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PubMed2002

Surgical implications of neuromagnetic spike localization in temporal lobe epilepsy.

PURPOSE: To investigate the clinical usefulness of magnetoencephalography (MEG) as a guide to the surgical treatment of temporal lobe epilepsy (TLE). METHODS: Preoperative spike localization by MEG was compared with seizure outcome and postoperative spike localization at 12 months after resective surgery in 16 patients with TLE. Spike localization was classified into anterior temporal (AT) and non-AT localization in 11 patients without neocortical lesion treated with anterior temporal lobectomy (ATL); and lesion and lobar localization in five patients with neocortical lesion treated with lesionectomy (n = 3) or lesionectomy with medial temporal resection (n = 2). RESULTS: All five patients with AT localization became seizure free and spike free after surgery. Among the six patients with non-AT localization, two became seizure free and spike free, two became seizure free with residual spikes, one had residual seizures but no spikes, and one had both residual seizures and spikes. All three patients with lesion localization and two with lobar localization had favorable seizure outcome and became spike free after surgery. CONCLUSIONS: MEG spike localization can identify neocortical sources remote from the presumed epileptogenic area. Favorable seizure outcome can be expected in patients with AT localization after ATL and patients with lesion localization after lesionectomy. In contrast, non-AT localization indicates either nonmedial TLE or spike propagation to the posterior and extratemporal neocortex. Similarly, lobar localization indicates spike propagation from an epileptogenic lesion or extensive epileptogenicity. Patients with non-AT localization or lobar localization should undergo intensive evaluations, such as intracranial EEG, for improved seizure outcome.

Action Potentials↗
PubMed1983

Spiking local interneurons as primary integrators of mechanosensory information in the locust.

A population of spiking local interneurons in the metathoracic ganglion of the locust is vigorously excited by particular sensory stimuli from the hindlegs and participates in local postural reflexes. We examined the inputs from singly innervated mechanoreceptors (hairs and campaniform sensilla) to these spiking local interneurons, to nonspiking local interneurons, and to motor neurons that are also elements of local reflex pathways. Recordings were made intracellularly from the interneurons and motor neurons and extracellularly from afferent fibers. The physiological evidence is consistent with the spiking local interneurons being excited by direct, chemically mediated synaptic inputs from the afferents. Each afferent spike is followed at a constant latency by an excitatory postsynaptic potential (EPSP) in a spiking local interneuron, even at instantaneous frequencies as high as 300 Hz. The estimated synaptic delay is 1.5 ms, similar to that measured at other presumed monosynaptic connections within the same ganglion. Cobalt stains of individual interneurons, and of the central projections of afferent fibers show that both branch within the same ventral region of neuropil. Afferents from several hairs and campaniform sensilla converge on an individual spiking local interneuron. One interneuron is shown to receive inputs from at least seven hairs and four campaniform sensilla, but these represent only a tiny fraction of the total number of such sensilla on a hindleg. Practical limitations to the number of sensilla that can be tested for each interneuron means that the degree of convergence is likely to be considerably underestimated. We found no evidence that nonspiking local interneurons or motor neurons receive direct inputs from the afferents tested. Neurons of both types are, however, affected by stimulation of individual hairs, and the resulting pattern of postsynaptic potentials (PSPs) is similar to the pattern of spikes evoked in the spiking local interneurons. We infer from the evidence presented here and elsewhere (10, 11) that the spiking local interneurons are involved in at least two types of pathways for local interactions: 1) sensory neuron-spiking local interneuron-motor neuron, and 2) sensory neuron-spiking local interneuron-nonspiking local interneuron-motor neuron. We conclude that the spiking local interneurons are major elements in the primary integration of inputs from external receptors on the hindlegs.

Animals↗
PubMed1998

Negative regulation of local hepatocyte growth factor expression by angiotensin II and transforming growth factor-beta in blood vessels: potential role of HGF in cardiovascular disease.

