Aggressive gastric carcinoma producing alpha-fetoprotein: a case report and review of the literature.

A 65-year-old man presented to our hospital with abdominal pain, dyspepsia and anorexia. Laboratory tests showed an altered liver function and abdomen ultrasonography revealed multiple liver nodules, suspected to be metastatic lesions. Serous tumor markers were elevated and a very high level of alpha-fetoprotein was found. Computer tomography confirmed the hepatic lesions and disclosed a thickening of the lesser curvature of the gastric wall. A subsequent endoscopy showed an ulcer on the lesser curvature. Biopsies taken from the gastric ulcer and the liver nodule revealed an adenocarcinoma, both of gastric origin. Shortly after the diagnosis, the patient's condition worsened and he died only 15 days later. This case report illustrates how alpha-fetoprotein-producing gastric adenocarcinomas have a high incidence of venous and lymphatic invasion and a rapid hepatic spread with a very poor prognosis

Non-invasive assessment of fibrosis in non-alcoholic fatty liver disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries, and its prevalence is increasing worldwide. It currently affects approximately 30% of adults and 10% of children and adolescents. The resulting increase in the number of patients with NAFLD is expected to translate into increased numbers of patients with liver cirrhosis, and hepatocellular carcinoma. In this context, it is particularly important to identify patients at risk for progressive chronic liver disease. Currently, liver biopsy is the gold standard to diagnose non-alcoholic steatohepatitis (NASH) and to establish the presence and stage of fibrosis. Due to the remarkable increase in the prevalence of NAFLD and the concomitant efforts in developing novel therapies for patients with NASH, non-invasive, simple, reproducible, and reliable noninvasive methodologies are needed. This paper provides a concise overview of the role of non-invasive diagnostic tools for the determination of presence and extent of fibrosis in NAFLD patients, with particular emphasis on the methods currently available in clinical practice

Effects of cardiac resynchronization therapy on systemic inflammation and neurohormonal pathways in heart failure

Background: The effect of cardiac resynchronization therapy (CRT) on systemic inflammation and neurohormonal alterations associated with heart failure is not well characterized. Accordingly, we aimed to assess the long term effects of CRT on systemic inflammation and neurohormonal factors in heart failure patients. Methods and results: In 47 HF patients (NYHA III–IV) we evaluated, at baseline and after one year of CRT: TNF-α, TNF soluble receptors (sTNFR1 and sTNFR2), insulin-like growth factor-1α (IGF-1α), adiponectin, norepinephrine, pro-atrial natriuretic peptide (pro-ANP), N-terminal-pro-brain natriuretic peptide (NT-proBNP) and angiotensin II, NYHA functional class, quality of life (the Minnesota Living with Heart Failure questionnaire), a 6-minute walk test and an echocardiogram. Long-term CRT decreased activation of renin–angiotensin system (RAS) only in patients with reverse remodelling. It failed to prevent a decline in adiponectin levels, regardless of reverse remodelling. NT-proBNP remained unchanged in patients with reverse remodelling, whereas its levels increased in those without reverse remodelling. IGF-1α increased with CRT, whereas CRT had no effect on pro-ANP and inflammatory markers. Conclusions: Long-term CRT is associated with decreased RAS activation and stabilization of NT-proBNP in heart failure patients with reverse remodelling. Long-term CRT, with or without reverse remodelling, does not affect systemic inflammation and fails to prevent a decline in adiponectin

Aging related changes of circadian rhythmicity of cytotoxic lymphocyte subpopulations

<p>Abstract</p> <p>Background</p> <p>Immunosenescence is a process that affects all cell compartments of the immune system and the contribution of the immune system to healthy aging and longevity is still an open question. Lymphocyte subpopulations present different patterns of circadian variation and in the elderly alteration of circadian rhythmicity has been evidenced. The aim of our study was to analyze the dynamics of variation of specific cytotoxic lymphocyte subsets in old aged subjects.</p> <p>Methods</p> <p>Lymphocyte subpopulation analyses were performed and cortisol serum levels were measured on blood samples collected every four hours for 24 hours from fifteen healthy male young-middle aged subjects (age range 36-55 years) and fifteen healthy male old aged subjects (age range 67-79 years).</p> <p>Results</p> <p>In healthy young-middle aged subjects CD20 were higher and at 06:00 h CD8+ dim correlated positively with CD16+ and positively with γδTCR+ cells, CD16 correlated positively with γδTCR+ cells At 18:00 h CD8+ dim correlated positively with CD16+ and positively with γδTCR+ cells, CD16+ correlated positively with γδTCR+ cells and a clear circadian rhythm was validated for the time-qualified changes of CD3+, CD4+, CD20+, CD25+ and HLA-DR+ cells with acrophase during the night and for the time-qualified changes of CD8+, CD8+ bright, CD8+ dim, CD16+ and γδTCR+ cells with acrophase during the day. In old aged subjects CD25, DR+ T cells and cortisol serum levels were higher, but there was no statistically significant correlation among lymphocyte subpopulations and a clear circadian rhythm was evidenced for time-qualified changes of CD3+ and CD25+ cells with acrophase during the night and for the time-qualified changes of CD8+ cells and cortisol with acrophase during the day.</p> <p>Conclusion</p> <p>Our study has evidenced aging-related changes of correlation and circadian rhythmicity of variation of cytotoxic lymphocyte subpopulations that might play a role in the alteration of immune system function in the elderly.</p

