Biomedical subjects

A Micheli

Publications and source records attributed to A Micheli.

At least 19 recordsLinked to original sources

PubMed2001

HIV-1 Nef activates STAT1 in human monocytes/macrophages through the release of soluble factors.

Monocytes/macrophages play a predominant role in the immunologic network by secreting and reacting to a wide range of soluble factors. Human immunodeficiency virus (HIV) infection leads to deep immunologic dysfunctions, also as a consequence of alterations in the pattern of cytokine release. Recent studies on in vivo models demonstrated that the expression of HIV Nef alone mimics many pathogenetic effects of HIV infection. In particular, Nef expression in monocytes/macrophages has been correlated with remarkable modifications in the pattern of secreted soluble factors, suggesting that the interaction of Nef with monocytes/macrophages plays a role in the pathogenesis of acquired immunodeficiency syndrome (AIDS). This study sought to define possible alterations in intracellular signaling induced by Nef in monocytes/macrophages. Results demonstrate that HIV-1 Nef specifically activates both alpha and beta isoforms of the signal transducer and activator of transcription 1 (STAT1). This was observed both by infecting human monocyte-derived macrophages (MDMs) with HIV-1 deletion mutants, and by exploiting the ability of MDMs to internalize soluble, recombinant Nef protein (rNef). STAT1-alpha activation occurs on phosphorylation of both C-terminal Tyr701 and Ser727 and leads to a strong binding activity. Nef-dependent STAT1 activation is followed by increased expression of both STAT1 and interferon regulatory factor-1, a transcription factor transcriptionally regulated by STAT1 activation. It was also established that Nef-induced STAT1- alpha/beta activation occurs through the secretion of soluble factors. Taken together, the results indicate that HIV-1 Nef could interfere with STAT1-governed intracellular signaling in human monocytes/macrophages.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Erythrocyte membrane fatty acids and subsequent breast cancer: a prospective Italian study.

BACKGROUND: The relationship between erythrocyte membrane fatty acids and postmenopausal breast cancer risk was analyzed previously only by retrospective studies, which suggested a protective effect of increased saturation index (SI), i.e., the ratio of membrane stearic to oleic acid. We investigated the relationships in a prospective study of hormones, diet, and prediagnostic breast cancer (the ORDET study) conducted in northern Italy. METHODS: A total of 4052 postmenopausal women were followed for an average of 5.5 years; 71 cases of invasive breast cancer were identified. For each case subject, two matched control subjects were chosen randomly from among cohort members. The various fatty acids in erythrocyte membranes were measured as a percentage of total fatty acids. Conditional logistic regression analysis evaluated the association between membrane fatty acid composition and breast cancer risk. The SI, which is influenced by the activity of the enzyme delta 9 desaturase (Delta 9-d), was also investigated. All statistical tests were two-sided. RESULTS: Oleic (highest versus lowest tertile of percentage of total fatty acids, odds ratio [OR] = 2.79; 95% confidence interval [CI] = 1.24 to 6.28) and monounsaturated fatty acids (highest to lowest tertile, OR = 5.21; 95% CI = 1.95 to 13.91) were positively associated with breast cancer risk. The SI (highest to lowest tertile, OR = 0.29; 95% CI = 0.13 to 0.64) was inversely associated with breast cancer risk. The analysis suggested an inverse association between total polyunsaturated fatty acids and breast cancer risk, but individual polyunsaturated fatty acids behaved differently. There was no association between saturated fatty acids and breast cancer risk. CONCLUSIONS: We have found that monounsaturated fats and SI in erythrocyte membranes are predictors of postmenopausal breast cancer. Both of these variables depend on the activity of the enzyme Delta 9-d. The dietary, metabolic, and hormonal factors acting on Delta 9-d expression and activity and, therefore, on patterns of fatty acid metabolism, should be further investigated as possible determinants of breast cancer.

Adult↗

PubMed2001

Axillary lymph node staging in breast cancer by 2-fluoro-2-deoxy-D-glucose-positron emission tomography: clinical evaluation and alternative management.

