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PubMed2006

Risk of cancer treatment-associated bone loss and fractures among women with breast cancer receiving aromatase inhibitors.

BACKGROUND: Aromatase inhibitors (AIs) are a novel hormonal therapy for patients with breast cancer. However, AIs can cause bone loss by blocking estrogen production. This study aims to assess the association between AIs and treatment-related bone loss in a large managed-care population of women with breast cancer. PATIENTS AND METHODS: With use of medical and pharmacy claims, data from > 5 million beneficiaries between January 1, 1998, and January 31, 2005, we identified 12,368 patients with > or = 2 breast cancer claims in a 6-month period who also had no bone metastases and no previous osteoporosis or fracture claims. Patients who had received antiestrogen (eg, tamoxifen) therapy were also excluded. One thousand three hundred fifty-four patients receiving an AI (anastrozole, exemestane, or letrozole) were compared with 11,014 controls who did not receive an AI with respect to their risk of bone loss. The observation start date for the AI and control groups was defined as the service date of the first AI claim and breast cancer claim, respectively. The endpoints include (1) bone loss, consisting of osteoporosis or osteopenia, and (2) clinical fractures. RESULTS: The univariate analysis found that the prevalence of bone loss was 8.7% in the AI group versus 7.1% in the control group, resulting in a significant relative risk of 1.3 (95% confidence interval [CI], 1.1-1.6; P = 0.01). The prevalence of bone fracture was also significantly increased in the AI group compared with the controls (13.5% vs. 10.3%) with a relative risk of 1.4 (95% CI, 1.2-1.6, P = 0.001). Multivariate Cox proportional hazards regressions showed that after adjusting for age and comorbidities, the risk of bone loss remained significantly higher in the AI group than in the non-AI group, with a 27% (95% CI, 4%-55%; P = 0.02) and 21% (95% CI, 3%-43%; P = 0.02) increase in the risk of bone loss and fractures, respectively. CONCLUSION: This retrospective longitudinal analysis of a large cohort of patients with breast cancer corroborates previous findings from smaller clinical trials and demonstrates that AI therapies carry an increased risk of bone loss. Monitoring and treatment management strategies to reduce bone loss risk are warranted in women receiving an AI for breast cancer.

Aged↗
PubMed2005

Bioluminescent human breast cancer cell lines that permit rapid and sensitive in vivo detection of mammary tumors and multiple metastases in immune deficient mice.

INTRODUCTION: Our goal was to generate xenograft mouse models of human breast cancer based on luciferase-expressing MDA-MB-231 tumor cells that would provide rapid mammary tumor growth; produce metastasis to clinically relevant tissues such as lymph nodes, lung, and bone; and permit sensitive in vivo detection of both primary and secondary tumor sites by bioluminescent imaging. METHOD: Two clonal cell sublines of human MDA-MB-231 cells that stably expressed firefly luciferase were isolated following transfection of the parental cells with luciferase cDNA. Each subline was passaged once or twice in vivo to enhance primary tumor growth and to increase metastasis. The resulting luciferase-expressing D3H1 and D3H2LN cells were analyzed for long-term bioluminescent stability, primary tumor growth, and distal metastasis to lymph nodes, lungs, bone and soft tissues by bioluminescent imaging. Cells were injected into the mammary fat pad of nude and nude-beige mice or were delivered systemically via intracardiac injection. Metastasis was also evaluated by ex vivo imaging and histologic analysis postmortem. RESULTS: The D3H1 and D3H2LN cell lines exhibited long-term stable luciferase expression for up to 4-6 months of accumulative tumor growth time in vivo. Bioluminescent imaging quantified primary mammary fat pad tumor development and detected early spontaneous lymph node metastasis in vivo. Increased frequency of spontaneous lymph node metastasis was observed with D3H2LN tumors as compared with D3H1 tumors. With postmortem ex vivo imaging, we detected additional lung micrometastasis in mice with D3H2LN mammary tumors. Subsequent histologic evaluation of tissue sections from lymph nodes and lung lobes confirmed spontaneous tumor metastasis at these sites. Following intracardiac injection of the MDA-MB-231-luc tumor cells, early metastasis to skeletal tissues, lymph nodes, brain and various visceral organs was detected. Weekly in vivo imaging data permitted longitudinal analysis of metastasis at multiple sites simultaneously. Ex vivo imaging data from sampled tissues verified both skeletal and multiple soft tissue tumor metastasis. CONCLUSION: This study characterized two new bioluminescent MDA-MB-231-luc human breast carcinoma cell lines with enhanced tumor growth and widespread metastasis in mice. Their application to current xenograft models of breast cancer offers rapid and highly sensitive detection options for preclinical assessment of anticancer therapies in vivo.