Because hepatocyte growth factor (HGF) is a member of the endothelium-specific growth factors, we hypothesized that HGF may play a role in cardiovascular disease. Therefore we first examined the role of local HGF production in endothelial cell (EC) growth. Addition of anti-HGF antibody to EC resulted in a significant decrease in EC number. Moreover, coculture of vascular smooth muscle cells (VSMC) with EC resulted in an increase in EC number that was completely inhibited by anti-HGF antibody, suggesting that HGF secreted from EC and VSMC regulates EC growth in an autocrine-paracrine manner. Interestingly, transforming growth factor (TGF)-ss significantly decreased HGF secretion from EC, whereas interleukin 6 stimulated immunoreactive HGF secretion. In human VSMC, TGF-ss and angiotensin II suppressed local HGF production in a dose-dependent manner. Interestingly, anti-TGF-beta antibody resulted in significant but not complete inhibition of the decrease in local HGF production. To further study the regulation of local HGF production, we used a coculture system. Coculture of VSMC with EC resulted in a significant decrease in local HGF secretion. The decrease in local HGF production by coculture was significantly attenuated by anti-TGF-beta antibody, suggesting that inhibition of local HGF production in the coculture system was due to TGF-beta activation. Moreover, a further decrease in local HGF production in the coculture system by angiotensin II was also observed. Finally, we studied the role of angiotensin II in the regulation of the local HGF system in vivo by using a balloon injury rat model. Of importance, local HGF production was significantly decreased in balloon-injured arteries compared with intact vessels, accompanied by a reduction of HGF mRNA. An angiotensin-converting enzyme inhibitor (cilazapril) or an angiotensin II type 1 receptor antagonist (E-4177) significantly stimulated local vascular HGF production associated with the inhibition of neointimal formation after balloon injury compared with vehicle. In contrast, hydralazine did not alter local HGF production or neointimal formation despite decreasing blood pressure to a similar level as that in rats treated with cilazapril or E-4177. Overall, local HGF secretion from vascular cells was negatively regulated by TGF-beta and angiotensin II. The present study also demonstrated that blockade of angiotensin II significantly inhibited neointimal formation, accompanied by a significant increase in local vascular HGF production in vivo in the balloon injury model. Given the strong mitogenic activity of HGF on endothelial cells, increased local HGF production by blockade of angiotensin II may enhance reendothelialization after balloon injury. Downregulation of the local vascular HGF system by TGF-beta and vascular angiotensin may play an important role in the pathogenesis of cardiovascular diseases.

Angiotensin II↗
PubMed1999

Local resection of biliopancreatic cancer.

Biliopancreatic tumors that are potentially amenable to local resection include proximal bile duct tumors (Klatskin tumors), mid-choledochal duct tumors and tumors arising from the papilla of Vater. This paper reviews our experience in the AMC, with local resection of these conditions. From 1983-1997, 112 patients underwent surgical resection of a carcinoma of the hepatic duct confluence (Klatskin tumor). Local resection was undertaken in 80 patients (52 patients with type I and II tumors, and 28 patients with type III tumors) whereas in 32 patients with type III tumors, hilar resection was performed with liver resection. Negative surgical margins were achieved in 10 patients after local resection of type I and II tumors (19.2%), in 1 patient after local resection of a type III tumor (3.6%), and in 5 patients after hilar resection and liver resection (15.6%). Middle-third carcinomas of the extra-hepatic biliary tract are less common than proximal or distal bile duct tumors. From 1993-1998, 12 patients underwent resection of a mid-choledochal duct carcinoma. In 8 patients, local resection was performed and in 4 patients, subtotal pancreatoduodenectomy (PPPD) because of the close relationship of the tumor and the pancreas. Four patients had negative surgical margins, 2 after local resection (25%) and 2 after PPPD (50%). Although accepted for villous adenomas located in the ampulla, local resection for ampullary carcinoma is controversial. Nine patients underwent local resection of a presumed adenoma that proved to be an ampullary carcinoma. In 4 patients with T1 tumors, resection of the carcinoma was locally complete (44%). Additional PPPD was performed in 6 patients, including the 4 patients with complete local resections, showing no residual tumor at the previous site of excision, but, lymphnode metastases in two resection specimens (both of patients with presumed T1 tumors). Hence, local resection of a T1 ampullary carcinoma might result in tumor free margins, but does not deal with (usually retropancreatic) lymphnode metastases. In conclusion, local resection is applicable to Klatskin type I and II tumors. Local resection may be considered in the proximally located, mid-choledochal duct carcinomas but, when located closer to the pancreas, PPPD is the preferred treatment. For ampullary adenomas, local resection is feasible unless frozen section examination raises suspicion on a malignancy. Local resection of even limited ampullary carcinomas is not advisable because of lymphatic dissemination of the tumor and consequently, inadequate clearance.

