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Continuous distributions of specific ventilation recovered from inert gas washout.

We describe a new technique for recovering continuous distributions of ventilation (V) as a function of tidal ventilation/volume ratio (V/V0) from the nitrogen washout. The analysis yields a continuous distribution of V as a function of V/V0 represented as fractional ventilations of 50 compartments plus dead space. The procedure was verified by recovering known distributions from data to which noise had been added. Using an apparatus to control the subject's tidal volume and FRC, mixed expired N2 data gave the following results: a) the distributions of young, normal subjects were narrow and unimodal with a mean ln standard deviation of 0.56 plus or minus 0.13; b) those of subjects over age 40 were broader (ln SD 0.86 plus or minus 0.19) with more poorly ventilated units; c) patients with pulmonary disease of all descriptions showed enlarged dead space; d) patients with cystic fibrosis showed multimodal distributions with the bulk of the ventilation going to overventilated units; and e) patients with obstructive lung diseases fell into several classes, three of which are illustrated. These results suggest that our approach is well suited for clinical investigation.

Adult↗

Results and follow-up of locally advanced cancer of the exocrine pancreas treated with radiochemotherapy.

UNLABELLED: In locally advanced carcinoma of the exocrine pancreas combined radiochemotherapy has been established as a standard treatment. MATERIALS AND METHODS: Two different treatment schemes have been consecutively used. Between 1/1994 and 12/2001, a total of 110 patients with locally advanced adenocarcinoma of the pancreas were treated with hyperfractionated accelerated radiotherapy to a total dose of 44.8 Gy combined with 5-fluorouracil (5-FU) (600 mg/m2) and folinic acid (FA) (300 mg/m2) injection. Chemotherapy was repeated monthly in non-progressive disease. From 1/2002 to 11/2003, in another 15 consecutive patients, chemotherapy was changed to gemcitabine (Gem) (300 mg/m2) and cisplatinum (Cis) (30 mg/m2), followed by gemcitabine (1000 mg/m2) every 2 weeks in non-progressive patients. RESULTS: Median survival in the 5-FU/FA group was 10.3 months with a 1-year survival of 46.6% and a 2-year survival of 20.1%. Median time to progression was 8.6 months. Treatment was well tolerated with nausea/vomiting grade I/II in 58.2%, grade III/IV in 14.5%, diarrhea grade I/II in 27.3%, leucopenia/thrombopenia grade I/II in 21.8%, grade III/IV in 7.2%, and mucositis grade III/IV in 7.2%. In the Gem/Cis group, median survival was 13.8 months with a 1-year survival of 54.9% and a 2-year survival of 24.4%. The toxicity data also revealed comparable feasibility: nausea/vomiting grade I/II in 46.7%, grade III/IV in 20%, diarrhea grade I/II in 20%, leucopenia/thrombopenia grade I/II in 26. 7%, and grade III/IV in 13.3%. CONCLUSION: Radiochemotherapy in locally advanced pancreatic cancer is an effective and well-tolerated treatment. The long-term efficacy concerning survival is limited. The integration of predictive factors and new chemotherapeutic agents like gemcitabine in the multimodality treatment may give a more promising perspective. Because of the narrow therapeutic index of gemcitabine-based radiochemotherapy schemes, a feasible combination of radiotherapy treatment volume and gemcitabine dose must be found.

Adult↗

Trends in the United States for the management of adenocarcinoma of the rectum.

Data from surveys conducted by the Commission on Cancer of the American College of Surgeons were examined to identify recent trends in the treatment of carcinoma of the rectum. Between 1973 and 1978, the stage of disease at diagnosis for the total series changed little, but significant upgrading in the stage of disease at diagnosis for the black patients was observed. There was increasing use of a multimodality approach to treatment combining operation with radiotherapy. The use of chemotherapy alone or in combination with other therapies, while never widely used, declined during the interval observed. Significant changes occurred in the type of operations performed for carcinoma in the upper two-thirds of the rectum. During this interval, abdominoperineal resection was increasingly being displaced by low anterior resection. The trend toward multimodality treatment and the use of effective sphincter preserving procedures represent significant changes noted in this survey in the therapy of carcinoma of the rectum.

Adenocarcinoma↗

Multimodality expression profiling shows SEPT9 to be overexpressed in a wide range of human tumours.