Animals↗
PubMed1992

Polyclonal expansion of T-cell receptor-gamma delta+ T lymphocytes associated with neutropenia and thrombocytopenia.

A patient with large granular lymphocyte (LGL) expansion (T-gamma lymphocytosis), neutropenia and thrombocytopenia was studied longitudinally. Analysis of peripheral blood mononuclear cells (PBMC) demonstrated an unusual large proportion of CD3+ T-lymphocytes expressing a gamma delta T-cell receptor (TcR-gamma delta). Immunofluorescence (IF) stainings with subset-specific monoclonal antibodies showed a fluctuating expansion of TcR-gamma delta+ T-cells expressing V gamma 9 and V delta 2 variable (V) gene segments. Biochemical characterization of PBMC showed the presence of a disulphide-linked TcR-gamma delta. TcR gene rearrangement studies on sorted TcR-gamma delta+ T-cells showed rearrangements of V gamma 9-J gamma 1.2 and V delta 2-J delta 1 V and joining (J) gene segments, thereby confirming the IF staining results. These data alone did not allow us to determine whether the TcR-gamma delta+ LGL expansion represented a polyclonal or monoclonal proliferation, because the combinatorial repertoire of TcR-gamma delta receptors is limited due to the availability of only a few V and J segments within the TcR-gamma and TcR-delta genes and because of the preferential usage of V gamma 9-J gamma 1.2 and V delta 2-J delta 1 rearrangements by TcR-gamma delta+ T-cells in blood of healthy individuals. We therefore used polymerase chain reaction (PCR)-mediated amplification of the TcR-gamma delta rearrangements, using specific V gamma 9, J gamma 1.2, V delta 2, and J delta 1 oligonucleotides to determine the junctional diversity of the TcR-gamma delta+ T-cell population. Sequence analysis of the PCR products obtained revealed a mixture of different junctional region sequences compatible with a polyclonal expansion. This is in contrast to the few reported TcR-gamma delta+ LGL and the majority of TcR-alpha beta+ LGL expansions, which appeared to consist of monoclonal proliferations.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1996

Self-assessment of disease activity by patients with rheumatoid arthritis.

OBJECTIVE: To determine the reliability of self-assessment of disease by patients with rheumatoid arthritis (RA), with a particular emphasis on the assessment of articular swelling. METHODS: A questionnaire was developed using components from validated instruments. Information was obtained on global function, global joint tenderness/swelling, and joint pain (10 cm visual analog scales), duration of musculoskeletal morning stiffness (grade 1-6), ACR functional score (grade 1-4), tender joint count (0-20), tender joint score (0-60), swollen joint count (0-20), and swollen joint score (0-60). Data were collected prospectively on 61 patients with RA in a teaching clinic or office practice by 4 staff rheumatologists. Patient questionnaires were completed within 24 h before physician assessments. Followup assessments were carried out on 27 patients after a mean interval of 3 months (range 0.5-6). RESULTS: At the initial assessment there was a significant correlation between patient and physician assessments for global function (r = 0.83; p = 0.01) [intraclass correlation coefficient (ICC) = 0.83; p < 0.01], global joint tenderness/swelling (r = 0.83; p < 0.01) (ICC = 0.83; p < 0.01), global joint pain (r = 0.83; p < 0.01) (ICC = 0.81; p < 0.01), duration of morning stiffness (r = 0.83; p < 0.01) (ICC = 0.85; p < 0.01), ACR functional score (r = 0.61; p < 0.01) (ICC = 0.62; p < 0.01), tender joint count (r = 0.57; p < 0.01) (ICC = 0.31; p < 0.01), and tender joint score (r = 0.60; p < 0.01) (ICC = 0.35; p < 0.01). However, there was poor correlation between patient and physician assessments for both swollen joint count (r = 0.16; p > 0.05) (ICC = -0.02; p > 0.05) and swollen joint score (r = 0.24; p > 0.05) (ICC = 0.12; p > 0.05). Longitudinal analysis indicated significant correlation between changes in patient and physician assessments in all variables except swollen joint count and score. CONCLUSION: Although there was good correlation between most variables for patient and physician assessments of disease activity in RA, there were substantial differences in the assessment of joint swelling. This objective determinant of disease activity cannot be ascertained in self-report measures of health status.