BACKGROUND: Surgical removal of axillary lymph node and histologic examination for metastases are used to determine whether adjuvant treatment is necessary for patients with breast cancer. Axillary lymph node dissection (ALND) is a costly procedure associated with various side effects, and 80% or more of patients with tumors of 20 mm or less are lymph node negative and might avoid ALND. In this study, we evaluated whether an alternative, noninvasive method--i.e., positron emission tomography (PET) with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG)-- could be used to determine axillary lymph node status in patients with breast cancer. METHODS: One hundred sixty-seven consecutive patients with breast cancers of 50 mm or less (range = 5-50 mm; mean = 21 mm) scheduled for complete ALND were studied preoperatively with FDG-PET, and then PET and pathology results from ALND were compared. All statistical tests were two-sided. RESULTS: The overall sensitivity, specificity, and accuracy of lymph node staging with PET were 94.4% (PET detected 68 of 72 patients with axillary involvement; 95% confidence interval [CI] = 86.0% to 98.2%), 86.3% (82 of 95 patients without axillary involvement; 95% CI = 77.8% to 91.9%), and 89.8% (150 of 167 patients with breast cancer; 95% CI = 84.2% to 93.6%), respectively. Positive- and negative-predictive values were 84.0% (68 patients with histologically positive lymph nodes of 81 patients with positive FDG-PET scan; 95% CI = 74.2% to 90.5%) and 95.3% (82 patients with histologically negative lymph nodes of 86 patients with negative FDG-PET scan; 95% CI = 88.2% to 98.5%), respectively. When PET results for axillary metastasis were analyzed by tumor size, the diagnostic accuracy was similar for all groups (86.0%-94.2%), with higher sensitivity for tumors of 21-50 mm (98.0%) and higher specificity for tumors of 10 mm or less (87.8%), and the range was 93.5%-97.3% for negative-predictive values and 54.5%-94.1% for positive-predictive values. Among the 72 patients with axillary involvement, PET detected three or fewer metastatic lymph nodes in 27 (37.5%) patients, about 80% of whom had no clinically palpable axillary lymph nodes. CONCLUSIONS: Noninvasive FDG-PET appears to be an accurate technique to predict axillary status in patients with breast cancer and thus to identify patients who might avoid ALND. These results should be confirmed in large multicenter studies.

Adult↗

PubMed2001

Incidence and prevalence of all cancerous diseases in Italy: trends and implications.

The burden of cancer in ageing populations is causing great concern, particularly in Italy with Europe's fastest growing elderly population. Studying all cancers combined in one group, although of limited medical value, is of great interest from the viewpoints of public health, epidemiology and the economy. Using mortality data and an estimate of cancer patients' survival we have estimated and projected incidence and prevalence in Italy of all cancers combined in one group. Five major phenomena are highlighted in the paper: (1) the decrease in the age-adjusted cancer mortality rates among females and the stable mortality rates among males since 1990; (2) the changing pattern of cancer incidence since 1990, it has started to decrease for females and is stabilising for males; (3) the decrease in cancer incidence among males and females born after 1940; (4) the increase in the proportion of cancer patients that are cured with calendar years of diagnosis; (5) the increase in the total and the healthy life expectancy (i.e. cancer-free) among the Italian population since 1970. The declining and flat trends in age-adjusted cancer incidence and mortality rates since 1990 is the combined effect of survival improvements and cancer risk reduction for younger cohort groups, after 1940. These favourable trends contribute to the increase in healthy life expectation, thus supporting the idea that we live longer and healthier.

Adolescent↗

PubMed2001

Cancer survival increases in Europe, but international differences remain wide.