Immune system alterations in lung cancer patients.

The immune system plays an important role in the defense against neoplastic disease and immune responses show temporal changes related to circadian variations of antibodies, total lymphocytes in the peripheral blood and cell mediated immune responses. In this study we evaluate, lymphocyte subpopulations and interleukin-2 (IL-2) serum levels in peripheral blood samples collected at four-hour intervals for 24-hours starting at 06.00h from ten healthy subjects aged 65–79 years (mean age ± S.E. 67.28 ±3.11) and from ten subjects suffering from untreated non small cell lung cancer aged 65–78 years (mean age ± S.E. 68.57 ± 1.81). Areas under the curve, mean diurnal levels (mean of 06.00–10.00–14.00 h) and mean nocturnal levels (mean of 18.00–22.00–02.00 h) were calculated, and the presence of circadian rhythmicity was evaluate. When we compared AUC values there was a decrease in CD8bright (T suppressor subset) and an increase in CD16 (natural killer cells) and of IL-2 serum levels in cancer patients. When we compared mean diurnal levels, CD8 (T suppressor/cytotoxic subset) and CD8bright levels were lower, and CD16 levels were higher in cancer patients. When we compared mean nocturnal levels, CD16 and CD25 (T and B activated lymphocytes with expression of the a chain of IL-2 receptor) levels were higher, while CD8, CD8bright, CD20 (total B-cells), TcRd1 (epitope of the constant domain of d chain of T-cell receptor 1) and dTcS1 (epitope of the variable domain of d chain of T-cell receptor1) levels were lower in cancer patients. A clear circadian rhythm was validated for the time-qualified changes in CD4, CD20, HLA-DR with acrophase at night, and CD8, CD8bright, CD8dim, CD16, TcRd1 and dTcS1 with acrophase in the morning in the control group. A clear circadian rhythm was validated for the time-qualified changes in CD4 with acrophase at night, in the group of cancer patients. Results obtained in our study show that lung cancer is associated with anomalies of proportion and circadian variations of lymphocyte subsets that must be considered when adoptive immunotherapy has to be planned

Transdisciplinary unifying implications of circadian findings in the 1950s

A few puzzles relating to a small fraction of my endeavors in the 1950s are summarized herein, with answers to a few questions of the Editor-in-Chief, to suggest that the rules of variability in time complement the rules of genetics as a biological variability in space. I advocate to replace truisms such as a relative constancy or homeostasis, that have served bioscience very well for very long. They were never intended, however, to lower a curtain of ignorance over everyday physiology. In raising these curtains, we unveil a range of dynamics, resolvable in the data collection and as-one-goes analysis by computers built into smaller and smaller devices, for a continued self-surveillance of the normal and for an individualized detection of the abnormal. The current medical art based on spotchecks interpreted by reference to a time-unqualified normal range can become a science of time series with tests relating to the individual in inferential statistical terms. This is already doable for the case of blood pressure, but eventually should become possible for many other variables interpreted today only based on the quicksand of clinical trials on groups. These ignore individual differences and hence the individual's needs. Chronomics (mapping time structures) with the major aim of quantifying normalcy by dynamic reference values for detecting earliest risk elevation, also yields the dividend of allowing molecular biology to focus on the normal as well as on the grossly abnormal

Time related variations in stem cell harvesting of umbilical cord blood

Umbilical cord blood (UCB) contains hematopoietic stem cells and multipotent mesenchymal cells useful for treatment in malignant/nonmalignant hematologic-immunologic diseases and regenerative medicine. Transplantation outcome is correlated with cord blood volume (CBV), number of total nucleated cells (TNC), CD34+ progenitor cells and colony forming units in UCB donations. Several studies have addressed the role of maternal/neonatal factors associated with the hematopoietic reconstruction potential of UCB, including: gestational age, maternal parity, newborn sex and birth weight, placental weight, labor duration and mode of delivery. Few data exist regarding as to how time influences UCB collection and banking patterns. We retrospectively analyzed 17.936 cord blood donations collected from 1999 to 2011 from Tuscany and Apulia Cord Blood Banks. Results from generalized multivariable linear mixed models showed that CBV, TNC and CD34+ cell were associated with known obstetric and neonatal parameters and showed rhythmic patterns in different time domains and frequency ranges. The present findings confirm that volume, total nucleated cells and stem cells of the UCB donations are hallmarked by rhythmic patterns in different time domains and frequency ranges and suggest that temporal rhythms in addition to known obstetric and neonatal parameters influence CBV, TNC and CD34+ cell content in UBC units

