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Overexpression of Bcl-XL by cytotoxic drug exposure confers resistance to ionizing radiation-induced internucleosomal DNA fragmentation.

Acquired resistance to diverse chemotherapeutic agents has been associated with overexpression of the P-glycoprotein. We have selected human U-937 cells for clones resistant to the cytotoxic agents doxorubicin (U-A20) and vincristine (U-V20). The results demonstrate that P-glycoprotein-positive U-A20 and U-V20 cells exhibit resistance to inducers of internucleosomal DNA fragmentation. Although parental U-937 cells responded to ionizing radiation with the DNA laddering characteristic of physiological cell death, the drug-resistant lines were insensitive to this effect. The U-A20 and U-V20 clones were also resistant to endonucleolytic DNA cleavage associated with exposure to tumor necrosis factor or ceramide. Previous work has demonstrated that physiological cell death is inhibited by overexpression of the Bcl-2 protein. However, analysis of Bcl-2 revealed similar levels in the parental and drug-resistant cells. In contrast, we show that U-A20 and U-V20 cells overexpress the Bcl-2-related protein, Bcl-xL. Moreover, studies with a U-937 cell line transfected with a Bcl-XL expression vector confirm resistance to ionizing radiation-induced DNA fragmentation and cell killing. These findings suggest that, unlike Bcl-2, Bcl-XL may be constitutively overexpressed as a result of selection for cytotoxic drug resistance and that Bcl-XL participates in an acquired form of multimodality resistance to chemotherapeutic agents and radiation.

Base Sequence↗

Multimodality stereotactic brain tissue identification: the NASA smart probe project.

Real-time tissue identification can benefit procedures such as stereotactic brain biopsy, functional neurosurgery and brain tumor excision. Optical scattering spectroscopy has been shown to be effective at discriminating cancer from noncancerous conditions in the colon, bladder and breast. The NASA Smart Probe extends the concept of 'optical biopsy' by using neural network techniques to combine the output from 3 microsensors contained within a cannula 2. 7 mm in diameter (i.e. the diameter of a stereotactic brain biopsy needle). Experimental data from 5 rats show the clear differentiation between tissues such as brain, nerve, fat, artery and muscle that can be achieved with optical scattering spectroscopy alone. These data and previous findings with other modalities such as (1) analysis of the image from a fiberoptic neuroendoscope and (2) the output from a microstrain gauge suggest the Smart Probe multiple microsensor technique shows promise for real-time tissue identification in neurosurgical procedures.

Brain↗

fMRI-constrained MEG source imaging and consideration of fMRI invisible sources.

Recent studies on multimodal brain source imaging have shown that the use of functional MRI (fMRI) prior information could enhance spatial resolution of magnetoencephalography (MEG), while MEG could compensate poor temporal resolution of fMRI. This article deals with a multimodal imaging method, which combines fMRI and MEG for enhancing both spatial and temporal resolutions. Recent studies on the combination of fMRI and MEG have suggested that the fMRI prior information could be very easily implemented by just giving different weighting factors to the diagonal terms of source covariance matrix in linear inverse operator. We applied the fMRI constrained imaging method to several simulation data and experimental data (Japanese language lexical judgment experiment), and found that some MEG sources may be eliminated by the introduction of the fMRI weighting and the eliminated sources may affect source estimation in fMRI activation regions. In this article, in order to check whether the eliminated sources were fMRI invisible ones or just spurious ones, we placed small numbers of regional sources (rotating dipoles) around all possible activation regions and investigated their temporal changes. By investigating the results carefully, we could evaluate whether the missed sources were real or not.

Algorithms↗

Colorectal cancer.

OBJECTIVES: To provide a review of the etiology, risk factors, treatment, and nursing care of patients with colorectal cancer. DATA SOURCES: Review articles, screening guidelines, and textbook chapters. CONCLUSIONS: Although colorectal cancer remains a major health threat in the United States, advances made over the last 10 years in prevention, diagnosis, and treatment have changed the management and care of patients with this disease. The key to survival of colorectal cancer is screening and early detection. IMPLICATIONS FOR NURSING PRACTICE: Regardless of the multimodalities of treatment used, the nurse's role as educator, caregiver, supporter, and advocate requires an ongoing commitment to remain knowledgeable of and current in advances made in the prevention, detection, and treatment of colorectal cancer.

