S1-S1) of 600 ms and as a function of the extrastimulus proximity (interval between extrastimulus and effective refractory period). Data are presented as means +/- SEM. RESULTS: During basic stimulation, local latency was very small (3.8 +/- 1.7 ms). During premature extrastimulation (proximity < 70 ms), local latency increased progressively with decreasing coupling intervals. Prolongation of local latency was most pronounced during stimulation close to the effective refractory period with local stimulus response latency increasing to 18.3 +/- 1.4 ms (380 +/- 7.9%) at 10 ms proximity (P < 0.002) and to 27.9 +/- 3.7 ms (630 +/- 13.2%) at 5 ms proximity, respectively (P < 0.0001). The impulse propagation time between the stimulation site and the remote recording site was on average 54.5 +/- 14.3 ms during basic stimulation, and increased up to 62.1 +/- 13.5 ms (14.0 +/- 8.4%), which was not significant. CONCLUSIONS: The intra-atrial impulse propagation remained essentially unchanged during the entire range of premature stimulation. Local stimulus response latency was negligible and constant during late coupling intervals but increased dramatically when extrastimulation approached the preceding repolarization phase. This has the following clinical impact: first, local stimulus response latency during premature extrastimulation curbs the targeted atrial response interval second, local stimulus response latency, not propagation time, seems responsible for the greater functional than effective refractory period during electrical stimulation; third, local stimulus response latency should be considered in pace mapping for accurate comparison of conduction time before pacing with that during pacing.

Aged↗
PubMed2005

Localized contractions in the normal human bladder and in urinary urgency.

OBJECTIVE: To describe an observational study to establish whether localized activity arises in the normal human bladder, and whether there is any correspondence between changes in such activity and reported sensation. PATIENTS, SUBJECTS AND METHODS: The generation of sensory information by the bladder depends on afferent stimulation by increased tension within the bladder wall. Autonomous bladder activity is apparent in several species, which is often localized and multifocal, giving rise to localized areas of stretch. Thus afferent activity may partly result from localized distortions of the bladder wall. Fourteen women patients presenting with increased bladder sensation during filling-phase cystometry were compared with six asymptomatic women volunteers. Localized bladder activity was assessed by the micromotion detection (MMD) method, using eight electrodes mounted on a Silastic balloon; local displacements of the electrodes were recorded as changes in electrical resistance, which were used to compute changes in the distance between each pair of electrodes. RESULTS: In two of the six volunteers, micromotions were seen in the extraperitoneal (ventral) portion of the bladder. Women with increased sensation on filling cystometry had a significantly higher prevalence of localized activity than the control group during MMD recording. The localized activity was more sustained and at a higher frequency than in asymptomatic women. All nine women reporting urinary urgency during MMD recording had localized contractile activity, while only four had phasic increases in detrusor pressure during the episodes of urgency. CONCLUSIONS: By measuring localized contractions within the bladder wall, we established a significant difference in the prevalence of localized activity between the groups studied, but there was no objective difference with conventional urodynamic studies. There was also a difference in the character of the localized contractions, with the exaggerated activity in the symptomatic group corresponding with the reported sensations. These findings suggest that localized distortion of the bladder wall stimulates afferent activity, and that the human detrusor may be functionally modular.

Adult↗
PubMed2005

Disparate subcellular localization patterns of Pseudomonas aeruginosa Type IV pilus ATPases involved in twitching motility.

The opportunistic pathogen Pseudomonas aeruginosa expresses polar type IV pili (TFP), which are responsible for adhesion to various materials and twitching motility on surfaces. Twitching occurs by alternate extension and retraction of TFP, which arise from assembly and disassembly of pilin subunits at the base of the pilus. The ATPase PilB promotes pilin assembly, while the ATPase PilT or PilU or both promote pilin dissociation. Fluorescent fusions to two of the three ATPases (PilT and PilU) were functional, as shown by complementation of the corresponding mutants. PilB and PilT fusions localized to both poles, while PilU fusions localized only to the piliated pole. To identify the portion of the ATPases required for localization, sequential C-terminal deletions of PilT and PilU were generated. The conserved His and Walker B boxes were dispensable for polar localization but were required for twitching motility, showing that localization and function could be uncoupled. Truncated fusions that retained polar localization maintained their distinctive distribution patterns. To dissect the cellular factors involved in establishing polarity, fusion protein localization was monitored with a panel of TFP mutants. The localization of yellow fluorescent protein (YFP)-PilT and YFP-PilU was independent of the subunit PilA, other TFP ATPases, and TFP-associated proteins previously shown to be associated with the membrane or exhibiting polar localization. In contrast, YFP-PilB exhibited diffuse cytoplasmic localization in a pilC mutant, suggesting that PilC is required for polar localization of PilB. Finally, localization studies performed with fluorescent ATPase chimeras of PilT and PilU demonstrated that information responsible for the characteristic localization patterns of the ATPases likely resides in their N termini.

