Evaluation of level I and II axillary nodes included in the standard breast tangential fields and calculation of the administered dose: results of a prospective study.

PURPOSE: To evaluate if Level I and II axillary nodes are included in the standard breast tangential fields, and to calculate the dose administered. METHODS AND MATERIALS: In 35 patients treated with conservative surgery and axillary dissection, three clips were surgically positioned: one at the beginning of Level I, one between Level I and II, and another at the end of Level II. The breast was irradiated with two tangential fields. On simulation films, the volume between the clips was scored as "entirely included" or "not entirely included" in the treatment fields. Computed tomography (CT) scans were performed; CT data were imported into a treatment planning system, and three-dimensional plans were devised. Axillary Levels I and II were delineated on CT slices on the basis of anatomic landmarks. Fields and isodose curves previously obtained were superimposed to calculate the dose administered to the first two axillary node levels and to 90% of both volumes. RESULTS: On X-rays, the volume between clips corresponding to Level I was completely included in the medial field in 66.7% of cases and in the lateral field in 63.7% of cases, whereas the volume of Level II was entirely included in the medial field in 54.5% of cases and in the lateral field in 45.4% of cases. The median dose administered to Level I and II was 38.58 Gy +/- 11.01 (range 3.46-47.14) and 20.65 Gy +/- 14.07 (range 0.95-38.94), respectively. The median dose to 90% of both volumes of Level I and II was 6.75 Gy +/- 14.01 (range 1.9-39) and 1.75 Gy +/- 9.72 (range 0.8-29), respectively. CONCLUSION: The standard tangential fields do not entirely include Levels I and II axillary nodes.

Regional node failure in patients with four or more positive lymph nodes submitted to conservative surgery followed by radiotherapy to the breast.

A retrospective analysis was conducted to evaluate the incidence of nodal failure in a subgroup of patients who had T1-T2 breast cancer and four or more positive nodes. Sixty-four 5 patients ranging in age from 29 to 73 years (median, 51) received conservative surgery followed by radiotherapy to the breast between November 1980 and May 1995. Adjuvant chemotherapy was administered to 56 patients, 27 of whom were also treated with tamoxifen, which was used alone in 5 patients. Three patients received no adjuvant treatment. Sixty-two patients are evaluable for regional node failure. There were 10 nodal failures, 4 in the axillary and 6 in the supraclavicular regions, in 9 patients, at a median of 56.5 and 27 months, respectively. There was no internal mammary node failure. Median follow-up was 72.6 months. The 10-year probability of developing axillary and supraclavicular failure is 13.9 +/- 7.7% and 10.5 +/- 4.1%, respectively. Prognosis was better for patients with axillary and breast recurrence and worse when relapse was in the supraclavicular region. On the basis of our results and data already published in premenopausal patients, we believe that radiotherapy to the supraclavicular region should be considered in patients with four or more positive axillary nodes, after a complete dissection.

Short-course palliative radiotherapy in non-small-cell lung cancer: results of a prospective study.

From February 1993 to October 1997, 91 consecutive patients with inoperable (stage IIIB-IV) histologically confirmed non-small-cell lung cancer underwent palliative hypofractionated radiotherapy. Recently, the Medical Research Council studies on hypofractionated short-course radiotherapy (8.5 Gy x 2) have reported high control of symptoms caused by thoracic disease without toxicity. Based on these experiences and our previous positive trial on short-course radiotherapy (8 Gy x 2) in metastatic spinal cord compression, a prospective study of short-course palliative radiotherapy in non-small-cell lung cancer was carried out. The regimen was 16 Gy given in two 8-Gy fractions, 1 week apart. Eighty-one patients were evaluable for response to treatment. Forty-eight (59%) patients were 65 years or older. Forty (49%) patients were naive to radiotherapy, whereas 41 (51%) had previous cisplatin-based chemotherapy. All but four stage IV patients (95%) had poor Eastern Cooperative Oncology Group performance status (i.e., 2-3). Clinical palliation was achieved in 62 (77%) patients. Performance status improved in 59 (73%) patients. The median palliation time ranged from 28% to 57% of patient survival. The median survival from the beginning of treatment was 148 days (range, 5-681 days). No difference in overall survival according to stage and previous chemotherapy was observed. Only performance status conditioned survival (performance status 1-2 vs. performance status 3; p = 0.0289). Short-course radiotherapy gave good results in terms of clinical palliation for thoracic symptoms, even in patients with poor performance status and pretreated with chemotherapy. The median palliation time was approximately 50% of patient survival time. Treatment was generally well tolerated-only 4 (5%) patients experienced World Health Organization grade III dysphagia. No late toxicity was recorded. The two-fraction regimen had social and economic advantages compared with the conventional ones.