Adult↗

Prognostic factors and treatment-related changes associated with return to work in the multimodal treatment of chronic back pain.

The goals of the current study were to determine those preprogram (= prognostic) variables and treatment-related changes that predict return to work in the multimodal management of chronic back pain. The outcome measures for 143 patients at 6-month follow-up were analyzed. The program had a duration of 4 weeks, was based largely on the functional restoration approach (Mayer and Gatchel, 1998), and occurred within a workers' compensation framework. Some 87% of the patients successfully returned to work. Three sets of predictor variables were considered: demographic/socioeconomic data, physical measures, and psychological measures. Three prognostic variables proved to be significant negative predictors of return to work: time off work, previous spinal surgery, and a clinically elevated (preprogram) score on the MMPI-2 scale Lassitude-Malaise (Hy3). A repeated-measures MANOVA showed an incomplete return to work to be associated with only limited improvement in self-reported disability and pain report. However, patients who failed to return to work did not differ with regard to improvement in objective physical functioning or psychological distress. It is therefore hypothesized that a change in the perceived disability status is the key element necessary to return patients with chronic back pain to work, although ongoing reinforcement schemes operative in the home/work environment may lead to a relapse in the posttreatment phase.

Adult↗

Does aliphatic chain length influence carbocyanines' orientation in supported lipid multilayers?

UV-Vis linear dichroism was used to study the orientation of 3,3'-dihexyloxacarbocyanine (DiOC6(3)) and 3,3'-dihexadecyloxacarbocyanine (DiOC16(3)) in supported multilayers of dipalmitoylphosphatidylcholine (DPPC) and dilauroylphosphatidylcholine (DLPC). Orientational probability density functions were similar for the two carbocyanines in both lipids. Multimodal distributions were found in all cases. The main peak is at 9 degrees-11 degrees relative to the bilayer normal axis, except for DiOC16(3) in DLPC multilayers (main peaks at 13 degrees and 90 degrees). Quenching studies revealed that the two carbocyanines are localized at the interface region of the membrane regardless of the lipid matrix they are inserted in. Combining these data with linear dichroism results lead to the conclusion that both the aliphatic chain length of carbocyanines and the lipid phase have little influence in the structural organization of these probes in lipidic bilayers. The partition constants of DiOC6 (3), K(p), were determined from fluorescence anisotropy measurements; the values obtained were K(p) (DPPC) = (2.39 +/- 0.05) x 10(3) and K(p) (DLPC) = (5.01 +/- 1.15) x 10(3).

1,2-Dipalmitoylphosphatidylcholine↗

[Development of guidelines for rehabilitation of patients with stroke: analysis of therapeutic procedures].

The Federal Insurance Institute for Salaried Employees (BfA, Bundesversicherungsanstalt für Angestellte) in Berlin took the initiative to develop evidence-based guidelines for rehabilitation including stroke rehabilitation. In the present study we performed a systematic survey of the scientific literature on stroke rehabilitation and deduced 8 evidence-based therapeutic modules. They were supplemented by 5 practice-based modules to cover the full range of interventions currently applied in stroke rehabilitation. Modules are clusters of various interventions which were aggregated according to the rehabilitative goal they have in common. Data were analysed from 8,876 BfA patients, the total population of "neuro"-patients in 2001 and 2002 with 142,951 interventions and 1,071,885 appointments. Stroke diagnoses covered ICD-10 codes I60, I61, I62, I63, I64 or were coded by G45, G81 and one of these I-codes. Stroke rehabilitation as provided in daily practice was found to be a complex multimodal treatment programme in all hospitals which were studied. On average, patients receive treatments from 7.3 therapeutic modules. A dominating role is played by "motor modules". Obviously, they play a major role in acute stroke rehabilitation in all hospitals compared to cognitive retraining, language therapy and especially improvement of psychic functions, which were significantly less applied. A dramatic variation could be shown to exist between the rehabilitation hospitals (1) with respect to the number of patients who were treated with a given module (e. g., some modules showed variations between 18 % and 100 %), and (2) with respect to treatment intensity and treatment duration per week. Several factors can be taken into account for interpretation of this high variance. Intrinsically, the high variation in symptomatology after stroke can play a major role, as both the deficit profile and the level of severity of a given deficit and the combined severity level can vary from patient to patient. On the other hand, extrinsic factors such as lack of staff may also account for some of the differences. In any case, the results show the necessity to optimize stroke rehabilitation by development and implementation of guidelines. Yet, they also point to a need for further research into rehabilitation interventions and procedures to yield evidence for the approximately 30 % of "only" practice-based interventions.