Adenosine Triphosphatases↗
PubMed2001

Localization of distributed sources and comparison with functional MRI.

Functional mapping of the human brain has made tremendous progress in the past years thanks to new technical developments. Imaging methods are now available; they allow to study brain functions with high spatial and temporal resolution. Single photon emission computer tomography (SPECT), positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and high resolution electro- and magnetoencephalography (EEG and MEG) are currently intensively applied techniques to functional studies, each one having specific properties concerning spatial and temporal resolution. The success of these methods in basic neuroscience research has led to the demand for applying them to clinical questions. Diseases of the central nervous system that lead to brain dysfunction can be ideally explored using these techniques. Of particular importance are those diseases in which a focal neuronal dysfunction is the primary cause and where surgical resection of this focus might be the cure. This is often the case for epilepsy, where a discrete primary focus might exist from which pathological rhythms evolve and propagate throughout the brain, leading to seizures that severely handicap the patient. Surgical resection of the primary focus is only possible if the focus can be exactly localized and adequately separated from functionally important areas. This is where these new functional imaging tools become important. The use of SPECT and PET for focus localization has been most extensively studied and their specificity and sensitivity are intensively discussed. In the last few years functional MRI has evolved as a new interesting tool in epileptic focus localization. The most important limitation of these techniques, however, is the temporal resolution. Since epileptic activity can propagate very fast, several hyper- or hypoactive regions are seen in the images and primary areas cannot be distinguished from regions of propagation. The only methods that have sufficient temporal resolution to follow neuronal activity in real time are the electrophysiological measures, i.e. the EEG and the MEG. Localization of the sources in the brain that produced a given surface electromagnetic field has become possible through algorithms that solve the so-called "inverse problem". Several different algorithms exist and many groups begun to apply them to epileptic data with the aim to localize the focus of the pathological electrical discharges. This review article discusses the use of distributed EEG source localization procedures in the presurgical evaluation of patients with intractable focal epilepsy. In contrast to equivalent dipole models, distributed localization methods do not localize one active point in the brain but rather assume extended active areas, which is generally the case in epileptic activity. The methods shown here are based on linear numerical methods and are therefore less prone to errors when working with scattered solution spaces such as the one defined by anatomical constraints. Solutions constraint to the gray matter determined in the individual MRI are shown here. We illustrate three methods to increase the spatial resolution of the source localization procedures: One is to increase the number of recording channels to more than 100, the second to use linear methods of high precision to detect focal sources (EPIFOCUS), and the third to combine EEG source localization with EEG-triggered functional magnetic resonance imaging. The importance of EEG source localization for the interpretation of fMRI data will be particularly discussed in view of the important difference of the temporal resolution by the two methods. The localization methods can be applied to interictal as well as to ictal activity. In case of analysis of ictal EEG we propose to use full scalp frequency analysis to determine the time period of seizure onset and to localize the sources of the initial dominant frequency.

Journal Article↗
PubMed1996

[Local anesthesia in operations of the head-neck area].

BACKGROUND: Many operations in the head and neck area can be performed under local anesthesia. However, the use of local anesthesia does not automatically reduce the risk for the patient undergoing surgery. RESULTS: In the present paper, the authors discuss local anesthetics used in surgical procedures in the head and neck region. Aminoesters are currently the most commonly used local anesthetics. Local anesthetics vary with respect to the onset and duration of the local anesthetic effect. The choice of local anesthetic depends on the estimated duration of the surgical procedure. Possible side effects of these substances may affect the central nervous as well as the cardiovascular system. Certain changes in serum electrolytes (i.e., hyperkalemia) as well as hypoxia and hypercapnia significantly increase the cardiotoxic potential of local anesthetics. Different vasoconstrictor agents are used in addition to local anesthetics to prolong the duration of the local anesthetic effect and to provide the surgeon with a nearly bloodless field. The two groups of vasoconstrictors used in these days are catecholamines (epinephrine) and vasopressin analogs. Systemic side effects of catecholamines include cardiovascular reaction, mainly in patients with typical risk factors (i.e., coronary heart disease, high blood pressure, or chronic heart failure). Vasopressin analogs produce fewer side effects than epinephrine. Even so, an overdose of these vasoconstrictors might still result in severe cardiac complications. The recommended maximum doses of these drugs should be strictly observed. CONCLUSIONS: For several reasons, local anesthesia has become popular for a variety of surgical procedures in the head and neck in recent years. Even though the use of local anesthetics and vasoconstrictors in head and neck procedures has its advantages for both the patient and the surgeon, the limitations for the use of these drugs must always be taken into consideration.