Adolescent↗
PubMed2000

Epidural local anaesthetics versus opioid-based analgesic regimens on postoperative gastrointestinal paralysis, PONV and pain after abdominal surgery.

BACKGROUND: Gastrointestinal paralysis, nausea and vomiting, and pain, are major clinical problems following abdominal surgery. Anaesthetic and analgesic techniques that reduce pain and postoperative nausea and vomiting (PONV), and prevent or reduce postoperative ileus, may reduce postoperative morbidity, duration of hospitalisation and hospital costs. OBJECTIVES: To compare effects of postoperative epidural local anaesthetic with regimens based on systemic or epidural opioids, on postoperative gastrointestinal function, postoperative pain, PONV and surgical/anaesthetic complications. SEARCH STRATEGY: Trials were identified by computerised searches of the Cochrane Controlled Trials Register, MEDLINE, EMBASE and by checking the reference lists of trials and review articles. SELECTION CRITERIA: Randomised controlled trials comparing the effects of postoperative epidural local anaesthetic with systemic or epidural opioids. DATA COLLECTION AND ANALYSIS: Collected data included treatment in active (local anaesthetic) and control (opioid based) groups, time to first postoperative stool, time to first postoperative flatus, gastric emptying measured by the paracetamol absorption test, duration of the passage of barium sulphate, pain assessments, use of supplementary analgesics, nausea, vomiting and surgical/anaesthetic complications. MAIN RESULTS: Most studies in this review involved a small number of patients. Furthermore half of the studies indicated a poor level of methodology in particular regarding blinding and report of withdrawals. Heterogeneity of included studies was substantial. Results consistently showed reduced time to return of gastrointestinal function in the epidural local anaesthetic group compared with groups receiving systemic or epidural opioid (37 hours and 24 hours, respectively). Postoperative pain was comparable. Two studies compared the effect of epidural local anaesthetic with a combination of epidural local anaesthetic and opioid on gastrointestinal function. One study favoured epidural local anaesthetic and one study was indifferent. A meta analysis of five of eight studies comparing the effect of epidural local anaesthetic with a combination of epidural local anaesthetic and opioid on postoperative pain, yielded a reduction in VAS pain scores (0-100 mm) on the first postoperative day of 15 mm, in favour of the combination. No significant differences in PONV were observed between epidural local anaesthetic and opioid based regimens. REVIEWER'S CONCLUSIONS: Administration of epidural local anaesthetics to patients undergoing laparotomy reduce gastrointestinal paralysis compared with systemic or epidural opioids, with comparable postoperative pain relief. Addition of opioid to epidural local anaesthetic may provide superior postoperative analgesia compared with epidural local anaesthetics alone. The effect of additional epidural opioid on gastrointestinal function is so far unsettled. Randomized, controlled trials comparing the effect of combinations of epidural local anaesthetic and opioid with epidural local anaesthetic alone on postoperative gastrointestinal function and pain are warranted.

Abdomen↗
PubMed2001

Prognostic index for extremity soft tissue sarcomas with isolated local recurrence.

BACKGROUND: Local recurrence occurs in 10% to 20% of patients with extremity soft tissue sarcomas despite optimal treatment. The association of local recurrence with subsequent survival is controversial and conflicting. There is a need for a staging system to predict outcome in this subset of patients and also to plan optimal treatment, including adjuvant systemic therapy. METHODS: Data collected from 110 patients with locally recurrent extremity soft tissue sarcomas were studied. The influence of clinical and pathologic factors on local recurrence, distant metastasis, and disease-specific survival were analyzed by univariate and multivariate techniques. RESULTS: Of the 110 patients who presented with local recurrence, 92 had an isolated local recurrence and 18 had prior or concomitant distant metastases. The 5-year disease-specific survival for all patients was 63% and for those with isolated local recurrence, it was 69%. Histologic grade, malignant fibrous histiocytoma histology, pathologic margins, previous local recurrence, and prior radiotherapy were independent prognostic factors for subsequent local recurrence. Tumor size, histologic grade, and time to local recurrence were independent prognostic factors for distant metastasis and disease-specific survival. A prognostic index was calculated by assigning a score of 1 to 3 for each of the three independent prognostic factors for survival and added to give the prognostic index for each patient. As the prognostic index increased from 3 to 9, there was a progressive increase in the hazard ratios and a corresponding deterioration in survival. The patients were then categorized into three prognostic groups based on the hazard ratios for disease specific survival. The differences in the survival curves were highly statistically significant (P < .0001). CONCLUSIONS: Tumor size, histologic grade, and time to local recurrence are the primary determinants of distant metastases and survival in locally recurrent extremity soft tissue sarcomas. The impact of local recurrence on survival varies considerably. The nature of the local recurrence, rather than its presence per se, is a more useful guide to prognosis. We propose a simple staging system based on size, grade, and time to recurrence that correlates extremely well with prognosis and may serve as a guide to make therapeutic decisions in patients with locally recurrent extremity soft tissue sarcomas.