Adult↗
PubMed1994

The development of transplant coronary artery disease after cardiac transplantation is correlated with a predominance of CD8+ T lymphocytes in endomyocardial biopsy derived T cell cultures.

Long-term survival of heart transplant recipients is limited by the development of transplant coronary artery disease (TCAD). We analysed whether the development of TCAD is correlated with the incidence of acute rejection episodes, with the formation of anti-HLA antibodies or with the composition and function of T lymphocyte cultures derived from endomyocardial biopsies. TCAD was assessed by visual analysis of annually performed coronary angiograms and defined as the presence of all vascular changes, including minor wall irregularities. One year after transplantation, 31 of the 77 patients studied had TCAD (40%). The median age and mean number of HLA mismatches in patients with or without TCAD were highly comparable. The patient groups did not differ in incidence of acute rejection episodes, nor in percentage of endomyocardial biopsies yielding T cell cultures. At 1 year after transplantation, lymphocyte cultures from 18/31 TCAD+ patients (58%) and 27/46 TCAD- patients (57%) were analysed. The TCAD+ patients had, compared with the TCAD- patients, a higher median percentage of CD8+ T cells (71% versus 25%, P = 0.06) and a lower median percentage of CD4+ T cells (4% versus 40%, P = 0.04). Similar differences were found in a longitudinal analysis of the culture results of endomyocardial biopsies (EMBs) obtained during the first year. The cytotoxic reactivity of the cultures against donor HLA class I or class II antigens was comparable in the two groups, although a difference in recognition of heart specific antigens remains possible. The fact that EMB-derived cultures from TCAD+ and TCAD- patients differed in T cell phenotype populations gives some support to the hypothesis that cellular immunological processes are involved in the development of TCAD. However, while the median values differed, the overlap of the percentages of CD8+ cells in cultures from TCAD- and TCAD+ patients shows that other factors besides CD8+ T cells also play a role.

Adolescent↗
PubMed1999

No safe haven. II: The effects of violence exposure on urban youth.

OBJECTIVES: To examine the moderating effects of gender, grade level, and ethnicity on the associations between violence exposure and adolescents' internalizing symptoms and externalizing behavior and to explore whether such relationships persist over time. METHOD: A survey of adolescents' exposure to violence, internalizing symptoms, and externalizing behavior was administered to 2 cross-sectional samples of 6th, 8th, and 10th graders (N = 2,748 in 1994 and 2,600 in 1996) in an urban school system. Approximately 1,100 adolescents participated in both surveys and served as the longitudinal sample. RESULTS: Structural equation models indicated that violence exposure was closely associated with both externalizing behavior (r = 0.74-0.79) and internalizing symptoms (r = 0.36-0.38). The strength of association was similar across gender and ethnic groups. However, violence exposure was more closely related with internalizing symptoms for younger adolescents than their older counterparts. The longitudinal analysis suggested that exposure to violence reported at time 1 was related to adolescents' internalizing symptoms and externalizing behavior 2 years later. CONCLUSIONS: These results document high levels of violence exposure for urban youths and indicate links to a range of psychiatric symptoms and indicators of poor adjustment. Such findings carry implications for direct clinical work with young people, as well as for program development and public policy.

Adolescent↗
PubMed2002

Interaction between the C(-344)T polymorphism of CYP11B2 and age in the regulation of blood pressure and plasma aldosterone levels: cross-sectional and longitudinal findings of the Olivetti Prospective Heart Study.