Adult↗

Clean intermittent catheterization in genitally sensate children: patient experience and health related quality of life.

PURPOSE: Clean intermittent catheterization (CIC) has proven successful for bladder emptying in children without genital sensation with success rates of 94% to 100% in select groups. A subset of the pediatric population requires CIC for bladder dysfunction, yet has normal genital sensation. This study was designed to assess our experience with CIC in genitally sensate children and the health related (HR) quality of life (QOL) for them and their families. MATERIALS AND METHODS: A multimodality questionnaire on the usage, learning curve and degree of difficulty of CIC was developed. The PedsQLtrade mark 4.0 Generic Core Scales, a reliable, validated HRQOL survey developed for pediatric patients with chronic disease, was used to assess patient and parental QOL. Children in our practice with normal genital sensation and bladder dysfunction requiring CIC were contacted to complete these questionnaires. When possible, QOL data were collected from the patient (self-report) and one or both of the parents (parent-proxy report). RESULTS: Data for 12 males and 8 females were collected, including 30 QOL questionnaires (12 self, 18 proxy). Of the patients 80% were able to learn CIC technique in 1 clinic visit with the help of a nurse. On a 10-point scale (1-not difficult, 10-very difficult) the mean degree of difficulty for learning the CIC technique was 3.25 for males and 4.00 for females (3.55 overall). On a 10-point scale (1-uncomfortable, 10-very comfortable) mean comfort level with the CIC technique was 9.12 for females and 9.46 for males (9.33 overall). On the PedsQL 100-point scale mean QOL was 83.24 for the self-report compared to 81.78 for the parent proxy report. The QOL for normal children has previously been shown as 83 (self) to 87.61 (proxy). CONCLUSIONS: CIC was an easy technique for most sensate children to learn in 1 visit and master in a short time. Overall comfort with the technique was excellent and few problems were encountered. Their HRQOL was comparable to that of normal children.

Adolescent↗

The context of risky behaviors for Latino youth.

BACKGROUND AND SIGNIFICANCE: Alarming numbers of Latino teens continue to engage in behaviors that place them at risk for pregnancy and sexually transmitted infections including HIV. DESIGN: This study includes data from six focus groups with 38 Latinas. The primary purpose of the focus groups was to elicit antecedents to unsafe sex to guide the development of an HIV-prevention intervention for adult Latinas. The data were reanalyzed using the rich content that had been elicited about community teens. FINDINGS: Six major themes were identified surrounding teen issues and concerns. These are (a) the culture of risky behaviors; (b) romance: illusion and reality; (c) parental involvement: a protective factor; (d) HIV: knowledge versus ignorance; (e) HIV among youth: fear, stigma, and anger; and (f) saving our youth. IMPLICATIONS: A multimodal approach is required to help teens adopt healthy life styles, remain in school, and have a positive relationship with their parents.

Adolescent↗

The mellow years?: neural basis of improving emotional stability over age.