The EUROCARE project analysed cancer survival data from 45 population-based cancer registries in 17 European countries, revealing wide international differences in cancer survival. We calculated 5-year relative survival for 1836287 patients diagnosed with one of 13 cancers during the period 1978-1989. The data, from 20 cancer registries in 13 countries, were grouped into four regions: Finland, Sweden, Iceland (Northern Europe); Denmark, England and Scotland (UK and Denmark); France, The Netherlands, Germany, Italy and Switzerland (Western Europe); Estonia and Poland (Eastern Europe), and broken down into four periods (1978-1980, 1981-1983, 1984-1986, 1987-1989). For each cancer, mean European and regional survival was estimated as the weighted mean of 5-year relative survival in each country. Survival increased with time for all tumours, particularly for cancers of testis (12% increase, i.e. from 79.9 to 91.9%), breast, large bowel, skin melanoma (approximately 9-10%), and lymphomas (approximately 7%). For most solid tumours, survival was highest in Northern Europe and lowest in Eastern Europe, and also low in the UK and Denmark. Regional variation was less marked for the lymphomas. Survival improved more in Western than Northern Europe, and the differences between these regions fell for bowel cancer (from 8.0% for those diagnosed in 1978-1980 to 2% for those diagnosed in 1987-1989), breast cancer (from 7.4% to 3.9%), skin melanoma (from 13.4% to 11.0%) and Hodgkin's disease (from 7.2 to 0.6%). For potentially curable malignancies such as Hodgkin's disease, large bowel, breast and testicular cancers, there were substantial increases in survival, suggesting an earlier diagnosis and more effective treatment. The persisting regional differences suggest there are corresponding differences in the availability of diagnostic and therapeutic facilities, and in the effectiveness of healthcare systems.

Adolescent↗

PubMed2001

Validity of hospital discharge diagnoses for the assessment of the prevalence and incidence of amyotrophic lateral sclerosis.

INTRODUCTION: As amyotrophic lateral sclerosis (ALS) is a rare neurological disorder, many sources must be investigated for complete case ascertainment. Hospital discharge diagnoses (HDDs) are a source of administrative data for patients hospitalized for a given disease. The accuracy of HDDs was tested, to assess whether they could be used to trace patients with amyotrophic lateral sclerosis (ALS). METHODS: All the HDDs referring to patients with motor neuron disease (MND) (ICD-9 code 335.2) were identified from primary hospital discharge diagnoses made during the years 1994-95 in six target provinces of the Lombardy region in Northern Italy (total population 2922920). The medical records of the patients were reviewed and each patient was then accepted or rejected according to whether he/she did or did not satisfy the El Escorial criteria for the diagnosis of ALS. The ALS discharge diagnoses filed in the study period in the neurology departments of all the regional hospitals were the 'gold standard'. Newly diagnosed patients registered during the year 1998 in the same provinces served for the calculation of the incidence of the disease. Sensitivity, specificity and positive predictive value were calculated. Data were presented separately for all the patients and those who were indicated as first hospital admissions. RESULTS: During the study period a total of 1012122 hospital discharge records were coded in the six index provinces. The ICD-9 code 335.2 was reported in 408 of these (0.04%). These discharge diagnoses were made in 267 patients, 245 of whom were resident in Lombardy at the time of hospital admission. The hospital records of 237 cases were examined. In 95 of these the medical records showed a diagnosis other than ALS. Other motor neuron diseases were listed for 50 patients. Thirteen additional cases were traced through neurology department files. The sensitivity of the HDDs was 91.6%, the specificity 99.9%, the positive predictive value 65.4%. The corresponding values for first-hospitalized patients were 97.7, 99.9, and 37.3. The overall ALS incidence rate obtained from the HDDs was 2.1 per 100000 (95% CI 1.3-3.3). he corresponding rate calculated after exclusion of the false positives and inclusion of the false negatives was 0.8 (95% CI 0.1-2.1) and that obtained using the 1998 cases registered in the same areas was 1.6 (95% CI 0.7-2.7). CONCLUSIONS: The incidence of ALS is overestimated when HDDs are used for the estimate. Nevertheless, with improved quality, administrative data could be useful for the estimate of prevalence and incidence.

Admitting Department, Hospital↗

PubMed2000

Fatty acid composition of the red blood cell membrane in relation to menopausal status.