Neuropsychological assessment of the severely impaired elderly patient: validation of the Italian short version of the Severe Impairment Battery (SIB). Gruppo di Studio sull'Invecchiamento Cerebrale della Società Italiana di Gerontologia e Geriatria.

One hundred and sixty-nine severely demented patients were tested in a multicenter study with the short version of the Severe Impairment Battery which was translated into Italian with the purpose of adapting and validating it for an Italian population. Patients were enrolled in Italian geriatric centers participating in the Study Group on Aging Brain of the Italian Society of Gerontology and Geriatrics. Following thorough clinical and instrumental examinations, they were evaluated with the Mini Mental State Examination, the Clinical Dementia Rating, the Severe Impairment Battery (SIB), the Gottfries-Bråne-Steen Rating Scale for Dementia, the Activity of Daily Living index, and the Bedford Alzheimer Nursing Severity scale (BANS.s). The inter-rater reliability of the SIB was highly significant for the total score and its subtests; test-retest reliability showed the same significance in all items. Also concurrent validity, performed comparing the total SIB score with the total BANS.s score, was significant. The short Italian version of the SIB proved to be a very reliable tool for the evaluation of severely demented patients; it has the advantage of being easy to administer, it evaluates more cognitive domains that, are typically assessed in dementia, and has a wide enough range of scores to detect even small differences in the examined abilities.

Tau protein in cerebrospinal fluid: a new diagnostic and prognostic marker in Alzheimer disease?

Tau is the main protein of paired helical filaments. It can be detected and measured in cerebrospinal fluid (CSF) and for this reason it has been proposed as a possible in vivo marker of Alzheimer disease (AD). To evaluate the usefulness of CSF tau in the diagnosis of AD we measured it in patients with AD, frontal lobe dementia (FLD), vascular dementia (VD), and in healthy controls by means of a specific enzyme-linked immunosorbent assay test. Individuals with AD had significantly higher tau levels than FLD, VD, and controls. Individuals with late onset AD had significantly higher levels than those with early onset disease. In AD, CSF tau level did not correlate with age, duration, or severity of the disease, whereas a correlation with age was found in FLD and controls. In the nine AD patients in whom CSF tau measurement was repeated after 2 years, mean levels did not differ from baseline, although a worsening of cognitive performances occurred. The overlap among the different groups and the absence of any modification over time suggest that CSF tau measurement, more than in confirming or staging overt AD, might be useful in revealing the disease at its preclinical phase.

Oxidative damage to DNA in lymphocytes from AD patients.

OBJECTIVE: Several studies show structural and functional alterations in peripheral cells in AD. The purpose of this study was to evaluate oxidative stress in AD lymphocytes. BACKGROUND: The literature supports the role of reactive oxygen species in the pathogenesis of AD because several markers of oxidative damage have been detected in AD brain. METHODS: 8-hydroxy-2'-deoxyguanosine (8OHdG), a marker of oxidative stress in DNA, was measured in lymphocytes of AD patients and healthy aged controls with high-pressure liquid chromatography with electrochemical detection, both at basal condition and after acute oxidative stress with hydrogen peroxide. RESULTS: A significantly higher concentration of 8OHdG in lymphocytes occurred in AD patients compared with controls. In this latter group, 8OHdG increased progressively with age. After acute oxidative stress, levels of formed 8OHdG did not differ between AD patients and controls. CONCLUSIONS: Our results support that AD is affected by oxidative stress, detectable not only in the brain but also in peripheral cells; oxidative mechanisms may contribute to the pathogenesis of AD. Additional studies in other neurodegenerative diseases are needed to evaluate these findings.

Interstitial pneumonitis in acute leukemia patients submitted to T-depleted matched and mismatched bone marrow transplantation.

PURPOSE: To identify factors that could contribute to interstitial pneumonitis (IP), which remains one of the major causes of morbidity and mortality after both matched and mismatched bone marrow transplantation (BMT). METHODS AND PATIENTS: Ninety acute leukemia patients received an allogeneic T-depleted matched (n = 54) or mismatched (n = 36) BMT. They were preconditioned with total body irradiation (TBI), thiotepa, rabbit anti-thymocyte globulin, and cyclophosphamide. The TBI scheme was hyperfractionated in matched, and a single dose in mismatched patients. The dose to the lungs was reduced in both groups. RESULTS: Five of the 54 matched patients developed IP. All cases were fatal. There were 16 cases of IP, 13 fatal, in the mismatched group. The probability of developing IP was 11.3 +/- 4.9% and 48.6 +/- 9.0%, respectively. The between-group difference was statistically significant (p < 0.0001). The type of transplant and the TBI scheme were the most important parameters for IP development in univariate analysis, whereas acute graft-versus-host disease, disease stage and sex were nonsignificant. Median follow-up was 342 days (range 17-2900). CONCLUSIONS: The low incidence of IP in matched patients and the lack of idiopathic cases are evidence for the validity of the TBI schedule. In contrast, the incidence in mismatched patients remains too high; therefore, new strategies should be studied in an attempt to lower it.