Anesthesia, Local↗
PubMed2006

Local Anesthesia With Monitored Anesthesia Care vs General Anesthesia in Thyroidectomy: A Randomized Study.

BACKGROUND: Early in the 20th century, thyroid surgery was performed using local anesthetic techniques. When general anesthesia became safer, surgeons started performing thyroidectomy exclusively under general anesthesia. However, recent descriptions of thyroidectomy under local anesthesia claim similar results to thyroidectomy under general anesthesia. Surgery conducted under local anesthesia can result in early discharge, ie, a hospital stay of less than 8 hours. HYPOTHESIS: Thyroidectomy can be performed under local anesthesia with monitored anesthesia care (MAC) with results similar to general anesthesia in an outpatient or inpatient surgery setting. DESIGN: A prospective randomized study comparing local anesthesia with MAC vs general anesthesia in adult patients undergoing thyroidectomy in a potential outpatient setting, defined as same-day discharge. Patients were excluded if they were not able to receive local or general anesthesia. In addition, we performed an outcome evaluation of the use of local anesthesia with MAC for thyroidectomy and the use of outpatient surgery for thyroidectomy. We compared 58 consecutive thyroidectomies performed prior to the study with 58 consecutive thyroidectomies performed after the study. SETTING: A 486-bed university-affiliated hospital. RESULTS: Fifty-eight patients undergoing thyroidectomy received random assignment: 29 to local anesthesia with MAC and 29 to general anesthesia under study protocol. Fifty-one surgical procedures (88%) were completed as outpatient surgery. No significant differences were found between the 2 study groups in demographics, postoperative adverse symptoms, complications, hospital admission, or patient satisfaction. Patients in the general anesthesia group spent, on average, more time postoperatively than patients in the group that received local anesthesia with MAC in the outpatient surgery center until same-day discharge (P = .02). When compared before the study, we found a significant increase after the randomized study in the use of local anesthesia with MAC (P<.001) and outpatient thyroidectomies (P<.001). CONCLUSIONS: Thyroidectomy can be performed in the studied patient population under either general anesthesia or local anesthesia with MAC, expecting similar operative results, clinical results, and patient satisfaction. In addition, local anesthesia with MAC can reduce the postoperative time spent in an outpatient surgery setting with potential health care cost savings.

Adult↗
PubMed1986

Localized, operable soft tissue sarcoma of the lower extremity.

Recent developments in adjuvant treatment of soft tissue sarcomas of the extremities have altered the surgical approach to this disease. To assess the effects of changing management on local recurrence rates and to examine factors governing local failure, we reviewed the records of 315 adults with operable, nonmetastatic soft tissue sarcoma of the lower extremity who were treated at one institution over a ten-year period. The median follow-up was 8.2 years. One third of our patients presented with locally recurrent tumors after initial treatment elsewhere. Sixty-six percent of the lesions were above the knee, and 60% were high grade. Two thirds of the patients underwent limb-sparing surgery (LSS), which in the latter half of the study period outnumbered amputations by four to one. Local recurrence was directly related to the adequacy of the surgical margins. Adjuvant radiotherapy and chemotherapy did not significantly decrease local recurrence in patients who underwent LSS, although favorable trends were observed. A significantly increased risk of local failure was associated with age greater than 53 years, presentation with local recurrence, high tumor grade, deep location, positive nodes, and less than adequate surgical margins. Local failure also varied significantly with histologic type and was highest in patients with embryonal rhabdomyosarcoma and neurofibrosarcoma. Improved local control, particularly in patients with high-grade tumors, was observed in the latter half of the study period despite the increased use of LSS. When the data were subjected to multivariate analysis, the following variables emerged as independent predictors of local failure: age greater than 53 years, presentation with local recurrence, high grade, less than adequate margins, embryonal rhabdomyosarcoma, and neurofibrosarcoma. The key to local control of sarcomas of the extremities is resection of the tumor with adequate margins. The role of adjuvant treatment, particularly following LSS, is still being evaluated. The risk factor profile should be considered when selecting a treatment program for patients with lower extremity sarcomas.

Adolescent↗
PubMed2003

Relation between the method of detection of initial breast carcinoma and the method of detection of subsequent ipsilateral local recurrence and contralateral breast carcinoma.