Septins are an evolutionarily conserved family of GTPases with diverse functions including roles in cytokinesis that have been implicated in neoplasia. To address the potential role of SEPT9 in tumorigenesis, we assessed the expression of SEPT9 in 7287 fresh frozen human tissue samples and 292 human cell lines by microarray analysis. In addition, we used a sensitive RT-PCR strategy to define the expression of SEPT9 isoforms in archival formalin-fixed and paraffin-embedded normal human tissues. The mRNA data were further confirmed by immunohistological analyses of SEPT9 protein expression in normal human tissues using antisera that detect SEPT9 isoforms. Using these complementary approaches, we demonstrate that SEPT9 mRNA and protein are expressed ubiquitously, with the isoforms showing tissue-specific expression. The microarray analysis indicates that there is consistent overexpression of SEPT9 in diverse human tumours including breast, CNS, endometrium, kidney, liver, lung, lymphoid, oesophagus, ovary, pancreas, skin, soft tissue and thyroid. Since tumours are commonly associated with enhanced cell proliferation, we examined the possible correlation of Ki67 and SEPT9 expression in normal tissues and tumours. Our data indicate that the overexpression of SEPT9 in neoplasia is not simply a proliferation-associated phenomenon, despite its role in cytokinesis.

Cell Movement↗

Three-dimensional dosimetry for intralesional radionuclide therapy using mathematical modeling and multimodality imaging.

UNLABELLED: A method of dosimetry is described that quantifies the three-dimensional absorbed-dose distribution resulting from an intralesional administration of a radiolabeled monoclonal antibody, allowing for both spatial and temporal heterogeneity of distribution of the radionuclide and without the need for a calibration scan. METHODS: A mathematical model was developed to describe the distribution of activity as a function of time resulting from infusion at a single point within the solid component of a tumor. The parameters required for this model are either known directly or may be obtained from SPECT image data registered to computed tomography. Convolution of this distribution with a point-source dose kernel enabled the three-dimensional absorbed-dose distribution to be obtained. RESULTS: This method was applied to a set of patient data acquired in the course of a clinical study performed at our center, and dose profiles and dose-volume histograms were produced. It was shown that the three-dimensional distribution of dose was significantly nonuniform. CONCLUSION: Initial results suggest that this method offers a means of determining the absorbed dose distribution within a tumor resulting from intralesional infusion. This method extends the Medical Internal Radiation Dose computation, which, in these circumstances, would make erroneous assumptions. Furthermore, it will enable individual patient treatment planning and optimization of the parameters that are within the clinician's control.

Humans↗

Paradoxical scalp lateralization of the P100 cognitive somatic potential in humans: a magnetic field study.

In somatic selective attention, electrical brain mapping disclosed a P100 cognitive electrogenesis with a scalp field paradoxically lateralized ipsilaterally to the target finger stimulus. We used 64 sensors magnetoencephalography (MEG) and source localization software in six normal humans to identify the P100 neural generator. Calculated dipole sources for P100 were iteratively compared with the recorded MEG data. The equivalent dipole at somatic P100 latency was located in the parietal lobe contralateral to the finger stimulus and had an oblique positive gradient pointing towards the ipsilateral side, thus explaining the paradoxical positivity in electrical brain mapping. It is suggested that the somatic P100 is generated in parietal area 7b which indeed appears to be specialized for cognitive processing within the somatic modality rather than for multimodal association.

Brain Mapping↗

Architectonics of the human cerebral cortex and transmitter receptor fingerprints: reconciling functional neuroanatomy and neurochemistry.

The density of transmitter receptors varies between different locations in the human cerebral cortex. We hypothesized that this variation may reflect the cyto- and myeloarchitectonical as well as the functional organisation of the cortex. We compared data from different imaging modalities (postmortem studies: cyto- and myeloarchitecture, quantitative in vitro receptor autoradiography; in vivo studies: PET receptor neuroimaging) in order to test our hypothesis. The regional and laminar distribution of the densities of numerous receptor types representing all classical transmitter systems as well as the adenosine system are visualized and measured in different cortical areas. The receptor distribution patterns segregate motor, primary sensory, unimodal sensory, multimodal association and other functionally identified cortical areas from each other. Areas of similar function show similar receptor fingerprints and differ from those with other properties. Thus, receptor distribution patterns reflect an organisational structure strictly correlated with the architectonics and functions of the human cerebral cortex.