Contrary to the pervasive negative stereotypes of human aging, emotional functions may improve with advancing age. However, the brain mechanisms underlying changes in emotional function over age remain unknown. Here, we demonstrate that emotional stability improves linearly over seven decades (12-79 years) of the human lifespan. We used both functional magnetic resonance imaging and event-related potential recording to examine the neural basis of this improvement. With these multimodal techniques, we show that better stability is predicted by a shift toward greater medial prefrontal control over negative emotional input associated with increased activity later in the processing sequence (beyond 200 ms after stimulus) and less control over positive input, related to a decrease in early activity (within 150 ms). This shift was independent from gray matter loss, indexed by structural magnetic resonance data. We propose an integrative model in which accumulated life experience and the motivation for meaning over acquisition in older age contribute to plasticity of medial prefrontal systems, achieving a greater selective control over emotional functions.

Adolescent↗

Medical-behavioral treatment of the older alcoholic patient.

The purpose of the present research was to assess the treatment effectiveness of a multimodality alcoholism treatment program with older alcoholic patients. Treatment success was defined as 1 year of sobriety following inpatient treatment in a multicomponent program oriented around aversion conditioning to alcohol. A total of 87 patients, 65 years or older, were admitted, and a total of 78 patients were treated in the Raleigh Hills Hospital-Portland over a 2-year period. Descriptive psychological test data, demographic characteristics, and symptom history data were obtained for these patients and related to treatment outcome. This population of elderly alcoholic patients treated as successfully as younger patients. Their abstinence percentage combined for the two treatment years was 65.4% continuous sobriety over a 12-month follow-up period.

Age Factors↗

[Radical surgery for removing a malignant tumor of the temporal bone with extra- and intracranial involvement].

The paper presents a clinical case of combined therapy for adenocystic carcinoma of the petrous pyramid. The basic stages of treatment were preoperative radiation, tumor block resection, and postoperative radiation therapy. Based on the discussion of data available in the literature and on the case presented, practical guidelines for treatment policy are given. Such basic guidelines are as follows:--a lingering drug-unresponsible inflammatory process may be a manifestation of cancer diseases;--if there are clinical and diagnostic signs of neoformation, biopsy of a tumor (tissue under suspicion) is the basic premedical measure;--treatment policy combines different methods of multimodality treatment, but if there is an epithelial tumor, treatment should be started with radio- and/or chemotherapy.

Adenocarcinoma↗

Chemoradiotherapy for esophageal cancer: current status and perspectives.

The optimal role of chemoradiotherapy in the multimodality treatment of esophageal cancer is still controversial. According to a series of clinical trials, definitive chemoradiotherapy is considered the standard of care for patients with medically inoperable or surgically unresectable esophageal cancer. This modality provides survivals comparable to those in Western series of surgery alone and is one of the standards of care even for resectable-stage disease. Recent reports of primary chemoradiotherapy from Japan suggest survival comparable to that of surgery in Japanese patients with stage I disease, but radical surgery is still the standard treatment for T2-3NanyM0 disease in Japan. However, it is clear that this approach has limitations in treatment outcomes. Trimodality therapy, i.e., preoperative chemoradiotherapy followed by surgery, is more favored than surgery alone in clinical practice, particularly in patients with adenocarcinoma, although current data from randomized trials are insufficient to support this approach. To improve the local control rate of chemoradiotherapy, intensification of the radiation dose has been attempted, but this has failed to demonstrate any superiority in terms of local control or survival. The addition of new agents, including molecular targeting agents, to the current standard chemoradiotherapy has shown more promising results and warrants further investigations in future studies. Salvage treatment for patients who do not achieve a complete response (CR) is necessary to improve the overall treatment results. Salvage surgery, as well as endoscopic resection, in selected patients, may provide an improvement in survival. Until high rates of local control can be consistently achieved with chemoradiotherapy alone, these salvage treatments will be an integral component of multimodality treatment for esophageal cancer, and should be active areas for clinical investigations.

Antineoplastic Combined Chemotherapy Protocols↗

Multimodal electroneurophysiological studies of systemic lupus erythematosus.