Adolescent↗
PubMed2003

High-grade extremity soft tissue sarcomas: factors predictive of local recurrence and its effect on morbidity and mortality.

OBJECTIVE: To identify patient characteristics associated with the development of local recurrence and the effect of local recurrence on subsequent morbidity and mortality in patients with intermediate- to high-grade extremity soft tissue sarcomas. SUMMARY BACKGROUND DATA: Numerous studies on extremity soft tissue sarcomas have consistently shown that presentation with locally recurrent disease is associated with the development of subsequent local recurrences and that large tumor size and high histologic grade are significant factors associated with decreased survival. However, the effect of local recurrence on patient survival remains unclear. METHODS: From 1975 to 1997, 753 patients with intermediate- to high-grade extremity soft tissue sarcomas were treated at UCLA. Treatment outcomes and patient characteristics were analyzed to identify factors associated with both local recurrence and survival. RESULTS: Patients with locally recurrent disease were at a significantly increased risk of developing a subsequent local recurrence. Local recurrence was a morbid event requiring amputation in 38% of the cases. The development of a local recurrence was the most significant factor associated with decreased survival. Once a patient developed a local recurrence, he or she was about three times more likely to die of disease compared to similar patients who had not developed a local recurrence. CONCLUSIONS: Local recurrence in patients with intermediate- to high-grade extremity soft tissue sarcomas is associated with the development of subsequent local recurrences, a morbid event decreasing functional outcomes and the most significant factor associated with decreased survival. Although 85% to 90% of patients with high-grade extremity soft tissue sarcomas are treatable with a limb salvage approach, patients who develop a local recurrence need aggressive treatment and should be considered for trials of adjuvant systemic therapy.

Amputation, Surgical↗
PubMed2005

Prognostic factors for survival in patients with locally recurrent extremity soft tissue sarcomas.

BACKGROUND: Factors prognostic for survival in patients with locally recurrent extremity soft tissue sarcomas (STS) are poorly defined, thus making it difficult to identify high-risk patients who may benefit from adjuvant therapy. METHODS: A total of 1421 patients underwent surgical treatment for primary extremity STS at a single institution between 1982 and 2002. Of these, 179 (13%) patients underwent complete surgical resection of an isolated local recurrence and were the subjects of this study. Clinicopathologic factors from both the primary tumor and the local recurrence were analyzed. RESULTS: The median interval to initial local recurrence was 16 months: 65% developed a local recurrence by 2 years and 90% by 4 years. Only four patients who presented with a low-grade primary tumor progressed to a high-grade local recurrence. Independent prognostic factors for disease-specific survival after local recurrence were a high histological grade (hazard ratio, 5.1; P = .0004), a large local recurrence tumor size (hazard ratio, 1.5; P = .0001), and a short local recurrence-free interval (hazard ratio, 1.6; P = .0001). Patients who developed a local recurrence >5 cm in < or =16 months (n = 44; 0 low grade) had a 4-year disease-specific survival of 18%, compared with 81% for patients who developed a local recurrence < or =5 cm in >16 months (n = 46; 11 low grade). CONCLUSIONS: Histological grade, local recurrence size, and local recurrence-free interval are independently predictive of survival in patients with locally recurrent extremity STS. A large local recurrence that develops in a short interval indicates a biologically aggressive tumor with a high tumor-specific mortality. Patients who develop such recurrences are ideal subjects for systemic neoadjuvant therapy trials.

Adolescent↗
PubMed2003

Modulation of neural activities by enhanced local selection in the processing of compound stimuli.