BACKGROUND: Mammography and physical examination are routine methods for the detection of ipsilateral local recurrence and contralateral breast carcinoma in patients initially undergoing breast conservation treatment. The current study reports the relation between the method of detection of the initial breast carcinoma and the method of detection of subsequent ipsilateral local recurrence and contralateral breast carcinoma. METHODS: A retrospective review was performed of the records of female patients with initial American Joint Committee on Cancer (AJCC) Stage I and II invasive breast carcinoma who developed ipsilateral local recurrence or contralateral breast carcinoma after breast conservation treatment. The method of detection of local recurrence in the ipsilateral breast and the method of detection of contralateral breast carcinoma were compared with the method of detection of the primary tumor. RESULTS: There were 125 ipsilateral breast local recurrences and 71 contralateral breast carcinoma cases detected. Of the 125 recurrences in the ipsilateral breast, 38% (48 recurrences) were detected by mammography only, 37% (46 recurrences) were detected by physical examination only, and 25% (31 recurrences) were detected by both methods. Of the 71 contralateral breast carcinoma cases, 53% (38 cases) were detected by mammography only, 23% (16 cases) were detected by physical examination only, and 24% (17 cases) were detected by both methods. When the primary tumors were detected by mammography only, 21% of the local recurrences (3 of 14 local recurrences) and 19% of the contralateral breast carcinoma cases (4 of 21 cases) were detected by physical examination only. When the primary tumors were detected by physical examination only, 24% of the local recurrences (14 of 58 local recurrences) and 42% of the contralateral breast carcinoma cases (8 of 19 cases) were detected by mammography only. When stratified by the interval between diagnosis of the primary tumor and ipsilateral local recurrence or contralateral breast carcinoma (< or = 5 years vs. > 5 years) or age of the patient at the time of ipsilateral breast recurrence or contralateral breast carcinoma (age < or = 49 years vs. age > or = 50 years), both breast examination and mammography were found to be important in the detection of locally recurrent tumor and contralateral breast carcinoma in each subgroup of the patients, regardless of the method of presentation of the primary tumor. CONCLUSIONS: Both mammography and physical examination were found to be significant in the detection of locally recurrent tumor in the ipsilateral breast and in the detection of contralateral breast carcinoma, regardless of the method of detection of the primary tumor.

Adult↗
PubMed1997

The relationship of local and distant failure from endometrial cancer: defining a clinical paradigm.

PURPOSE: Recently, statistical methods have been developed to rigorously assess the relationship between local and distant failures. Such methodology has successfully been applied to a variety of tumors including those arising in the prostate, breast, and cervix. To date, no published data are available to generate a hypothesis to characterize the relationship between local and distant failure for endometrial cancer. The present analysis was undertaken to determine the effect of locoregional control on subsequent metastatic dissemination among women with pathologically staged endometrial cancer treated by hysterectomy followed by adjuvant radiotherapy. METHODS: The series consisted of 394 patients with FIGO stages I-III endometrial cancer who were surgically staged prior to irradiation [median external beam dose 45 Gy +/- brachytherapy (median vaginal surface dose, 30 Gy)]. The duration of follow-up ranged from 2 to 151 months, with a median of 62 months. Multiple factors were evaluated to determine the associations with distant relapse including FIGO pathological stage, grade, histopathologic subtype (adeno vs papillary/papillary-serous/clear cell), depth of myometrial penetration, age, and local disease status. Time-dependent survival models were generated to assess the influence of local failure on distant metastases. RESULTS: For the entire series, the 5-year actuarial rates of local and distant failures were 9 and 20%, respectively. Women who failed locally had nearly a fourfold risk of failing distantly compared to those who remained locally controlled (P = 0.02). Moreover, the earlier a local failure developed (e.g., within 1 year vs within 3 years), the more likely it was to be associated with distant metastases (P < 0. 05). The univariate correlations of other factors with the 5-year rate of freedom from distant relapse also disclosed significant associations for grade, histology (adenoca vs papillary/papillary-serous/clear cell), and FIGO path stage. In multivariate analysis, only local control, low grade (grade 1 and 2), and early pathological stage were independently related to the likelihood of achieving freedom from distant relapse. CONCLUSIONS: Distant dissemination of endometrial cancer may develop secondary to local failure. Optimization of local control is therefore necessary if long-term cure is to be achieved. The limits of the current database cannot establish whether local failure is a cause of distant spread or a high-risk marker for metastases; however, ongoing national cooperative trials may resolve this controversy.

Actuarial Analysis↗