OBJECTIVE: To study the interaction between the C(-344)T polymorphism and known determinants (age, body mass and dietary sodium) of blood pressure and plasma aldosterone. DESIGN: Cross-sectional and longitudinal (1980-1995) survey of male workers in southern Italy. SETTING: Medical centre of the Olivetti factories. PARTICIPANTS: In 1995, the C(-344)T polymorphism was characterized in 811 untreated men. A subgroup of 280 participants already seen in 1980 was the object of longitudinal analysis. MAIN OUTCOME MEASURES: Blood pressure, demographic, anthropometric and biochemical variables (serum and urinary electrolytes and plasma aldosterone) and frequency of the C(-344)T polymorphism. RESULTS: In the whole population, there was no difference among genotypes for any of the variables examined. However, multiple regression showed a significant interaction between age (but not body mass or sodium intake) and genotype with regard to systolic (P = 0.03) and diastolic ( P= 0.02) pressure variability independently of covariates. Diastolic pressure increased linearly with age in carriers of the T allele (TT, P<0.001 and TC, P= 0.005), but not in CC homozygotes ( P= 0.848). In T carriers - but not in CC homozygotes - blood pressure and serum potassium increased and plasma aldosterone and serum sodium decreased across quintiles of age (P< 0.001 for all trends). In the longitudinal study, diastolic pressure increased significantly over time only in T carriers (TC+TT: +2.6 +/- 0.6, versus CC: -0.4 +/- 1.5 mmHg, P= 0.04). CONCLUSION: Inter-individual variation of blood pressure and plasma aldosterone is affected by the interaction of C(-344)T polymorphism and ageing, thus supporting a role for this variant in mechanisms affecting blood pressure regulation.

Aging↗
PubMed2005

Body mass index and health among Union Army veterans: 1891-1905.

This paper explores the relationship between BMI and several health conditions among Union Army veterans who had medical examinations between 1891 and 1905. We find that BMI, when used as a proxy of nutrition, helps to explain morbidity and mortality differentials among veterans. There is evidence suggesting that among Union Army veterans extremely low or high BMIs were both associated with poor health, as indicated by a higher level of disability rating, higher risk of developing certain diseases, and higher mortality risk than those associated with having normal weight. Compared to veterans with normal weight, underweight veterans were more likely to be diagnosed with cardiovascular, respiratory and gastrointestinal diseases, but were less likely to be diagnosed with rheumatic and musculo-skeletal conditions at the first examination. High BMI levels are also associated with a higher risk of developing cardiovascular and rheumatic diseases, and higher mortality in the 20 years after the first examination. We performed a longitudinal analysis to study the association between earlier BMI as well as weight change and later development of diseases. The results suggest that, as a predictor of diseases, the explanatory power of BMI becomes lower the farther into the future we try to predict. Compared with those who maintained the same weight, veterans who gained weight were associated with a lower risk of being diagnosed with gastrointestinal diseases at their second examination.

Adult↗
PubMedDate not supplied

Monitoring of peripheral blood cytotoxic T-cells under fluvastatin treatment in renal transplant recipients.

Flow cytometric T-cell analysis is capable of adding valuable information for balancing immunosuppression in transplant recipients as it can take into account individual effects of immunosuppressive drugs on each patient as well as effects of other drugs which may modify the overall immunosuppression. Studies suggest that HMG-CoA-reductase-inhibitors (statins) reduce the frequency of organ rejection, although the precise mechanism of this effect is unknown. We therefore evaluated the effect of fluvastatin on size and activation of T-cell subpopulations and NK-cell activity in renal transplant recipients. At baseline, the population size of activated (HLA-DR+) T-cells was negatively correlated to serum HDL cholesterol suggesting an increased T-cell activation at low HDL levels. Fluvastatin treatment of a hypercholesterolemic group of patients for two months significantly decreased the LDL cholesterol. A longitudinal analysis revealed a relative increase in non-MHC restricted cytotoxic T-cells (CD3+/CD16+ or CD56+) over time which was significantly attenuated in fluvastatin treated patients but not in normocholesterolemic controls. Moreover, a relative decrease of activated MHC class I-restricted cytotoxic CD8+ T-cells was only observed upon fluvastatin treatment. NK-cell number and activity did not differ between groups. In summary, fluvastatin treatment of hypercholesterolemic renal transplant recipients is associated with a specific modulation of T-cells exerting cytotoxic effector functions.

Adult↗
PubMed2005

Enrollment of older persons in cancer trials after the medicare reimbursement policy change.