The global precedence effect refers to the findings that responses are faster to a global structure than to its local parts and local responses are slowed by incongruent global information. We recorded high-density event-related potentials (ERPs) to study the role of enhanced local selection in the global precedence effect. Hierarchical stimuli were compound letters in which the local letters were either identical (homogeneous stimuli) or the central local letter was brighter than (bright stimuli) or different in color from the others (red stimuli). Subjects were asked to attend to the pop-out local letter of the red and bright stimuli during the local task whereas there was no such instruction for the homogeneous stimuli. Top-down attention to the pop-out local item weakened the global reaction time advantage and the interference effect. The enhanced local selection decreased the amplitude of an occipito-temporal negativity between 240-360 msec but increased the amplitude of a frontal-central negativity between 260-320 msec related to local processing. The incongruency between global and local letters enlarged the posterior N2 in the local condition and this effect was eliminated by enhanced local selection. These effects were evident regardless of whether the pop-out local letter was defined by color or luminance difference. The results support the proposal that distinct neural mechanisms over the posterior and anterior areas are engaged in the selection process that contributes to local processing of compound stimuli.

Adult↗
PubMed1998

A highly conserved RNA-binding protein for cytoplasmic mRNA localization in vertebrates.

BACKGROUND: Cytoplasmic mRNA localization is a widespread mechanism for restricting the translation of specific mRNAs to distinct regions of eucaryotic cells. This process involves specific interactions between cellular factors and localization signals in the 3' untranslated regions of the localized mRNA. Because only a few of these cellular factors have been identified, it is not known whether common factors are utilized for the localization of different mRNAs. We recently discovered Vera, a protein that binds specifically to the Vg1 localization element and is involved in the localization of Vg1 mRNA in Xenopus oocytes. RESULTS: To characterize further the role of Vera in the localization of Vg1 mRNA, we have purified the Vera protein and cloned its gene. Vera is homologous to chicken zip-code-binding protein (ZBP), which binds to a short RNA sequence required for localization of beta-actin mRNA in chick embryo fibroblasts. The predicted amino-acid sequences of Vera and ZBP contain five RNA-binding domains and putative signals for nuclear localization and export. Like the binding of ZBP to beta-actin mRNA, Vera specifically binds to a repeated sequence motif in the Vg1 localization element that is required for Vg1 mRNA localization in Xenopus oocytes. CONCLUSIONS: Vera, a highly conserved component of the mRNA localization machinery, participates in localizing different mRNAs in different cell types. Thus, Vera appears to be a general factor for mRNA localization, and additional factors may be required to specify diverse patterns of RNA localization.

Amino Acid Sequence↗
PubMed1985

Management of locally advanced and inflammatory carcinoma of the breast.

From the data presented, there seems little doubt that multimodality systemic and local therapy offers the best chance of long term control and survival in patients with locally advanced noninflammatory and inflammatory carcinoma of the breast. However, the best method of sequencing these modalities remains inadequately defined. The rationale for systemic therapy is that systemic micrometastases are present at diagnosis; since almost all patients die from systemic disease, it would seem preferable to use chemotherapy first, while the disseminated tumor burden is low. Furthermore, this would allow an assessment of local response to the agents administered. However, chemotherapy almost never sterilizes bulky local disease, and local control rates are significantly improved by concurrent or sequential use of a local modality. From the information presented, it would appear that combined operation and radiotherapy may give a better outcome than either modality alone. However, in series in which chemotherapy plus one local modality are used, the five year, local failure rates were 20 to 35 per cent; with the use of two local modalities, the local failure rate was not significantly better (16, 20 and 22 per cent). The full effect of using two local modalities with systemic chemotherapy has not been satisfactorily explored to date. Many groups have suggested that the local control rate is proportional to the dose of radiotherapy given. Since iridium192 implantation permits larger doses of radiotherapy to the local tumor without an apparent increase in toxicity, it holds great promise as a means of improving local control in this disease and should be considered in all instances. Randomized studies comparing iridium192 with operation as an adjunct to external beam radiotherapy are needed. Although there is little doubt that combination systemic chemotherapy is mandatory for improved survival in these patients, the appropriate drugs, combination and scheduling are yet to be defined. Data from studies of metastatic carcinoma of the breast indicate that combinations of two to four drugs, including doxorubicin, give the best response rates. Recently, a number of anthracycline analogues have been studied, in particular mitoxantrone, with response rates comparable to doxorubicin but with less toxicity. These agents could be used effectively in future chemotherapy programs for locally advanced and inflammatory carcinoma of the breast. The place of endocrine manipulation also remains undefined. In general, women who present with carcinoma of the breast later in life are more likely to have hormone receptor positive, endocrine responsive tumors.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Agents↗
PubMed1997

Local recurrence in breast cancer: implications for systemic disease.