PURPOSE: Menopausal status effects female anatomical functioning at a variety of system-wide and cellular levels, including cellular membrane composition. This study analyzed a nested case-control ORDET data set of 433 pre and post-menopausal breast cancer controls to examine the effects of menopausal status on the fatty acid composition of the red blood cell membrane.METHODS: ORDET is a prospective cohort study conducted in Italy to investigate the etiologic role of hormones and diet in breast cancer development. The fatty acid composition was measured and analyzed by gas chromotography, comparing retention time with standard measurement. Twenty-two individual fatty acids were measured, recorded, and categorized into four fatty acid groups: saturated, monounsaturated, polyunsaturated n-6 (PUFA n-6), and polyunsaturated (PUFA n-3) fatty acids.RESULTS: Post-menopausal women had consistently lower mean values for all four fatty acid categories and all individual fatty acids. Statistically significant mean differences, by menopausal status, were observed for three of the four fatty acid categories: saturated fatty acids (p = 0.006), PUFA n-6 acids (p = 0.001), and PUFA n-3 acids (p = 0.000). The biggest statistically significant differences in mean values among individual fatty acids for each category were observed for Palmitic acid (p = 0.009), Oleic acid (p = 0.040), Linoleic acid (p = 0.000), and Docosahexaenoic acid (p = 0.000). Individual fatty acids were also less highly correlated among post-menopausal women.CONCLUSIONS: There was an observed relationship between menopausal status and the fatty acid composition of the red blood cell membrane that warrants further study. This relationship may contribute to the physiological and psychological changes that occur during and after menopause, and may have far-reaching implications for women's health.

Journal Article↗

PubMed2000

Toward a comparison of survival in American and European cancer patients.

BACKGROUND: Only recently have extensive population-based cancer survival data become available in Europe, providing an opportunity to compare survival in Europe and the United States. METHODS: The authors considered 12 cancers: lung, breast, stomach, colon, rectum, melanoma, cervix uteri, corpus uteri, ovary, prostate, Hodgkin disease, and non-Hodgkin lymphoma. The authors analyzed 738,076 European and 282,398 U.S. patients, whose disease was diagnosed in 1985-1989, obtained from 41 EUROCARE cancer registries in 17 countries and 9 U.S. SEER registries. Relative survival was estimated to correct for competing causes of mortality. RESULTS: Europeans had significantly lower survival rates than U.S. patients for most cancers. Differences in 5-year relative survival rates were higher for prostate (56% vs. 81%), skin melanoma (76% vs. 86%), colon (47% vs. 60%), rectum (43% vs. 57%), breast (73% vs. 82%), and corpus uteri (73% vs. 83%). Survival declined with increasing age at diagnosis for most cancers in both the U.S. and Europe but was more marked in Europe. CONCLUSIONS: Survival for most major cancers was worse in Europe than the U.S. especially for older patients. Differences in data collection, analysis, and quality apparently had only marginal influences on survival rate differences. Further research is required to clarify the reasons for the survival rate differences.

Adolescent↗

PubMed2000

Circulating levels of tumour necrosis factor-alpha and its soluble receptors are increased in the blood of patients with amyotrophic lateral sclerosis.

An immunologic pathogenesis for amyotrophic lateral sclerosis (ALS) has been recently proposed. We tested the whole tumour necrosis factor (TNF) system in the serum of 51 ALS patients at different stages of the disease and 36 healthy controls. Antigenic TNF-alpha and its soluble receptors (sTNF-Rs), measured by ELISA, were significantly higher in ALS patients than in healthy controls. However, biologically active TNF-alpha, corresponding to the sTNF-Rs-unbound trimeric TNFalpha molecule and assayed by its cytotoxic activity on a sensitive cell line, was similar between ALS patients and healthy controls. Neither antigenic TNF-alpha, bioactive TNF-alpha nor sTNF-Rs correlated with disease severity, disease duration, or weight loss. In conclusion, we reported an activation of the TNF system in ALS. The role of this activation in the pathogenesis of the disease remains elusive.

Amyotrophic Lateral Sclerosis↗

PubMed2000

Impact of blunted pulmonary venous flow on the outcome of patients with left ventricular systolic dysfunction secondary to either ischemic or idiopathic dilated cardiomyopathy.