BACKGROUND: The Medicare program was revised in 2000 to authorize payment of routine care costs for patients in clinical trials. This study evaluates the impact of the Medicare reimbursement policy change on enrollment of older patients into cancer trials. METHODS: We conducted a longitudinal analysis of the enrollment of older patients in National Cancer Institute-sponsored lung, colorectal, breast, and prostate cancer trials from January 1996 through June 2003. Our primary analysis was restricted to 23 trials that were actively accruing before and after the Medicare change, enrolled more than 100 patients, and had at least 5% of participants older than 65 years. We used multivariate logistic regression to determine whether the proportion of participants who were elderly increased after the policy change. RESULTS: The primary study sample consisted of 16,135 patients in 23 trials. After adjusting for cancer type, trial exclusion criteria, and patient sociodemographic characteristics in multivariate analysis, no significant change occurred in the representation of older patients after the policy change (adjusted odds of participants being elderly after vs before policy change, 1.13; 95% confidence interval, 0.96-1.32; P = .14). In a secondary analysis of patients who had enrolled in any trial during the study period, no significant change occurred in enrollment of older persons after the policy change among phase 3 or phase 1 and 2 trial participants (P = .84 and P = .07 in adjusted analyses, respectively). CONCLUSION: The Medicare trial reimbursement policy was not associated with a significant increase in the enrollment of older patients in cancer trials.

Age Distribution↗
PubMed1994

Pulmonary function of a firemen-diver population: a longitudinal study.

Non smoking, male professional firemen-divers (n = 20) underwent two pulmonary function tests (PFT) separated by 8-9 years. Measured data were compared to European Coal Steel Community recommended reference values to permit cross-sectional and then longitudinal studies. Higher vital capacity (VC) and forced expiratory volume in 1 s (FEV1; both P < 0.001), and lower residual volume (P < 0.01) were observed in both PFT. Longitudinal analysis showed a smaller VC reduction than FEV1 reduction, leading to a FEV1/VC percentage decrease with time. Maximal mid expiratory flow (MMEF) and MMEF/VC changes during this 9-year period showed an unusually pronounced decrease, suggesting possible chronic effects of diving on small airways. Thus, it is suggested from our observations that a hyperbaric stimulus compensates in part for the effects of aging on VC and that obstructive disease could occur in subjects with long diving experience.

Adult↗
PubMed2006

Health literacy, antiretroviral adherence, and HIV-RNA suppression: a longitudinal perspective.

BACKGROUND: Low health literacy has been associated with worse adherence to antiretroviral therapy (ART) and higher HIV-RNA levels, but these relationships have not been evaluated in longitudinal analyses. METHODS: We evaluated literacy using the Rapid Estimate of Adult Literacy in Medicine (REALM) (< or = 6th grade, 7th to 8th grade, > or = 9th grade) in the HIV-Alcohol Longitudinal Cohort study of HIV-infected persons with a history of alcohol problems, conducted from 1997 to 2001. We tested HIV-RNA levels and administered a standardized questionnaire regarding demographics, substance use, receipt of ART, and adherence with ART, every 6 months for up to 7 occasions. Among the 235 subjects on ART, we investigated the relationship between literacy and 2 outcomes: 100% 3-day self-reported adherence and HIV-RNA suppression (<500 copies). RESULTS: Subjects' literacy levels were the following: 14% < or = 6th grade, 29% 7th to 8th grade, and 57% > or = 9th grade. In 66% of the observations (478/725), subjects reported 100% 3-day adherence with ART. Of the 685 HIV-RNA assays from these subjects, 62% had <500 copies. In unadjusted analyses, subjects with the lowest literacy level (< or = 6th grade) had a higher odds of adherence (odds ratio [OR] 2.23, 95% confidence interval 1.15 to 4.30) and HIV-RNA suppression (OR 2.01, 95% confidence interval 1.03 to 3.90) compared with those with > or = 9th grade literacy. This trend persisted but was no longer statistically significant in adjusted models of adherence (AOR 1.93, 95% confidence interval 0.86 to 4.31) and HIV-RNA suppression (AOR 1.70, 95% confidence interval 0.79 to 3.65). CONCLUSION: Contrary to our hypothesis, low literacy was not associated with a lower odds of adherence or virologic suppression in this longitudinal analysis of HIV-infected patients with a history of alcohol problems. Indeed, trends in these data suggest the possibility that low literacy may be associated with a higher odds of adherence and virologic suppression. These counterintuitive findings underscore the need to pursue a fuller understanding of the mechanisms by which literacy affects health outcomes.