BACKGROUND: Recurrence in breast carcinoma follows a pattern of growth marked by local, regional, or widespread dissemination. Local recurrence may be the harbinger of systemic disease or failure of local control. Delineation of these processes may have implications in treatment. METHODS: A retrospective review found 1,171 patients with stages I and II breast cancer from 1978 to 1990 treated at the City of Hope Medical Center. RESULTS: Twenty-seven percent (n = 313) of patients developed recurrences. These were classified as local, including chest wall and regional nodes (n = 40), local and distant (n = 63), and distant (n = 210). Mean follow-up was 60 months. Multivariate analysis demonstrates tumor size was not different between the three groups, but the presence of positive lymph nodes was: local = 51%, local and distant = 78%, and distant = 64%. The disease-free interval was longest in the local group (42 months) versus the local and distant group (23 months) and distant group (39 months). Median survival was calculated from the time of recurrence: local = 90 months, local and distant = 26 months, and distant = 16 months. CONCLUSIONS: A group of patients with local recurrence have improved survival and do not develop distant disease. This group may benefit from aggressive surgical treatment to control local disease. These data suggest that a subset of breast tumors can act locally aggressive without metastatic potential.

Breast Neoplasms↗
PubMed2002

Factors affecting local recurrence of colonic adenocarcinoma.

PURPOSE: The aim of this retrospective study was to determine which aspects of tumor morphology and histology influenced the incidence of local recurrence after curative resection of colonic adenocarcinoma. METHODS: Patients who had a curative resection for a primary colonic adenocarcinoma between 1980 and 1993 (inclusive) were identified from the colorectal cancer database in the Department of Colorectal Surgery. The charts of patients diagnosed with a local recurrence were then reviewed and their findings at operation and histologic assessment analyzed. Patients were followed up for at least five years or until death. RESULTS: Over the period of study, 1,031 patients had a curative resection for colonic adenocarcinoma. Local recurrences were detected in 32 patients (3.1 percent). The gender distribution of patients with local recurrence was 18 males (56.3 percent) and 14 females (43.7 percent) with a mean age of 63.4 years. The median time to local recurrence was 13 (range, 2-71) months. The distribution of primary tumors that recurred locally favored the cecum (n = 9; 28.1 percent) and sigmoid colon (n = 14; 43.7 percent) over other locations; these were, however, the most common sites of primary lesions. Less common sites included the ascending colon (n = 0; 0 percent), hepatic flexure (n = 2; 6.3 percent), transverse colon (n = 1; 3.1 percent), splenic flexure (n = 3; 9.4 percent), and descending colon (n = 3; 9.4 percent). Of the total number of tumors, 101 were found to be adherent to at least 1 other intra-abdominal viscus, and 12 (11.9 percent) recurred locally. Other factors associated with local recurrence were tumor perforation and fistulation. Overall, 30 tumors (2.9 percent) were perforated, and 6 (20 percent) recurred locally. Four tumors (0.4 percent) were fistulating; of these, 2 (50 percent) recurred locally. Advanced tumor stage was also associated with an increased rate of local recurrence (Stage I, 0 percent; Stage II, 2.05 percent; Stage III, 7.0 percent; and Stage IV, 6.1 percent). Similarly, tumor differentiation was related to local recurrence, with no instances in well-differentiated tumors, 2.8 percent in moderately differentiated tumors, and 6.8 percent in poorly differentiated tumors. CONCLUSIONS: The location of the primary tumor is not a factor in producing local recurrence. Fixity to another viscus, perforation or fistulation, advanced stage of disease, and differentiation of tumor appear to increase the chances of recurrence of curatively resected colonic carcinoma. Although the recurrence rate is higher in these groups than for tumors overall, definitive oncologic surgery prevents recurrence in the majority of cases. No colonic tumor that was T1 or T2 (N0, N1, or N2) or that was well differentiated recurred locally.

Adenocarcinoma↗
PubMed1997

Radiation therapy for rhabdomyosarcoma: local failure risk for Clinical Group III patients on Intergroup Rhabdomyosarcoma Study II.