Aged↗

[Clinical characteristics and neurophysiologic findings in patients with multiple sclerosis without oligoclonal IgG in cerebrospinal fluid].

INTRODUCTION: Besides magnetic resonance imaging, the presence of locally produced oligoclonal IgG bands (OCB) in the cerebrospinal fluid (CSF) is the most consistent laboratory abnormality in patients with multiple sclerosis (MS). The most sensitive method for the detection of CSF OCB is isoelectric focusing (IEF) [6]. Occasional patients with clinically definite MS lack evidence for intrathecal IgG synthesis [7, 8]. This study was designed to compare clinical data and evoked potential (EP) findings between CSF OCB positive and OCB negative MS patients. PATIENTS AND METHODS: The study comprised 22 OCB negative patients with clinically definite MS [11] and 22 OCB positive controls matched for age, disease duration, activity and course of MS. In both groups clinical assessment was performed by using Expanded Disability Status Scale (EDSS) score [12] and progression rate (PR). All patients underwent multimodal EP: visual (VEPs), brainstem auditory (BAEPs) and median somatosensory (mSEPs). The VEPa were considered abnormal if the P100 latency exceeded 117 ms or inter-ocular difference greater than 8 ms was detected. The BAEPs were considered abnormal if waves III or V were absent or the interpeak latencies I-III, III-V, or I-V were increased. The mSEPs were considered abnormal when N9, N13 and N20 potentials were absent or when increased interpeak latencies were recorded. The severity of the neurophysiological abnormalities was scored for each modality as follows: normal EP score 0; every other EP abnormality except the absence of one of the main waves, score 1; absence of one or more of the main waves, score 2 [13]. RESULTS: Both mean EDSS score (4.0 vs. 3.5) and PR (0.6 vs. 0.5) were similar in OCB positive and OCB negative group, (p > 0.05). In the first group males were predominant, but without statistical significance (Table 1). Disease started more often with the brainstem symptoms in the OCB positive than in OCB negative MS group (p = 0.028), while there was no differences in other initial symptoms between the groups (Graph 2). The frequency of (multimodal) EP abnormalities was higher in the OCB positive group but the differences were not statistically significant, except for bilateral SEP abnormalities (p = 0.012). The severity of the AEPs abnormalities was similar in both groups while for the VEPs and SEPs abnormalities were more pronounced in the OCB positive group but not significantly (Table 2). DISCUSSION: The male preponderance of OCB negative MS patients in our study is in accordance with previous studies [14, 15]. This finding could be potentially ascribed to the well known gender-related differences in both humoral and cellular immune responses [17]. We found no statistically significant differences in either disability or PR between the two patient groups, although OCB negative MS patients had lower EDSS score and PR than OCB positive cases. In accordance with these findings, Fukazawa et al. also failed to show differences in disability between OCB negative and positive MS patients. On the other hand, few studies reported that OCB negative MS patients have a better prognosis [16, 18]. The only clinical difference between two groups of patients that we found was that the disease more often started with brainstem symptoms in OCB positive MS patients (p = 0.028). OCB positive MS patients had more often bilateral SEPs abnormalities (p = 0.012). There was no statistically significant differences between two groups of patients in the severity of trimodal EPs abnormalities and the frequency of BAEPs and VEPs abnormalities although OCB negative patients had trend towards less pronounced EP disturbancies. CONCLUSION: Our results did not reveal significant difference in clinical and neurophysiological(y) parameters between two groups of patients. However, they indicate a trend towards better prognosis of the disease in OCB negative MS patients.

Adult↗

DNA content and proliferative activity in pediatric genitourinary rhabdomyosarcoma.

