Free to total PSA ratio is not a reliable predictor of prostate biopsy outcome

AIMS AND BACKGROUND: The aim of this study was to assess the validity of predictors of prostate biopsy outcome in order to improve their positive predictive value. MATERIAL AND METHODS: The study material consisted of a consecutive series of 410 prostate biopsies performed during 2003. The variables tested as possible predictors were age, findings at palpation (DRE) and ultrasonography (TRUS), total prostate-specific antigen (PSA), and free-to-total prostate-specific antigen (F/T) ratio. The association with biopsy outcome (cancer vs non-cancer) was investigated by univariate and multivariate analysis. RESULTS: All tested variables showed a statistically significant and independent association with biopsy outcome both in univariate and multivariate analysis. Nevertheless, no variable had good performance as a biopsy indicator: depending on the considered variable, three to nine cancer biopsies would be delayed in order to avoid ten benign biopsies. Using 0.12, 0.15 and 0.20 as the cutoff for F/T would avoid 77.3%, 64.4% and 43.1% of benign biopsies but would delay 54.0%, 35.6% and 21.0% of cancer biopsies, respectively. CONCLUSION: Although it may contribute to diagnostic suspicion, F/T should never exclude a biopsy indicated because of suspicion arising from other diagnostic tests.     

Effect of filgrastim on serum lactate dehydrogenase and alkaline phosphatase values in early breast cancer patients

To improve chemotherapy dose intensity and to optimize the use of granulocyte-colony stimulating factor, 506 patients with early breast cancer were randomly assigned to high dose epirubicin and cyclophospamide (EC) with or without prophylactic subcutaneously filgrastim, according to 5 different schedules: 480 µg or 300 µg daily or every other day, on day 8 through day 14, and 300 µg daily on days 8 and 12 of each chemotherapy course, Serum levels of lactate dehydrogenase (LDH) and alkaline phosphatase (AP) were significantly higher in patients given EC plus filgrastim than EC alone (P + 0.0001), the rate of G1-3 toxicity being 33.4% and 13.1% vs. 1.6% and 1%, respectively. No clinical evidence of filgrastim-related hepatic damage or significant difference in transaminase and γ-GT elevation was seen between the two groups. LDH and AP closely resembled peripheral blood leukocytes count and increased with increasing leucocytosis, throughout the 5 schedules. Although no patient continued treatment for filgrastim-related side effects, and LDH and AP rises resolved spontaneously within 3 weeks following the chemotherapy course, physicians should be aware of the transient and innocuous change in serum chemistry associated to leucocytosis, since it could be misinterpreted as expression of disease activity.     

Imbalance of antioxidant enzymes in tumor cells and inhibition of proliferation and malignant features by scavenging hydrogen peroxide

The aim of this study was to evaluate the endogenous alterations of the antioxidant enzymes in tumor cells and to specifically compensate the resulting changes in the levels of reactive oxygen species (ROS) to control the malignant growth. We determined and compared the activities of antioxidant enzymes and the levels of superoxide anion (O2*-) and hydrogen peroxide (H2O2) in tumor cell lines with different degrees of malignancy, paired with regard to their origin (PB/CH72T4, PDV/PDVC57, and HBL-100/MCF-7). An increase in superoxide dismutase activity and a decrease in the activities of H2O2-detoxifying enzymes, as a function of malignancy, coupled with a rise in H2O2 and a decrease in O2*- were demonstrated. Treatment of cells with exogenous catalase showed a dose-dependent inhibition of proliferation. This inhibition was also demonstrated in several cell lines of different tissue origin and species, suggesting a general role of H2O2 in cell proliferation. Moreover, stable expression of human catalase in MCF-7 cells inhibited proliferation and also reverted malignant features. We conclude that H2O2 played a crucial and general role in the regulation of proliferation and that an endogenous imbalance in antioxidant enzymes could be a relevant event in the carcinogenesis process.     

Geographic clustering of residence in early life and subsequent risk of breast cancer (United States)

ObjectiveThis study focused on geographic clustering of breast cancer based on residence in early life and identified spatio-temporal clustering of cases and controls. Methods: Data were drawn from the WEB study (Western New York Exposures and Breast Cancer Study), a population-based case–control study of incident, pathologically confirmed breast cancer (1996–2001) in Erie and Niagara counties. Controls were frequency-matched to cases on age, race, and county of residence. All cases and controls used in the study provided lifetime residential histories. The k-function difference between cases and controls was used to identify spatial clustering patterns of residence in early life. Results: We found that the evidence for clustered residences at birth and at menarche was stronger than that for first birth or other time periods in adult life. Residences for pre-menopausal cases were more clustered than for controls at the time of birth and menarche. We also identified the size and geographic location of birth and menarche clusters in the study area, and found increased breast cancer risk for pre-menopausal women whose residence was within the cluster compared to those living elsewhere at the time of birth. Conclusion: This study provides evidence that early environmental exposures may be related to breast cancer risk, especially for pre-menopausal women.     

Electroneurography index based on nerve conduction study data: method and findings in control subjects

We developed a summary score of data obtained from nerve conduction studies (NCS). The principle of such approach is that when a nonrandom trend to lower amplitudes or conduction velocities is present, it may be revealed by a summary nerve conduction score. In a group of normal subjects, peroneal, sural, ulnar, and superficial radial nerves were studied; age- and height-related F-wave and soleus H-reflex latencies were also examined. Z-scores of distal latencies, amplitudes, conduction velocities, F-wave latencies, and H-index were averaged in order to obtain three electroneurography (ENG) indices: a simple arithmetic (ENG index 1) and two weighted means (index 2 and index 3), assigning a double or triple weight to lower limb z-scores. Reference limits were established using multiple regression equations of ENG indices against age and height. This technique could be useful in providing a better cut-off between normal and diseased populations and in improving test-retest variability of NCS when follow-up studies are required.     