PURPOSE: A subset of 362 pediatric patients with rhabdomyosarcoma was selected from a total of 532 eligible IRS-II patients in Clinical Group III to assess the local and regional failure rates following radiotherapy and to determine patient, tumor, and treatment factors contributing to the risk for local and regional failure. METHODS AND MATERIALS: The study population was selected from all eligible IRS-II Clinical Group III patients. Excluded patients were those with "special pelvic" primary sites whose protocol management restricted radiotherapy (n = 123), and those who were removed from the study before radiotherapy was to begin, or because it was omitted (n = 47). A binary recursive partitioning model was used to identify subgroups of the remaining 362 patients at risk of local or regional failure. RESULTS: The local (only) failure rate was 17% (95% confidence interval, 13-21%), and the local (all) failure rate was 20% (95% confidence interval, 16-24%). The 5-year actuarial risk of local (all) failure was 22% (95% confidence interval, 18-27%). The risk of regional (nodal) failure was between 2% and 23%. Increasing tumor size predicted an increased local failure risk. Primary tumors located above the clavicle had a reduced risk of local failure. The binary recursive partitioning model identified a subset of patients at high risk of local failure. Those patients had primary tumors in the chest, pelvic region, extremity, or trunk, or tumors > 10 cm in diameter. Their local failure rate was 35% (compared to 15% for the remaining patients). The subset of patients at high risk for regional (nodal) failure had node involvement at diagnosis and a primary tumor originating at a site other than orbit, parameningeal, or trunk. Compliance with radiation treatment guidelines approached but did not achieve statistical significance as a predictive factor for local failure. By univariate analysis, factors not influencing local failure risk were age, race, gender, adenopathy, and histology. CONCLUSION: Radiation therapy and chemotherapy administered to Clinical Group III patients entered into the IRS-II protocol produced sustained local control in most cases. Knowledge of the factors which predict an increased risk of local or regional failure will facilitate the design of new treatment strategies.

Adult↗
PubMed1995

[Local recurrence following breast-conserving treatment for breast carcinoma; treatment and prognosis in 82 patients].

OBJECTIVE: To evaluate the treatment and prognosis of 82 patients with local relapse in the breast as the first event after breast-conserving therapy of operable breast cancer. DESIGN: Descriptive and retrospective. SETTING: 17 general hospitals in southeast North-Brabant and North-Limburg. METHODS: Using the registries of the Comprehensive Cancer Centre South in Eindhoven (1981-1990) and the Bernard Verbeeten Institute in Tilburg (1981-1987), 82 patients were identified who had developed local recurrence after breast-conserving therapy. RESULTS: The mean age of the 82 patients at the time of detection of local recurrence was 51 years. 46 recurrences (56%) were localized at or near the site of the original tumour, 14 (17%) were detected elsewhere in the breast, 15 (18%) showed diffuse spread through the breast and seven (9%) were completely or partly localized in the skin. Nine recurrences (11%) were non-invasive. Of the 82 patients four received adjuvant systemic therapy only and no surgery. Of the 78 patients treated with surgery 72 underwent mastectomy, 6 local excision. After treatment, the actuarial five-year overall survival, distant recurrence-free survival and disease-free survival rates were 60%, 43% and 31% respectively. Local control, defined as survival without second local recurrence and without local progression of the disease, was 57% after five years. CONCLUSION: The five-year distant recurrence-free and disease-free survival rates for patients with local recurrence after breast conserving-therapy were low. The high proportion of second local recurrences and local progression of disease in this study underlines the difficulty of obtaining local control after treatment of local recurrence.

Adult↗
PubMed1991

Developmental changes in finger localization.

This experiment examined the basis for developmental changes in finger localization performance. Groups of children aged 6, 8 and 10 years were tested on an uncrossed localization task and a crossed localization task or a model localization task. In the uncrossed localization task they used the stimulated hand to localize the stimulated fingers on the stimulated hand. In the crossed localization task they used the unstimulated hand to localize the stimulated fingers on the unstimulated hand. In the model localization task they used the stimulated hand to localize the stimulated fingers on a model hand. Localization for the uncrossed task was more accurate than for either the crossed or model tasks, but developmental differences in localization accuracy were comparable for each of the three localization tasks. The present results do not support the suggestion (Galin et al., Brain Lang. 4, 588-590, 1977; Quinn and Geffen, Neuropsychologia 24, 793-804, 1986) that developmental changes in crossed localization result from changes in the efficiency of interhemispheric transfer of information.