The intravenous administration of echo contrast agents enhances the Doppler signal and makes the study of pulmonary venous flow (PVF) easily achievable by transthoracic echocardiography. The aim of this study was to evaluate whether PVF patterns play a role in predicting the outcome of patients with left ventricular (LV) systolic dysfunction. Thus, 115 patients (79 men, mean age 69 years) with LV dysfunction (ejection fraction [EF] <45%) due to either ischemic or idiopathic dilated cardiomyopathy were studied and followed-up for 1 year. A quantitative interrogation of all components of PVF was feasible in 69% of patients at standard transthoracic examination; after contrast enhancement, anterograde and retrograde flow velocities were measurable in 100% and 92% of patients, respectively. A blunted PVF (defined by a systolic-to-diastolic peak velocity ratio <1) was identified in 48 patients (42%), who had a worse clinical status, a lower LVEF, and a more severe pulmonary hypertension. Thirty-six patients had cardiac events at follow-up: sudden death in 4, progressive heart failure in 12, and hospitalization for worsening heart failure in 20 patients. Multivariate Cox proportional-hazards analysis revealed that advanced New York Heart Association class, male gender, and older age were independent predictors of mortality. However, blunted PVF, reduced LVEF, older age, and increased heart rate in descending order of power were independent predictors of heart failure hospitalizations and deaths from end-stage heart failure. In conclusion, the assessments of PVF may effectively contribute to the characterization of patients with LV dysfunction and to the prediction of their outcome.

Aged↗

PubMed2000

A randomized controlled trial of recombinant interferon beta-1a in ALS. Italian Amyotrophic Lateral Sclerosis Study Group.

OBJECTIVE: To evaluate the efficacy of recombinant interferon beta (IFNbeta)-1a in the treatment of ALS. BACKGROUND: It has been proposed that IFNs affect the progression of ALS by interfering with putative immune mechanisms involved in the pathogenesis of the disease. METHODS: Patients (n = 61) 40 to 70 years of age with a 6- to 24-month history of confirmed ALS with mild to moderate disability received IFNbeta-1a, 12 mIU (n = 31), or placebo (n = 30) subcutaneously three times a week for 6 months and were followed up for an additional 6 months. Patients were assessed after 4, 12, 24, 36, and 48 weeks. Medical Research Council scale, Norris scale, and bulbar scores as well as forced vital capacity were used to assess disability. Selected electrophysiologic measures (latency, amplitude, and duration of the compound muscle action potential) were also used. RESULTS: Twenty patients randomized to IFNbeta-1a and 17 patients given placebo completed the study. A total of 16 patients receiving IFNbeta-1a became non-self-supporting compared with 16 on placebo (52% versus 53%). There were no significant differences between the two treatment groups for any of the measures of disease progression and disability. Deaths were reported in six patients treated with IFNbeta-1a and four patients on placebo. Adverse events were reported more frequently with IFNbeta-1a (77% of patients) compared with placebo (57%), with flu-like symptoms and local erythema being the commonest complaints. CONCLUSIONS: This pilot study suggests that IFNbeta-1a is not effective in the treatment of ALS.

Aged↗

PubMed2000

Markers of insulin resistance and sex steroid hormone activity in relation to breast cancer risk: a prospective analysis of abdominal adiposity, sebum production, and hirsutism (Italy).