The purpose of this study was to obtain electrophysiological documentation of possible involvement of central and peripheral nervous system (CNS and PNS) in systemic lupus erythematosus (SLE) patients even in the absence of neurological manifestations. The study included 30 consecutive patients with SLE and 25 age- and sex-matched volunteers as a control group. They were subjected to neurological and rheumatological tests and an extensive battery of neurophysiological tests, besides Wechsler adult intelligence scale. Overt neurological manifestations were observed in 14 patients (46.7%). Neurophysiological data revealed that 25 patients (83%) had at least 2 abnormal tests; 11 (68.8%) patients of the asymptomatic group and 14 patients (100%) of the symptomatic group with no significant differences between them. Seventeen patients (56.7%) had evidence of PNS dysfunction either in nerves (46.7%) or muscles (10%); 7 of them in the asymptomatic group. Twenty-four patients (80%) had evidence of CNS dysfunction. Twenty-two patients (73%) had abnormalities recorded on electroencephalography; 9 patients in the asymptomatic group and 13 patients in the symptomatic group. Eleven patients (37%) had abnormal values of P100 of visual evoked potential; 5 patients in the asymptomatic group and 6 in the symptomatic group. Eight patients (26.7%) had abnormal latency of wave I of brain stem response; 3 of them in the asymptomatic group. Abnormal prolongation of the P300 component of event-related potentials was recorded in 2 patients (12.5%) of the asymptomatic group, while low IQ was observed in 8 patients of each group. Neurophysiological abnormalities are fairly common in SLE patients whether symptomatic or asymptomatic. The use of such tests favors a true incidence of nervous system involvement, more accurate diagnosis, and may lead to better clinical care before the development of debilitating CNS and PNS changes.

Adolescent↗

Event-related potentials recorded from the cingulate gyrus during attentional tasks: a study in patients with implanted electrodes.

Recent neuroimaging data suggests that the cingulate gyrus is involved in a variety of cognitive tasks. In this study sensory field potentials were directly recorded from the cingulate gyrus in order to investigate its implication in attentional processes associated or not with a motor task. Evoked potentials recordings were performed in 29 epileptic patients with multilead electrodes implanted for presurgical evaluation, who agreed to participate in an experimental protocol consisting of a series of paradigms designed using a warning auditory tone, two distinct visual patterns and various attentional, memory, motor and decisional tasks. Our data shows that evoked potentials could be recorded from various parts of the cingulate gyrus. The inclusion of an instruction in the experimental paradigm resulted in an increase in the amplitude of the late, intrinsic component of the visual evoked potential culminating at about 450 ms. Several variations of response patterns across individuals were identified. We conclude that the cingulate gyrus appears to be a multimodal area involved in several types of cognitive activity, including attention. Variations in response patterns are probably related to differences in the strategy adopted by each subject when faced with a particular cognitive task.

Adult↗

Manual therapy for mechanical neck disorders: a systematic review.

Neck disorders are common, disabling and costly. Randomized trials were reviewed using a Cochrane format, to determine if manual therapy improves pain, function and patient satisfaction in adults suffering from neck disorders with and without radicular findings or headache. Sequenced computerized searches ended in December 1997. Two independent reviewers extracted data while three assessed trial quality. Standard mean difference and relative risks were translated to number needed to treat (NNT) and the percent treatment advantage. The 20 selected trials' quality was 2.4 (SD: 1.04) on the 5-point scale described by Jadad. Trials were clinically heterogenous. Manipulation alone, mobilizations alone, manipulation/mobilization and treatments including massage consistently showed similar effects to placebo, wait period or control. Multimodal manual therapy care including exercise were superior to a control, to certain physical medicine methods and to rest for pain and patient satisfaction. The NNT for a clinically important reduction in pain varied from 2 to 11 and treatment advantage from 6% to 41% at the cost of benign transient side-effects. While results remain inconclusive, some clinical themes have emerged. For mechanical neck disorder with or without headache, it appears that to be most beneficial, manual therapies should be done with exercise for improving pain and patient satisfaction. Manipulation and mobilization alone appear to be less effective. Factorial design would help delineate the magnitude of effect for each component of care.