Most of the studies have reported that cases of pediatric rhabdomyosarcoma (RMS) with hyperdiploid DNA and low cellular proliferative activity have better outcomes. The aim of our study was to evaluate the possible clinical relevance of DNA ploidy and proliferative activity in childhood genitourinary RMS. Twelve childhood genitourinary RMS cases were reexamined histologically and correlated with clinical features and patient survival. DNA analysis was performed on cytospin single-cell preparations obtained from the paraffin-embedded tissue blocks. MIB-1 was the proliferative marker used on paraffin sections. All patients were male with a mean age at diagnosis of 65 months. There were 5 tumors on the bladder, 5 on the pàratesticular region, and 2 on the prostate. All cases were treated with multimodality therapy using the protocols proposed by the International Society of Pediatric Oncology. The following subtypes of RMS were recognized: embryonal (n=6), spindle cell (n=4), and botryoid (n=2). DNA hyperdiploid was detected in 11 tumors (92%) and high MIB-1 index (>19%) in 4 cases (33%). Now, 10 patients are alive without evidence of disease and 2 patients are alive with evidence of disease. Our data suggested that childhood RMS of the genitourinary tract are preponderantly DNA hyperdiploid and have low cellular proliferative activity. It is also interesting that 83% of our genitourinary pediatric RMS patients are alive. As consequence of this study, we propose that DNA content and proliferative activity is a useful method to supplement findings in children with RMS.

Adolescent↗

The National Cancer Data Base report on colorectal cancer.

BACKGROUND: Previous Commission on Cancer studies have examined time trends in stage of disease, treatment patterns, and survival for colorectal cancer. Reported herein are the most current 1993 National Cancer Data Base (NCDB) data on colorectal cancer. METHODS: Two "calls for data," one in 1990 and one in 1991, have yielded a total of 71,560 colon cancer reports and 33,409 rectal cancer reports from hospital registries across the country. RESULTS: For colon cancer, continuation of the time trend toward proximal migration was reported. For both colon and rectal cancer, American Joint Committee on Cancer staging was used increasingly as the standard of appropriate cancer diagnosis. Increased use of multimodal treatment was reported for both colon and rectal cancers. African-American and non-Hispanic white, low-income patients were reported to have later stages of both colon and rectal cancers. CONCLUSIONS: The NCDB provides a useful longitudinal perspective on the diagnosis and treatment of colon and rectal cancers.

Adult↗

Cognitive-behavioral stress management reduces distress and 24-hour urinary free cortisol output among symptomatic HIV-infected gay men.

BACKGROUND: Stress management interventions can reduce symptoms of distress as well as modulate certain immune system components in persons infected with human immunodeficiency virus (HIV). These effects may occur in parallel with reductions in hypothalamic-pituitary-adrenal (HPA) axis hormones such as cortisol, which has been related in other work to a down-regulation of immune system components relevant to HIV infection. The present study tested the effects of a multimodal cognitive-behavioral stress management (CBSM) intervention on 24-hour urinary free cortisol levels and distressed mood in symptomatic HIV+ gay men. METHODS: Symptomatic HIV-infected gay men who were randomized to either a 10-week group-based CBSM intervention or a 10-week wait-list period provided psychological responses and urine samples pre-post intervention. RESULTS: Of the 59 participants providing matched questionnaire data, men assigned to CBSM (n = 40) showed significantly lower posttreatment levels of self-reported depressed affect, anxiety, anger, and confusion than those in the wait-list control group (n = 19). Among the 47 men providing urine samples (34 CBSM, 13 controls), those assigned to CBSM revealed significantly less cortisol output as compared to controls. At the individual level, depressed mood decreases paralleled cortisol reductions over this period across the entire sample. CONCLUSION: A time-limited CBSM intervention reduced distress symptoms and urinary free cortisol output in symptomatic HIV+ gay men and greater reductions in some aspects of distress, especially depressed mood, paralleled greater decreases in cortisol over the intervention period. If persisting stressors and depressed mood contribute to chronic HPA axis activation in HIV-infected persons, then interventions such as CBSM, which teaches them to relax, alter cognitive appraisals, use new coping strategies, and access social support resources, may decrease distress and depressed mood and normalize HPA axis functioning.

Adult↗

Indicators of functional status for primary malignant brain tumour patients.