Chronobiologic study of the GH-IGF1 axis and the ageing immune system

One of the many systems that weakens as we age is our immune system and there is a reduction in the GH-IGF1 axis activity with increasing age. In this study we evaluated the immune system and the GH-IGF1 axis function in healthy ageing. CD3, CD4, CD20, CD25, HLA-DR and GH showed acrophase during the night, whereas CD8, CD16 and TCRγδ expressing cells showed acrophase during the day. MESOR of CD3 was higher in the old aged subjects, MESOR of CD20 and CD20 values at 14:00h and at 02:00h were higher in the young middle aged subjects, MESOR of CD25 and CD25 values at 10:00 were higher in the elderly subjects, MESOR of HLA-DR was higher in the young middle aged subjects, whereas MESOR of DR+T cells and HLA-DR at 02:00h were higher in the elderly subjects, MESOR of TCRγδ bearing cells was higher in the elderly subjects, GH value at 18:00h was also higher in the elderly subjects, and MESOR of IGF1 was higher in the young middle aged subjects. There was a statistically significant difference for the acrophases of CD25, HLA-DR and IGF1. There were different and opposing correlations among lymphocyte subpopulations and GH-IGF1 axis hormones in young and middle aged subjects in comparison with old aged subjects. Linear regression evidenced a statistically significant positive trend between age and the 24h mean of CD3 and CD25 and a statistically significant negative trend between age and the 24h mean of CD20 and GH. In conclusion, ageing is associated with an altered GH and IGF1 secretion, with decreased peripheral B cell compartment, increased peripheral T cell compartment and alterations of circadian rhythmicity

Seasonal pattern of peptic ulcer hospitalizations: analysis of the hospital discharge data of the Emilia-Romagna region of Italy

BACKGROUND: Previous studies have reported seasonal variation in peptic ulcer disease (PUD), but few large-scale, population-based studies have been conducted. METHODS: To verify whether a seasonal variation in cases of PUD (either complicated or not complicated) requiring acute hospitalization exists, we assessed the database of hospital admissions of the region Emilia Romagna (RER), Italy, obtained from the Center for Health Statistics, between January 1998 and December 2005. Admissions were categorized by sex, age ( or = 75 yrs), site of PUD lesion (stomach or duodenum), main complication (hemorrhage or perforation), and final outcome (intended as fatal outcome: in-hospital death; nonfatal outcome: patient discharged alive). Temporal patterns in PUD admissions were assessed in two ways, considering a) total counts per single month and season, and b) prevalence proportion, such as the monthly prevalence of PUD admissions divided by the monthly prevalence of total hospital admissions, to assess if the temporal patterns in the raw data might be the consequence of seasonal and annual variations in hospital admissions per se in the region. For statistical analysis, the chi2 test for goodness of fit and inferential chronobiologic method (Cosinor and partial Fourier series) were used. RESULTS: Of the total sample of PUD patients (26,848 [16,795 males, age 65 +/- 16 yrs; 10,053 females, age 72 +/- 15 yrs, p or = 75 yrs of age. There were more cases of duodenal (DU). (89.8%) than gastric ulcer (GU) (3.6%), and there were 1,290 (4.8%) fatal events. Data by season showed a statistically difference with the lowest proportion of PUD hospital admissions in summer (23.3%) (p < 0.001), for total cases and rather all subgroups. Chronobiological analysis identified three major peaks of PUD hospitalizations (September-October, January-February, and April-May) for the whole sample (p = 0.035), and several subgroups, with nadir in July. Finally, analysis of the monthly prevalence proportions yielded a significant (p = 0.025) biphasic pattern with a main peak in August-September-October, and a secondary one in January-February. CONCLUSIONS: A seasonal variation in PUD hospitalization, characterized by three peaks of higher incidence (Autumn, Winter, and Spring) is observed. When data corrected by monthly admission proportions are analyzed, late summer-autumn and winter are confirmed as higher risk periods. The underlying pathophysiologic mechanisms are unknown, and need further studies. In subjects at higher risk, certain periods of the year could deserve an appropriate pharmacological protection to reduce the risk of PUD hospitalization