OBJECTIVE: Insulin resistance and increased levels of serum steroids have been hypothesized to be relevant etiological factors for breast cancer. Measurements of markers of insulin resistance and elevated serum steroids may identify women at high risk for breast cancer. The present study analyzed the association of breast cancer with markers of insulin resistance and elevated serum sex steroids, abdominal adiposity, increase in sebum production and hirsutism in a case-control study nested in a prospective cohort study. METHODS: Between 1987 and 1992, 10,786 women (aged 35-69) were recruited in a prospective study on breast cancer in Italy, the ORDET study. Women with a history of cancer and on hormone therapy were excluded at baseline. At recruitment, abdominal adiposity was calculated from the ratio of waist-to-hip circumferences. Sebum production was measured on the forehead under standardized conditions using a sebumeter. Nine androgen-sensitive body areas were evaluated for hirsutism and a total hirsutism score was computed. After an average of 5.5 years of follow-up, 144 breast cancer cases were identified among the participants of the cohort. For each breast cancer case, four matched controls were randomly chosen from members of the cohort who did not develop breast cancer during the follow-up period. RESULTS: Waist-to-hip ratio was associated with breast cancer in premenopausal women: age and body mass index (BMI) adjusted relative risk (RR) for the highest tertile of waist-to-hip ratio was 2.2 [95% confidence interval (CI) 1.04-4.75], p for trend 0.03. In the analysis conducted within strata of BMI, the effect of waist-to-hip ratio was confined to the group of thinner women: RR for the highest tertile of waist-to-hip ratio was 3.4 (95% CI 1.2-9.5). Sebum production and hirsutism were associated with breast cancer among postmenopausal women. Age and BMI adjusted RRs for the upper tertiles were 2.2 (95% CI 1.1-4.6), p for trend 0.01, and 2.3 (95% CI 1.1-4.9), p for trend 0.03, for sebum and hirsutism, respectively. CONCLUSION: These results add evidence for a role of hormones and metabolic alterations in breast cancer etiology and for different relations of these risk factors with breast cancer in premenopausal and postmenopausal women.

Abdomen↗

PubMed2000

Estrogen metabolism and risk of breast cancer: a prospective study of the 2:16alpha-hydroxyestrone ratio in premenopausal and postmenopausal women.

Experimental and clinical evidence suggests that 16alpha-hydroxylated estrogen metabolites, biologically strong estrogens, are associated with breast cancer risk, while 2-hydroxylated metabolites, with lower estrogenic activity, are weakly related to this disease. This study analyzes the association of breast cancer risk with estrogen metabolism, expressed as the ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone, in a prospective nested case-control study. Between 1987 and 1992, 10,786 women (ages 35-69 years) were recruited to a prospective study on breast cancer in Italy, the "Hormones and Diet in the Etiology of Breast Cancer" (ORDET) study. Women with a history of cancer and women on hormone therapy were excluded at baseline. At recruitment, overnight urine was collected from all participants and stored at -80 degrees C. After an average of 5.5 years of follow-up, 144 breast cancer cases and four matched controls for each case were identified among the participants of the cohort. Among premenopausal women, a higher ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone at baseline was associated with a reduced risk of breast cancer: women in the highest quintile of the ratio had an adjusted odds ratio (OR) for breast cancer of 0.58 [95% confidence interval (CI) = 0.25-1.34]. The corresponding adjusted OR in postmenopausal women was 1.29 (95% CI = 0.53-3.10). Results of this prospective study support the hypothesis that the estrogen metabolism pathway favoring 2-hydroxylation over 16alpha-hydroxylation is associated with a reduced risk of invasive breast cancer risk in premenopausal women.

Adult↗

PubMed1999

Variations in survival for invasive cervical cancer among European women, 1978-89. EUROCARE Working Group.

OBJECTIVES: To analyze cervical cancer survival trends in 10 European countries using models that estimate the proportion of cured patients (having the same life expectancy as the general population) and the survival of fatal cases (who die from cervical cancer). METHODS: We considered 40,906 cases diagnosed over 12 years (1978-89) collected from cancer registries participating in EUROCARE. RESULTS: From 1978 to 1989, 5-year relative survival in Europe improved (60%-->63%). The proportion of cured patients increased slightly but significantly (53%-->55%, p = 0.05). For countries with poorer survival at the end of the 1970s the proportion of cured patients increased faster than average, particularly evident in England (49%-->56%) and Scotland (44%-->53%). By contrast, in Finland, Sweden and Germany with organized screening, 5-year survival and cure rate did not improve, but incidence declined to very low levels. CONCLUSIONS: Cervical screening can explain the trends in cervical cancer survival: this identifies premalignant lesions, reduces incidence and selectively prevents less aggressive cancers. The decreased proportion of the latter means that survival does not improve in countries with low incidence of cervical cancer. The increased proportion of cured patients with time shows that survival improvement was not due simply to earlier diagnosis with no patient advantage.