BACKGROUND: We compared the functional status and survival time of patients with malignant gliomas. METHODS: This retrospective review included 143 patients diagnosed with malignant gliomas. Patients were grouped according to histopathological diagnosis. To measure functional status, patients were assigned a Karnofksy performance status (KPS) score at the time of presentation and at one, three, six, nine, 12 months and yearly intervals thereafter. Data were analyzed using descriptive methods as well as Kruskal-Wallis tests, Chi-square tests, Log-Rank tests and Cox's proportional hazards modeling. RESULTS: Eighty-four patients were male. The median age of patients was 63 years. One hundred and seven patients had a histopathological diagnosis of glioblastoma multiforme, 23 of anaplastic astrocytoma and 13 of anaplastic oligodendroglioma. Twenty-nine patients received aggressive multimodal treatment, 83 received intermediate treatment and the remaining 31 patients received conservative therapy. Significant treatment complications occurred in 33% of patients including four post-operative deaths. The anaplastic oligodendroglioma group had lower mortality and maintained better KPS scores over time, as did patients receiving full treatment. The most significant prognostic factors for functional status included age, pretreatment KPS, and type of treatment received. The most significant factors associated with time until death included age, severity of comorbidities, pretreatment KPS, presence of confusion, histopathological diagnosis and type of treatment received. CONCLUSION: In patients with malignant gliomas, younger age, better functional status at presentation and aggressive multimodal treatment were associated with improved longer-term functional status and survival. Confirmation of the effect of multimodal treatment on patient functional status would require a randomised controlled clinical trial.

Adult↗

Lake Superior Rural Cancer Care Project, part I: an interventional trial.

PURPOSE: To date, effective cancer care and control intervention studies have been carried out largely in urban and suburban populations. This study was conducted to test innovative interventions, using experimental designs, to improve the care and outcomes of patients with cancer in rural settings. DESCRIPTION OF STUDY: The Lake Superior Rural Cancer Care Project (LSRCCP) tested an innovative, multimodal, multidisciplinary intervention that involved rural healthcare providers and their healthcare system. An experimental design was used, with the rural community as the unit of randomization. Outcomes were measured at three levels: rural providers' knowledge of cancer management, providers' practice performance, and patient outcomes. This 5-year study was conducted in rural areas of northern Minnesota, Wisconsin, and the western part of the Upper Peninsula of Michigan. RESULTS: Baseline data from the study are provided, and details of the design and methods are presented. The study outcomes are reported in part in "Lake Superior Rural Cancer Care Project Part II" in this issue and will be reported further in future issues. CLINICAL IMPLICATIONS: This article describes the hypotheses, design, and methods of the LSRCCP. The design and methods as well as the results of this study may be useful to cancer researchers and clinicians in rural areas across the United States.

Humans↗

Brain magnetic resonance imaging and multimodal evoked potentials in benign and secondary progressive multiple sclerosis.

Brain MRI and multimodal evoked potentials (EPs) were obtained for 13 patients with benign multiple sclerosis and 13 patients with secondary progressive multiple sclerosis, matched for age and duration of the disease, to investigate the nature of the disability in multiple sclerosis. Patients with secondary progressive multiple sclerosis had significantly greater lesion loads for five of seven periventricular regions and for three of nine regions separate from the ventricles. Patients with secondary progressive multiple sclerosis also had more severe infratentorial atrophy scores (p = 0.04), whereas there were no differences between the two groups in number and extent of enhancing lesions. The frequencies were significantly higher and severities greater for multimodal EP abnormalities of all the modalities in patients with secondary progressive multiple sclerosis. At least one EP component was absent in 12 (92%) patients with secondary progressive multiple sclerosis but in only one patient (8%) with benign multiple sclerosis (p < 0.001). There was neurophysiological evidence for cervical cord involvement in eight (61%) patients with secondary progressive multiple sclerosis and in one with benign multiple sclerosis (p < 0.01). These data indicate that the total amount of lesions, the distribution, and the nature of the pathological process might all account for the development of disability in multiple sclerosis.

Age of Onset↗

The diencephalon of the channel catfish, Ictalurus punctatus. II. Retinal, tectal, cerebellar and telencephalic connections.