Adult↗
PubMed2001

The urine protein to creatinine ratio (P/C) as a predictor of 24-hour urine protein excretion in renal transplant patients.

BACKGROUND: The purpose of this study was to examine the utility of the random urine protein to creatinine ratio (P/C) in evaluation and longitudinal management of proteinuria in adult renal transplant recipients with or without overt nephropathy in an outpatient clinic. METHODS: A total of 289 adult renal transplant recipients provided 24-hr urine collections for total protein and creatinine, followed by a random urine for protein and creatinine. For longitudinal analysis, 192 of these patients provided two 24-hr urine collections with concomitant random urine specimens separated on average by 6.8 months. As well, 134 patients provided a total of 851 multiple-paired spot and 24-hr urine samples (range 2 to 12) over a 2-year period. RESULTS: The log random urine P/C ratio correlated significantly to the log 24 UP (r=0.749, P<0.0001) with or without nephrotic range proteinuria. High sensitivity (74.4-90%) and specificity values (93-98%) were found for estimating proteinuria from 0.5 to 2 g/day. However, the precision of estimation decreased as the level of urinary protein excretion increased to >3 g/day. The positive predictive value decreased as proteinuria became >3 g/day, perhaps because of the low prevalence of patients with high level proteinuria in our sample. The direction of change in P/C ratio longitudinally was accompanied by a similar direction of change in 24 UP, which was highly significant (r=0.7555, P<0.0001). CONCLUSION: We conclude that the urine P/C ratio is a useful and convenient screening and longitudinal test for proteinuria.

Adolescent↗
PubMed2007

Smoking and injury in Royal Marines' training.

BACKGROUND: Training for the Royal Marines (RMs) is considered to be one of the most arduous military training regimes in the world. Approximately 16% of the annual intake of recruits suffer an injury. Smoking has been found to be a predisposition to injury. OBJECTIVE: To examine the relationship between recruits' smoking status on entry to training and subsequent incidence of injury. METHOD: Retrospective, longitudinal analysis of 1 year's intake of RM recruits at Commando Training Centre Royal Marines. RESULTS: A significantly greater proportion of RM recruits who were smokers on entry to training experienced a physical injury during the course than their non-smoking counterparts (chi-square = 8.15, P < 0.01). A recruit who smoked on entry to training was almost twice as likely to acquire an injury during training [relative risk = 1.7 (95% CI = 1.2-2.8)]. CONCLUSION: Smoking status of RM recruits in training was significantly associated with injury.

Adult↗
PubMed1993

Soluble interleukin-2 receptor and urinary neopterin concentrations in malignant lymphoma.

The serum concentrations of soluble interleukin-2 receptors and urine neopterin were studied in 82 patients with malignant lymphomas (25 patients with Hodgkin's disease and 57 patients with non-Hodgkin's lymphoma. Increases in soluble interleukin-2 receptors and in urinary neopterin were significantly correlated with the clinical phase of the disease. The average values in both Hodgkin's disease and non-Hodgkin's lymphoma patients suffering from the disease in its active phase were significantly higher than those of patients in complete remission. Neopterin concentrations (but not soluble interleukin-2 receptor concentrations) were also elevated in clinical stages III-IV of each disease. Urinary neopterin correlated directly and significantly with the erythrocyte sedimentation rate and inversely with haemoglobin. Finally, a longitudinal analysis showed a general tendency for the markers to return to normal values, in accordance with the favourable outcome of therapy; this was more evident for urinary neopterin than for soluble interleukin-2 receptors. These findings seem to confirm that soluble interleukin-2 receptors and especially urinary neopterin can be useful markers for monitoring and prognosis of malignant lymphomas.

Adult↗
PubMed2006

Clonality analysis by sequence variation of the latent membrane protein 1 gene in patients with chronic active Epstein-Barr virus infection.