Analysis of Variance↗
PubMed1990

Maintenance of local cerebral blood flow after acute neuronal death: possible role of non-neuronal cells.

In brain, a major factor regulating local perfusion is local neuronal activity. However, we have recently discovered that, in rat, five days after selective neuronal destruction in the parietal cortex by local microinjections of the excitotoxin ibotenic acid, local cerebral blood flow, within the lesion, remains in the normal range. We studied whether proliferating non-neuronal cells and/or local changes in microvascular density participate to maintain local cerebral blood flow. Rats were anesthetized (halothane 1-3%), ibotenic acid (10 micrograms in 1 microliter) was locally microinjected in a restricted region of the parietal cortex, and animals were allowed to recover. Three, five, seven, 11, 30 days later local cerebral blood flow was measured autoradiographically under chloralose anesthesia (40 mg/kg, s.c.) by the [14C]iodoantipyrine technique. Cellular density or microvascular area were determined on sections stained with Thionine or processed for the endothelial marker alkaline phosphatase, respectively. Local neurons were destroyed by 24 h after microinjections of ibotenic acid. However, from three to 11 days after lesion local cerebral blood flow was unchanged (P greater than 0.05; n = 5), thereafter declining so that by 30 days blood flow was 48 +/- 6% of control (P less than 0.05; n = 5). Cellular density increased within the lesion by 17.5-fold at seven to 11 days (P less than 0.01) and declined to a 11.7-fold elevation above control at day 30 (P less than 0.01). New cells consisted of macrophages, endothelium and glial fibrillary acidic protein-positive astrocytes. The microvascular area increased 4.2-fold from three to 11 days (P less than 0.01). The patency of the presumably newly formed vessels was determined by the presence of intravascular red blood cells, which were revealed histochemically. The area occupied by red blood cells within cerebral microvessels, in contrast to microvascular area, did not increase until seven days after lesion, reaching a 3.2-fold increase at 11 days. Thus within the lesion, local cerebral blood flow remains constant during the phase in which cellular and microvascular density increases. The presumably newly formed vessels cannot contribute to maintain local cerebral blood flow since during this phase they are not patent; rather patency develops coincident with the decline in local cerebral blood flow. We conclude that non-neuronal cells, most likely activated macrophages, may be an important factor regulating local cerebral perfusion, after acute neuronal death.

Alkaline Phosphatase↗
PubMed2003

Metapopulation dynamics with quasi-local competition.

Stepping-stone models for the ecological dynamics of metapopulations are often used to address general questions about the effects of spatial structure on the nature and complexity of population fluctuations. Such models describe an ensemble of local and spatially isolated habitat patches that are connected through dispersal. Reproduction and hence the dynamics in a given local population depend on the density of that local population, and a fraction of every local population disperses to neighboring patches. In such models, interesting dynamic phenomena, e.g. the persistence of locally unstable predator-prey interactions, are only observed if the local dynamics in an isolated patch exhibit non-equilibrium behavior. Therefore, the scope of these models is limited. Here we extend these models by making the biologically plausible assumption that reproductive success in a given local habitat not only depends on the density of the local population living in that habitat, but also on the densities of neighboring local populations. This would occur if competition for resources occurs between neighboring populations, e.g. due to foraging in neighboring habitats. With this assumption of quasi-local competition the dynamics of the model change completely. The main difference is that even if the dynamics of the local populations have a stable equilibrium in isolation, the spatially uniform equilibrium in which all local populations are at their carrying capacity becomes unstable if the strength of quasi-local competition reaches a critical level, which can be calculated analytically. In this case the metapopulation reaches a new stable state, which is, however, not spatially uniform anymore and instead results in an irregular spatial pattern of local population abundance. For large metapopulations, a huge number of different, spatially non-uniform equilibrium states coexist as attractors of the metapopulation dynamics, so that the final state of the system depends critically on the initial conditions. The existence of a large number of attractors has important consequences when environmental noise is introduced into the model. Then the metapopulation performs a random walk in the space of all attractors. This leads to large and complicated population fluctuations whose power spectrum obeys a red-shifted power law. Our theory reiterates the potential importance of spatial structure for ecological processes and proposes new mechanisms for the emergence of non-uniform spatial patterns of abundance and for the persistence of complicated temporal population fluctuations.

Competitive Behavior↗