Stem cell mobilization in normal donors.

We studied peripheral blood and apheresis samples from 39 consecutive normal donors who were parents or siblings of patients who received matched or mismatched bone marrow transplants using a combination of rhG-CSF-mobilized peripheral blood stem cells (PBSCs) and bone marrow (BM). BM was harvested from donors 1-7 days before starting rhG-CSF treatment: 12 micrograms/kg/day rhG-CSF was administered by continuous s.c. infusion for 4-7 days. Peripheral blood progenitor cells were harvested by leukapheresis using an automated continuous-flow blood cell separator, beginning on day 4 of rhG/CSF, for 1-4 consecutive days. Peak peripheral blood CD34+ cell and CFU-GM levels were reached simultaneously on day 5 or 6 of rhG-CSF administration. Median peak levels were 1.65% for CD34+ cells (range 0.34%-4.7%) and 142 CFU-GM/10(5) plated cells (range 16-700). The greatest numbers of CD34+ cells and CFU-GM, expressed per liter of blood volume processed, were harvested during the second and third leukapheresis: CD34+ cells 37.77 +/- 25.48 x 10(6) and CFU-GM 3.32 +/- 2.51 x 10(6) during the second leukapheresis, and CD34+ cells 37.01 +/- 16.33 x 10(6) and CFU-GM 3.82 +/- 4.36 x 10(6) during the third. The number of CD34+ cells and CFU-GM did not correlate with the sex, age, or body weight of the donors. This study indicates that this protocol for administration of rhG-CSF mobilizes large numbers of hematopoietic progenitor cells into the peripheral blood and that bone marrow harvesting before G-CSF administration does not impair stem cell mobilization.

Mitochondrial membrane fluidity and oxidative damage to mitochondrial DNA in aged and AD human brain.

Oxidative damage on biological molecules has been proposed as a major cause of alterations observed in aging brain as well as in neurodegenerative diseases. In this study, we measured membrane fluidity in mitochondria extracted from three cerebral regions and cerebellum of Alzheimer disease (AD) patients and age-matched controls by means of fluorescence polarization technique. A significant reduction of mitochondrial membrane fluidity was found in AD, except in cerebellum. In controls, a decrease of membrane fluidity was observed along with age, and it was also related to the content of the oxidized nucleoside 8-hydroxy-2'-deoxyguanosine (OH8dG) in mitochondrial DNA (mtDNA). Alteration in membrane fluidity seems to be a result of lipid peroxidation, since it dramatically decreased when mitochondria were exposed to FeCl2 and H2O2. The parallel increase of viscosity in mitochondrial membrane and the amount of OH8dG in mtDNA is suggestive of a relationship between these biological markers of oxidative stress. These results provide further evidence that oxidative stress may play a role in the pathogenesis of AD.

Diagnosing Alzheimer's disease in very elderly patients. Relevance of some functional and psychobehavioral aspects assessed by the Gottfries-Bråne-Steen Rating Scale for Dementia. Study Group on Brain Aging, Italian Society of Gerontology and Geriatrics.

OBJECTIVES: To describe the Gottfries-Bråne-Steen (GBS) Rating Scale more fully with instruments commonly used for the diagnostic assessment of older patients with cognitive disturbances--the Mini Mental State Examination (MMSE), Hamilton Depression Rating Scale (HDRS), and Global Deterioration Scale (GDS)--and to characterize the specific diagnostic value of the GBS. DESIGN: A multicenter study including patients diagnosed with senile dementia of the Alzheimer type (SDAT; age at onset: > 75 years) and age-matched non-demented subjects. SUBJECTS: One hundred thirty-eight consecutively referred SDAT patients and 116 non-demented age-matched healthy subjects selected from among relatives of the patients. METHODS: The MMSE, GBS and HDRS were used for assessing patients and controls. The GDS was utilized for dementia staging. FINDINGS: Principal component analysis carried out on GBS scores yielded three factors explaining 74% of variance: factor 1, general functioning; factor 2, depression, and factor 3, restlessness. The actual composition of these factors was analyzed after computing factor scores for each subject by means of forward selection regressions, each using the MMSE, GDS and HDRS as predictors of scores on a given factor. The best predictors were MMSE and GDS scores for factor 1; HDRS for factor 2, and MMSE for factor 3. A GBS cutoff of 8 (obtained after a quality receiver operating characteristic analysis) best discriminated between demented and non-demented subjects (positive-predictive value: 0.88; negative-predictive value: 0.90). CONCLUSIONS: The GBS Rating Scale for dementia can be a useful tool in routine clinical assessment of older subjects with cognitive impairment and distinguishes between demented and non-demented subjects; it gives comprehensive information on functional and psychobehavioral characteristics of demented patients, being composed of factors related to the MMSE and HDRS.