Adolescent↗

PubMed1998

Radiation therapy in the management of symptomatic bone metastases: the effect of total dose and histology on pain relief and response duration.

PURPOSE: In order to better define variables and factors that may influence the pain response to radiation, and to look for a radiation regimen that can assure the highest percentage and the longest duration of pain relief, we performed a prospective, although not randomized, study on patients with bone metastases from various primary sites. METHODS AND MATERIALS: From December 1988 to March 1994, 205 patients with a total of 255 solitary or multiple bone metastases from several primary tumors were treated in our radiotherapy center with palliative intent. Irradiation fields were treated with three main fractionation schedules: (1) Conventional fractionation: 40-46 Gy/20-23 fractions in 5-5.5 weeks; (2) Short course: 30-36 Gy/10-12 fractions in 2-2.3 weeks; (3) Fast course: 8-28 Gy/1-4 consecutive fractions. Pain intensity was self-assessed by patients using a visual analogic scale graduated from 0 (no pain) to 10 (the strongest pain one can experience). Analgesic requirement was assessed by using a five-point scale, scoring both analgesic strength and frequency (0 = no drug or occasional nonopioids; 1 = Nonopioids once daily; 2 = Nonopioids more than once daily; 3 = Mild opioids (oral codeine, pentazocine, etc.), once daily; 4 = Mild opioids more than once daily; 5 = Strong opioids (morphine, meperidine, etc.). Complete pain relief meant the achievement of a score < or = 2 in the pain scale or 0 in the analgesic requirement scale. Partial pain relief indicated a score of 3 to 4 or of 1 to 2 on the former and latter scale, respectively. RESULTS: Total pain relief (complete + partial) was observed in 195 (76%) sites, in 158 of which (62%) a complete response was obtained. Metastases from NSC lung tumors appeared to be the least responsive among all primary tumors, with 46% complete pain relief in comparison to 65% and 83% complete relief in breast (p = 0.04) and in prostate metastases (p = 0.002), respectively. A significant difference in pain relief was detected among the several ranges of total dose delivered to the painful metastases, with 81%, 65%, and 46% complete relief rates in the 40-46 Gy, 30-36 Gy (p = 0.03), and 8-28 Gy (p = 0.0001) dose ranges respectively. A straight correlation between total dose and complete pain relief was confirmed by the curve calculated by the logistic model which shows that doses of 30 Gy or more are necessary to achieve complete pain relief in 70% or more of bone metastases. This correlation holds also for the duration of pain control, as shown by the actuarial analysis of time to pain progression. Multivariate analyses, with complete pain relief and time to pain progression as endpoints show a highly significant effect of radiation dose (p = 0.0007) and performance status (p = 0.003), with lower rates of complete pain relief and shorter time to pain progression observed after smaller radiation total doses or higher Eastern Cooperative Oncology Group (ECOG) scores. CONCLUSION: Although single-dose or short course irradiation is an attractive treatment in reducing the number of multiple visits to radiotherapy departments for patients with painful bone metastases, it is nevertheless clear that aggressive protracted treatments seem to offer significant advantages especially for patients in whom the expected life span is not short.

Analgesics↗

PubMed1998

Survival of women with breast cancer in Europe: variation with age, year of diagnosis and country. The EUROCARE Working Group.