Adult↗

Indications and Role of Liver Transplantation for Malignant Tumors.

PURPOSE: The indication for liver transplantation in malignant liver tumors has been controversial due to disappointing results and shortage of donor organs. The authors evaluated the experience and results of a single center in order to define present indications and selection criteria in hepatobiliary malignancy. PATIENTS AND METHODS: Retrospective analysis of 212 patients who underwent liver transplantation for malignant tumors between 1972 and 1995: Primary hepatobiliary tumors: hepatocellular carcinoma, n = 124 (with underlying cirrhosis, n = 86; fibrolamellar subtype, n = 8); intrahepatic bile duct (cholangiocellular) carcinoma, n = 24; proximal bile duct carcinoma, n = 29; other uncommon entities (n = 15); secondary liver tumors: neuroendocrine, n = 11, and nonendocrine, n = 9. RESULTS: Survival rates in primary liver cancer were correlated to International Union Against Cancer (UICC) tumor stage. For hepatocellular and proximal bile duct carcinoma significantly better outcome was found in UICC-tumor stage I and II versus III and IV. No long-term survival was found after transplantation for intrahepatic bile duct carcinoma, hemangiosarcoma and nonendocrine liver metastases. Comparison of transplant and resected patients with hepatocellular carcinoma stage I and II with underlying cirrhosis showed better survival after transplantation: 1-, 3-, 5-year survival rate of 83.3% versus 76.9%, 75.8% versus 44.0%, 60.6% versus 44.0%, and median survival 96.5 versus 23.2 months. Although this difference was not significant, no patient died from tumor recurrence in the transplant group versus three in the resection group. DISCUSSION AND CONCLUSIONS: Patients with malignant tumors can be selected for transplantation with predictable likelihood for long-term survival. According to the present data, liver transplantation can be considered in unresectable UICC-stage II hepatocellular and proximal bile duct carcinoma, the uncommon entities fibrolamellar carcinoma, epitheliod hemangioendothelioma and hepatoblastoma as well as liver metastases from neuroendocrine tumors. UICC-stage II and IV hepatocellular carcinoma as well as intrahepatic bile duct carcinoma, hemangiosarcoma and metastases from nonendocrine tumors should be excluded from transplantation alone. For hepatocellular carcinoma, multimodality treatment protocols have had a proven impact on the prevention of early recurrence and prolongation of survival. There is evidence that liver transplantation in still resectable hepatocellular carcinoma with underlying cirrhosis might be more appropriate in order to cure the cancer-bearing disease.

Journal Article↗

[Role of multimodal evoked potentials in evaluations of persistent vegetative state of nontraumatic origin].

Persistent vegetative state (PVS) is a kind of release from coma, manifesting by absence of any signs of cognitive activity. Progress in reanimatology leads to an increase in the number of patients with PVS, thus creating a new medical and social problem. Study of atraumatic PVS acquires special importance because of a drastic increase in its incidence, necessitating definition of criteria of this state formation and its prognostic signs. Multimodal evoked potentials (MEP) now play an important role in diagnosis and prediction of PVS. The impact of acoustic stem (ASEP), visual (VEP), somatosensory (SSEP), and cognitive (CEP) evoked potentials is analyzed and early diagnostic and prognostic neurophysiological criteria are defined. Results of dynamic examinations of 23 patients (9 men and 14 women) aged 10-67 years with atraumatic PVS are presented. According to neurophysiological data, PVS in the majority of patients is characterized by absence of cognitive responses to a significant stimulus (wave P300) during examinations of CEP and of cortical response during examination of SSEP. VEP and long latent acoustic evoked potentials are as rule intact in atraumatic PVS. According to ASEP, stem functions were intact or slightly changed in the examined patients with PVS. Prognostically unfavorable and relatively favorable signs in the time course of MEP are defined.

Adolescent↗