Chronic active Epstein-Barr virus (EBV) infection is a severe systemic disease associated with high rates of mortality and morbidity. Recent studies suggest that the clonal expansion of EBV-infected T or natural killer cells plays a crucial role in the pathogenesis of chronic active EBV infection. However, it is not clear whether chronic active EBV infection is truly a monoclonal disorder that originates from one cell. The clonality of EBV was investigated by sequence variation of the latent membrane protein 1 (LMP1) gene, which has a high degree of sequence heterogeneity. Peripheral blood mononuclear cells were obtained from nine Japanese patients with chronic active EBV infection and four with infectious mononucleosis. A carboxyl-terminal region of the LMP1 gene was analyzed by polymerase chain reaction (PCR). The amplified PCR products were subcloned, and 18 clones from each sample were sequenced. Patients with chronic active EBV infection each had two to five different LMP1 nucleotide sequences, whereas patients with infectious mononucleosis each had one to seven different sequences. Patients with chronic active EBV infection and infectious mononucleosis both had one dominant sequence. Longitudinal analysis was performed in four patients with chronic active EBV infection, in whom the dominant strains were found to have remained unchanged for several years. The results suggest that EBV in patients with chronic active EBV infection was polyclonal, although clonal expansion may occur. Collectively, these findings are critical to clarify further the pathogenesis of chronic active EBV infection and aid in the development of effective treatment strategies.

Adolescent↗
PubMed2026

Circulating IGF2BP3 enables risk stratification and predicts treatment response in Ewing sarcoma.

Ewing sarcoma (EWS), the second most common pediatric bone tumor, presents with a markedly heterogeneous clinical spectrum and optimal risk stratification is therefore crucial for improving treatment outcomes. The RNA-binding protein IGF2BP3 is a critical oncogenic driver of EWS malignancy. This study evaluates the clinical utility of circulating IGF2BP3 as a biomarker to predict treatment response and risk of disease progression in patients with EWS. Plasma samples from 60 patients with EWS diagnosed and treated at the IRCCS Rizzoli Orthopedic Institute (Bologna, Italy) were collected at diagnosis before treatment initiation and/or after induction chemotherapy. For 51 of these patients, blood was collected at diagnosis, prior to any treatments. For 25 patients, blood samples were available at diagnosis and before surgical intervention, allowing longitudinal analysis in the same patient. For 9 patients, blood was collected only after preoperative chemotherapy, before surgical intervention. Circulating IGF2BP3 levels were quantified using a highly specific and sensitive ELISA assay. Plasma samples from healthy donors served as controls. IGF2BP3 plasma levels were correlated with IGF2BP3 tumor tissue expression, established clinical risk factors, and cumulative incidence of relapse using univariable and multivariable analyses. Plasma IGF2BP3 levels were significantly elevated in patients with EWS compared with healthy controls, with a subset of patients (22/51, 43.2%) exhibiting clinically relevant concentrations. Circulating IGF2BP3 levels reflected tumor expression of the molecule and provided additional prognostic information beyond standard clinicopathologic features. The prognostic impact of circulating IGF2BP3 was primarily observed in patients with localized disease, in whom elevated levels were identified as a significant adverse prognostic factor for disease-specific survival (hazard ratio, 10.63; 95% CI, 1.27-88.62; P = 0.029). Longitudinal monitoring demonstrated that persistence of IGF2BP3 in plasma after induction chemotherapy was a strong predictor of poor clinical outcomes. Circulating IGF2BP3 represents a valuable biomarker for early risk stratification in EWS, particularly in patients with localized disease. Although this is single-marker assay, the expression of the molecule may impact on the fate of many mRNAs. We present an accurate, simple, cost-effective and easy clinical applicable tool to support risk-adapted therapeutic interventions. The limited number of employed patients warrants the need of larger cohorts for validation.

Humans↗
PubMedDate not supplied

Drinking patterns among Swedish women: results from a 5-year follow-up of a population-based study.

The aims of this study were to: (1) document women's alcohol use over a 5-year period; (2) compare different measures of alcohol consumption such as high alcohol consumption (HAC) and high episodic drinking (HED); (3) to follow the incidence and course of alcohol dependence and abuse (ADA). The study is part of a longitudinal general population-based study, Women and Alcohol in Göteborg. From a stratified random sample of 479 respondents, 399 were interviewed in the first wave (1989/90). In the second wave (1995/96), 386 of the 479 women were available for a follow-up interview. The 12-month prevalence of ADA was 1.3% in both waves. In the longitudinal analysis the 5-year cumulative incidence of ADA was 0.1%. Two new cases of ADA were found. The prevalence of HAC and HED decreased in women of all ages except HED in women born in 1955. We conclude that the 12-month prevalence of ADA remained the same at the 5-year follow-up and that, in contrast to what has been found in some other studies, there was an overall decrease in HAC and in HED.

Adult↗