Altered mitochondrial membrane fluidity in AD brain.

Oxidative damage on biological membranes has been proposed as a cause of the alterations observed in aging brain and, more severely, in Alzheimer's disease (AD). In this study we evaluated membrane fluidity of mitochondria extracted from different areas of normal and AD brains by means of fluorescence polarization technique. AD mitochondria showed a significant reduction of membrane fluidity compared to controls except in cerebellum. This might be caused by a greater lipid peroxidation of biological membranes, as suggested by in vitro experiments we performed to this purpose. From these results the possible role of oxidative stress in AD pathogenesis is supported.

Increased cerebrospinal fluid pyruvate levels in Alzheimer's disease.

Impaired energy metabolism is an early, predominant feature in Alzheimer's disease. In order to find out simple, reliable 'in vivo' markers for the clinical-biological typization of the disorder, we measured cerebrospinal fluid (CSF) glucose, lactate and pyruvate levels in patients suffering from dementia of Alzheimer type (DAT) and in healthy elderly controls. DAT group showed remarkably higher levels of pyruvate (P = 0.01), with no overlap with the values obtained in controls. CSF pyruvate levels were also significantly associated with the severity of dementia. Therefore, CSF pyruvate levels neatly separate DAT patients from controls, having also pathogenetic value.

Serum anti-GFAP and anti-S100 autoantibodies in brain aging, Alzheimer's disease and vascular dementia.

Autoantibodies against glial fibrillary acidic protein (GFAP) and S100 protein were measured in sera of patients suffering from vascular dementia (VD), presenile Alzheimer's disease (AD), senile Alzheimer's disease (SDAT) and aged healthy controls by means of ELISA test. VD and SDAT showed the highest levels of both autoantibodies, AD the lowest. From these results a relationship between autoantibody titers and aging seems possible. Dosage of anti-GFAP and anti-S100 autoantibodies does not appear useful for diagnostic purpose because of the overlap observed among groups. Rather, the presence of these antibodies seems to reflect an alteration of the blood-brain barrier that promotes the access of central nervous system antigens to immunocompetent cells.

Cerebrospinal fluid neuron-specific enolase in Alzheimer's disease and vascular dementia.

Levels of neuron-specific enolase (NSE), a glycolytic enzyme localized in neurons, were measured in serum and cerebrospinal fluid (CSF) of patients with early-onset (e-AD) and late-onset (l-AD) Alzheimer's disease, vascular dementia (VD) and controls. Mean CSF NSE levels in patients with Alzheimer's disease did not significantly differ from those in controls, although in the AD group a correlation was found between NSE levels and severity of cognitive deficits. In VD patients, CSF NSE was lower than in controls or in AD patients. These findings are of physiopathological interest but suggest that CSF NSE is not a useful biological marker in dementia disorders.

Prevalence of anti-HCV antibodies in patients with chronic liver disease and its relationship to HBV and HDV infections.

The prevalence of anti-HCV, anti-HDV and of HBV markers has been investigated in a series of 209 consecutive patients (age 18-74 years) with chronic liver disease. Among 155 HBsAg negative patients (53 chronic hepatitis cases and 102 cirrhosis cases), anti-HCV were found in 69% of the cases. 67% of the 155 patients also carried anti-HBc, with no difference between patients positive or negative for anti-HCV. Among the 54 HBsAg positive patients, 10 (18.5%) also had anti-HCV, 22 (40.7%) were anti-HDV positive and 12 (22.2%) had serum HBV-DNA. One patient had concomitant anti-HDV and anti-HCV and another presented anti-HCV and serum HBV-DNA. 21/54 patients had liver cirrhosis on presentation and among these 17 (81%) were anti-HCV and/or anti-HDV positive. On the whole, 123/209 patients had liver cirrhosis on presentation and in 107 of them HCV infection may have played a role.