In a companion paper, the nuclear organization of the diencephalon of the channel catfish, Ictalurus punctatus, was described and compared to that of other teleosts. The present paper describes the connections of the diencephalon with the retina, optic tectum, corpus of the cerebellum and telencephalon. The principal tracer employed is the indocarbocyanine dye DiI which diffuses along neuronal membranes in fixed tissues. Almost all of the nuclei that were recognized as distinct in the companion study are found to also exhibit distinct sets of connections. Most of these connections have not been described previously in catfishes or other teleosts. When combined with connectional data from the existing literature, the results of the present study allow one to recognize a great number of distinct pathways through the diencephalon of channel catfish, including several visual, auditory, gustatory, electrosensory and mechanosensory pathways to the telencephalon. Almost all of the species differences in diencephalic organization noted in the companion study can be accounted for by changes in one of the major sensory pathways. In contrast, the multimodal and integrative areas of the diencephalon appear to be relatively conservative. A comparison between the diencephalon of teleosts and that of other vertebrates suggests that the dorsal thalamus, the ventral thalamus and the posterior tuberculum are homologous, at least in part, to the dorsal thalamus, the zona incerta and the subthalamic nucleus of mammals, respectively. All three areas project to the telencephalon in both mammals and teleosts. In most vertebrates, however, the dorsal thalamus provides the dominant input to the telencephalon, whereas in teleosts the main telencephalic input derives instead from the posterior tuberculum.

Animals↗

Implementation of the Texas Medication Algorithm Project patient and family education program.

OBJECTIVE: This article describes the implementation and utilization of the patient and family education program (PFEP) component of the Texas Medication Algorithm Project (TMAP). The extent of participation, types of psychoeducation received, and predictors of receiving at least a minimum level of education are presented. METHOD: TMAP included medication guidelines, a dedicated clinical coordinator, standardized assessments of symptoms and side effects, uniform documentation, and a PFEP. The PFEP includes phased, multimodal, disorder-specific educational materials for patients and families. Participants were adult outpatients of 1 of 7 community mental health centers in Texas that were implementing the TMAP disease management package. Patients had DSM-IV clinical diagnoses of major depressive disorder, with or without psychotic features; bipolar I disorder or schizoaffective disorder, bipolar type; or schizophrenia or schizoaffective disorder. Assessments were administered by independent research coordinators. Study data were collected between March 1998 and March 2000, and patients participated for at least 1 year. RESULTS: Of the 487 participants, nearly all (95.1%) had at least 1 educational encounter, but only 53.6% of participants met criteria for "minimum exposure" to individual education interventions. Furthermore, only 31.0% participated in group education, and 42.5% had a family member involved in at least 1 encounter. Participants with schizophrenia were less involved in the PFEP across multiple indicators of utilization. Diagnosis, intensity of symptoms, age, and receipt of public assistance were related to the likelihood of exposure to minimum levels of individual education. CONCLUSION: Despite adequate resources and infrastructure to provide PFEP, utilization was less than anticipated. Although implementation guidelines were uniform across diagnoses, participants with schizophrenia experienced less exposure to psychoeducation. Recommendations for improving program implementation and modification of materials are discussed.

Adult↗

Multimodality preoperative treatment for advanced cancer of the head and neck.

Neoadjuvant induction chemotherapy with cisplatin, methotrexate, and bleomycin appears to improve the results of treatment of advanced stage IV head and neck cancer, compared with results in historical control subjects. Patients treated with induction chemotherapy and radiation therapy had a 29 percent overall survival rate at 3 years, which represents approximately a twofold improvement in the survival rate. Patients who were treated with chemotherapy and radiation therapy followed by surgery had more than a threefold increase in the survival rate (49 percent at 3 years), compared with historical data from our institution and elsewhere for such patients [9-11]. Distant metastases developed in 25 percent of the patients, and it thus appears that long-term, effective consolidation and maintenance chemotherapy [12,13] need to be developed for patients who receive combination therapy before surgery for head and neck cancer.

Actuarial Analysis↗

[Multimodal monitoring of head injuries in children].

As in the case of adults, there are three main goals in the monitoring of severe head trauma in children: to prevent or minimize the apparition of secondary lesions, to optimize treatment, to help make precise prognosis. The basic monitoring is composed of repeated clinical examinations, brain radiological imaging and control of vital parameters (blood pressure, temperature, PaO2 (SpO2), PaCO2 (FETCO2), haemoglobin, haematocrit. On the other hand, during specific brain monitoring, the brain perfusion (TCD, intracranial pressure), the electrical activity of the brain and sometimes the brain oxygenation (SvjO2) are controlled. The data obtained from the brain monitoring must always be interpreted carefully. A child with a severe head trauma, in ICU, always requires constant and competent medical attention.

Child↗