Relationships of age at onset with clinical features and cognitive functions in a sample of schizophrenia patients

BACKGROUND: A number of studies investigated the relationships of age at onset with clinical presentation and cognitive performance of schizophrenic patients. The aim of the present study was to assess demographic and clinical characteristics; psychopathologic, social functioning, and quality-of-life ratings; and neuropsychological measures in a sample of patients with stabilized schizophrenia and to identify which factors independently contributed to a multiple regression model with age at onset as the dependent variable. METHOD: Ninety-six consecutive outpatients with schizophrenia (DSM-IV-TR criteria) were included in the study. Assessment instruments were as follows: a semistructured interview, the Clinical Global Impressions scale, the Comprehensive Psychopathological Rating Scale, and the Positive and Negative Syndrome Scale (PANSS) for psycho-pathology of schizophrenia; the Calgary Depression Scale for Schizophrenia (CDSS) for depression; the Social and Occupational Functioning Assessment Scale and the Sheehan Disability Scale for social functioning; the Quality of Life Scale; and a neuro-psychological battery including the Wisconsin Card Sorting Test (WCST) and the Continuous Performance Test. Two models of multiple regression were tested: the first included clinical features and psychopathologic, social functioning, and quality-of-life scales; the second also considered neuro-psychological variables. Data were collected from October 2001 to November 2002. RESULTS: The first multiple regression showed that age at onset was significantly related to scores on the PANSS subscale for negative symptoms (p =.042) and the CDSS (p =.041); the second regression found a relation of age at onset with PANSS score for negative symptoms (p =.002) and 2 neuropsychological measures, number of preservative errors on the WCST and Continuous Performance Test reaction time (p =.0005 for both). CONCLUSION: Our data indicate that, when results of neuropsychological tests are considered, early age at onset of schizophrenia is associated with severity of negative symptoms and compromised cognitive measures of executive functioning and sustained attention.     

Prion deposition in olfactory biopsy of sporadic Creutzfeldt-Jakob disease

Currently, definite peripheral markers for the in vivo diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) are not available. Here, we report the presence of pathological prion protein in the olfactory mucosa of a case with sporadic Creutzfeldt-Jakob disease. Prion protein immunoreactivity was detected in an olfactory biopsy performed 45 days after the disease onset, suggesting that the involvement of olfactory epithelium is an early event in sporadic Creutzfeldt-Jakob disease.     

Constitutive and induced neurogenesis in the adult mammalian brain: manipulation of endogenous precursors toward CNS repair

Over most of the past century of modern neuroscience, it was thought that the adult brain was completely incapable of generating new neurons. During the past 3 decades, research exploring potential neuronal replacement therapies has focused on replacing lost neurons by transplanting cells or grafting tissue into diseased regions of the brain. However, in the last decade, the development of new techniques has resulted in an explosion of new research showing that neurogenesis, the birth of new neurons, normally occurs in two limited and specific regions of the adult mammalian brain and that there are significant numbers of multipotent neural precursors in many parts of the adult mammalian brain. Recent advances in our understanding of related events of neural development and plasticity, including the role of radial glia in developmental neurogenesis and the ability of endogenous precursors present in the adult brain to be induced to produce neurons and partially repopulate brain regions affected by neurodegenerative processes, have led to fundamental changes in the views about how the brain develops as well as to approaches by which endogenous precursors might be recruited to repair the adult brain. Recruitment of new neurons can be induced in a region-specific, layer-specific and neuronal-type-specific manner, and, in some cases, newly recruited neurons can form long-distance connections to appropriate targets. Elucidation of the relevant molecular controls may both allow control over transplanted precursor cells and potentially allow the development of neuronal replacement therapies for neurodegenerative disease and other CNS injuries that do not require transplantation of exogenous cells.     

Lymphoblastoid cell lines of Rett syndrome patients exposed to oxidative-stress-induced apoptosis

Despite the identification of mutations in the methyl CpG binding protein 2 gene, the pathogenesis of Rett syndrome (RS) is still unknown. In order to clarify the role of apoptosis in this disorder, we studied lymphoblastoid cell lines in five classical RS patients and five controls, incubated with 2-deoxy-d-ribose (dRib), a reducing sugar that induces apoptosis in human cells, through oxidative damage. The apoptotic response was detected by flow cytometric analysis and agarose gel electrophoresis. The cells of RS patients showed a lower percentage of apoptosis in a routine condition than those of controls did, whereas, in the presence of dRib, the percentage of apoptotic cells in RS patients increased with time and reached the same percentage of those of controls at 72 h. The data observed here suggest that RS may have a low susceptibility or an increased resistance to the apoptotic cell death, which may be corrected only in the presence of a strong apoptotic stimulus.     

Nasu-Hakola disease: a rare entity in Italy. Critical review of the literature

Nasu-Hakola disease (NHD, polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, PLOSL) is a recessively inherited disorder characterized by systemic bone cysts and progressive presenile dementia associated with sclerosing encephalopathy. The disease has a worldwide distribution, but most patients have been reported in Finland and in Japan; in Italy there are anecdotal reports. The combination of neuropsychiatric symptoms and bone cysts is unique to this disease, which we believe to be underestimated in Italy. The molecular defect has been identified in loss-of-function mutations in the TYROBP gene in Finnish and in Japanese patients, and in the TREM2 gene in other families of different ethnic origins. We reviewed the international literature to define better the diagnostic steps and to draw the attention of neurologists and orthopaedic specialists to the disease. The identification of new cases followed by appropriate genetic counselling, genetic analysis, and study of the territorial distribution of affected patients could be a good strategy to follow in order to improve understanding of the disease.