Breast cancer is the most frequent malignancy among women in developed countries. Prognosis is better than for other major cancers, and an improvement in survival has been reported for several populations in recent decades. Within the framework of EUROCARE, a population-based project concerned with the survival and care of cancer patients in Europe, we analysed data from 119,139 women diagnosed with breast cancer between 1978 and 1985 in 12 countries and followed for at least 6 years. Multiple regression models of relative survival, which take mortality from all other causes in each area into account, were used to estimate the effect of age, period of diagnosis and country on survival. For the comparison between countries, survival rates were age-standardised to the age structure of the entire study population. Women aged 40-49 years at diagnosis had the best prognosis in all countries and throughout the study period. Women younger than 30 years at diagnosis had a worse prognosis than those aged 30-39. The highest relative survival at 5 years was in Finland and Switzerland (about 74%), intermediate levels were found for Italy, France, The Netherlands, Denmark and Germany (about 70%) and the lowest rates were in Spain, the United Kingdom, Estonia and Poland (55-64%). During the 6 months following diagnosis, survival was highly dependent on age and was sharply lower in women older than 49 years. For women surviving more than 6 months after diagnosis, survival was similar for all ages, although women aged 40-49 still had the better prognosis. The average rate of death from breast cancer fell by about 2.5% for each year of diagnosis between 1978 and 1985. This improvement manifested mainly in younger and older women, for whom survival was initially less good. The largest improvement was seen in Poland (-15% death risk per year). We suggest that the better survival of women aged 40-49 at diagnosis is related to lower levels of circulating sex hormones, resulting in reduced stimulation of tumour cell growth. Early diagnosis may also be important in the peri-menopausal period due to increased diagnostic attention. Low survival in the United Kingdom may be due to inadequate adherence to consensus treatment guidelines and greater variation in treatment.

Adult↗

PubMed1998

The cure for colon cancer: results from the EUROCARE study.

The interpretation of time trends and geographical differences of population-based survival rates is generally not easy, due to the difficulty in disentangling the effects of observational biases, diagnostic and therapeutic procedures and their interactions. Whereas descriptive analysis of relative survival is generally based on survival levels estimated at fixed time since diagnosis, interpretation issues can take advantage from the analysis of the shape of the considered relative survival. Parametric survival models allowing the estimation of the fraction of cured patients are applied here to analyze and discuss the differences in colon cancer relative survival between European countries, according to age and period of diagnosis. The survival curves of colon cancer patients are described according to 2 parameters: the proportion of cured patients and the mean survival time of fatal cases. These parameters are estimated by least square nonlinear regression of relative survival values derived from the EUROCARE Project publication. Exponential and Weibull survival functions are used to model the relative survival curve for the fraction of fatal cases. The Weibull model gives generally a better fit with respect to the exponential model, thus indicating that the mortality rate for fatal cases is decreasing with time since diagnosis. For the youngest patients, however, the 2 survival functions give practically overlapping estimates. The overall proportion of colon cancer patients in Europe that are estimated to be cured was 38.6%. This proportion increased from 36% to 40% for patients diagnosed in 1978-1980 and in 1983-1985, respectively. Accordingly, mean survival time of fatal cases increased from 1.18 to 1.52 years. According to age, the proportion of cured patients present a marked decrease from young (48.4% at age 15-44 years) to middle-aged patients (38.6% at age 5564 years) and only a mild decrease from these to the oldest patients (34.4% at age 75 or more). The opposite effect was shown by survival time of fatal cases, i.e., 1.71, 1.75 and 0.77 years for the same age classes, respectively. Proportion of cured cases and mean survival time of fatal cases tended to be positively correlated with each other across countries. Our results are consistent with the hypothesis that a real improvement in colon cancer survival took place in Europe during the years 1978-1985 and also suggest that the well-known decrease of relative survival with age at diagnosis could be mostly due to a decreasing efficacy of early diagnosis for patients under 60 years old and to less effective therapies for older patients.

Adult↗

PubMed1998

Quantitative electroencephalography in amyotrophic lateral sclerosis.

OBJECTIVES: The authors evaluated quantitative EEG (QEEG) in patients with amyotrophic lateral sclerosis (ALS), in order to see if the confined cortical degeneration found in anatomical and functional examinations of central (rolandic) regions could give rise to abnormalities of cortical electrical activity. MATERIAL AND METHODS: Eighteen patients with ALS were compared with 14 control subjects comparable for age and sex. The QEEG analysis was blind to the clinical data. Frequency analysis of 30 EEG epochs, each of 2.6 s duration, was performed. RESULTS: QEEG in ALS patients showed a significant well-localized decrease of alpha activity only in the central regions, while theta and delta relative power did not show any difference from controls. CONCLUSION: We suggest that QEEG is able to show evidence of subtle EEG changes probably due to loss of cells in the somatomotor cortex selectively affecting the generator sites.

Adult↗