European Projects for Patients with Dementia and Their Caregivers.

As we all know there is no treatment that can stop or delay the progression of dementia. The treatment we use is only symptomatic. EFNS (European Federation of Neurological Societies) recommendations for dementia prevention by Sorbi et al. (2012) concluded that there is no treatment, no lifestyle, which could have an effect on prevention or delay of onset of different forms of dementia until today. The future studies in prevention must recruit younger people, larger sample, and for longer period. The last 10 years we have run, in collaboration with organizations in different European countries, many projects in order to support patients with neurodegenerative diseases, mainly patients with dementia and their caregivers. The first project was a 2-year prospective cohort study of antidementia drug non-persistency in mild-to-moderate Alzheimer's disease (AD) in Europe: predictors of discontinuation and switch in the ICTUS (Impact of Cholinergic Treatment USe) study, an FP5 project with 1380 patients. Five studies were published. The second project was DESCRIPA study, an FP5 project to DEvelopment of Screening guidelines and clinical CRIteria for Predementia Alzheimer's disease, with 881 patients with mild cognitive impairment (MCI). LLM (Long Lasting Memories) and VRADA (A virtual reality application for the exercise of dementia and Alzheimer patients) are two projects that include body and cognitive exercise for health for the elderly and patients with mild cognitive impairment. The next is the RECAGE (REspectful Caring for the AGitated Elderly) project (Horizon 2020), a prospective cohort study for coping with behavioral and psychological symptoms of dementia. With six European universities we finished a very interesting FP6 project, the AddNeuroMed one, which gives even now information about the progression of normal elderly MCI and AD patients, in collaboration with other consortia. A very interesting Innovative Medicines Initiative (IMI) project about digital biomarkers was entitled Remote Assessment of Disease and Relapse-Alzheimer's Disease (RADAR project). The main goal of this project was the development and validation of technology-enabled, quantitative and sensitive measures of functional decline in people with early-stage AD. A running project is an Erasmus+ one in the higher education field, "Genetic counseling in European universities: The case of neurodegenerative diseases" (GECONEU project). The target of this study is to develop an online course for university students focusing on genetic counseling, and support people and society to better understand the aims of genetic testing and the usefulness of genetic counseling by involving students in an innovative learning and teaching setting. AD-gaming, BRIDGE, iCONNECT (Intergenerational CONtact between studeNts and people with dEmentia through CreaTive education), E.L.So.M.C.I (English Lessons with the Use of Songs for People with Mild Cognitive Impairment), Games4CoSkills, and De-Sign are all Erasmus+ projects that aim to improve the quality of life of patients with MCI or dementia. Story2remember, Dementia right, ASPAD (Augmentation of the Support of Patients suffering from Alzheimer's Disease and their caregivers), INFOCARE (Supporting Informal Caregivers of People with Dementia), S.IN.CA.L.A (Supporting Informal Carers: A Whole-Family and Life course Approach), and PIA (Peer support workers as an Innovative force in Advocacy in dementia care) are all Erasmus+ projects for training and supporting caregivers of patients with dementia.

A Novel Method of Teaching English to People with Mild Cognitive Impairment Using Songs: A Randomized Controlled Trial Protocol.

BACKGROUND: People with mild cognitive impairment (MCI) need to prevent the further decline of their cognitive functions, and one way to do so is by learning a foreign language. OBJECTIVE: This study describes the development of a protocol for a novel, non-pharmacological intervention for people with MCI that seeks to prevent or reduce cognitive decline by teaching English through songs. METHODS: The development of this protocol follows a mixed-methodology approach, consisting of three stages: 1) development of the protocol of the intervention, 2) a randomized controlled trial study with two arms over six months that includes an intervention group and a control group, and 3) the evaluation of the protocol by trainers. In the second stage, we recruited a total of 128 people with MCI from the five participating countries of this study (Greece, Spain, Croatia, Slovenia, and Italy). This educational program will assess three main outcomes after 6 months of the English Lessons with the Use of Songs for People with Mild Cognitive Impairment (E.L.So.M.C.I.) workshops. RESULTS: Our primary outcome will hopefully be an improvement in general cognition in the intervention group compared to the control group from baseline to 6 months follow-up. Secondary outcomes include a decrease in participants' anxiety and depression and an improvement in their quality of life. Development of English language skills is the last outcome.

Transcriptional suppression of BACH2 by the Bcr-Abl oncoprotein is mediated by PAX5.

Bach2 is a lymphoid-specific transcription factor with a prominent role in B-cell development and apoptosis-induction in response to oxidative stress. We previously showed that Bach2 is downregulated in chronic myeloid leukaemia (CML), and here we demonstrate the mechanism by which Bcr-Abl mediates this phenomenon. We have cloned a 3.9 Kb genomic DNA fragment upstream of the transcription initiation site, and delineated the core and proximal BACH2 promoter regions. Transient BCR-ABL expression led to significant reduction in BACH2 promoter activity and this effect was dependent on the kinase function of the oncoprotein. Sequential deletions disclosed several regulatory elements within the promoter region, as well as within BACH2 exonic sequences. Analysis of these elements and transient transfection assays led to the identification of the Pax5 transcription factor as a potent trans-activator of BACH2, whose effect is predominantly mediated through occupation of a binding site on the BACH2 promoter, as demonstrated by both in vitro and in vivo experiments. Overall, our data show that Pax5 functions as an intermediate effector in the Bcr-Abl-mediated transcriptional repression of BACH2. The current results, combined with previous reports, establish Pax5 and Bach2 as transcriptional targets of Bcr-Abl, whose downregulation may contribute to lymphoid blast crisis of CML.

Serum adiponectin levels in different types of non alcoholic liver disease. Correlation with steatosis, necroinflammation and fibrosis.

BACKGROUND AND STUDY AIMS: In recent studies adiponectin has been implicated in the pathogenesis of non alcoholic liver disease (NAFLD), a common chronic liver disease with a broad spectrum of histopathologic findings. The aim of this study was to investigate the correlation between serum adiponectin levels and steatosis, necroinflammation and fibrosis in different types of NAFLD patients. PATIENTS AND METHODS: Forty three patients with elevated liver enzymes and biopsy proven non alcoholic fatty liver disease and 38 patients with clinically diagnosed NAFLD and permanently normal liver enzymes were prospectively enrolled in the study. Patients with biopsy proven NAFLD were divided into two groups: non alcoholic steatohepatitis (NASH): 25 patients and simple steatosis: 18 patients. Serum adiponectin levels were measured with an ELISA immunoassay, and BMI, fasting serum glucose, total and HDL cholesterol, fasting triglyceride levels and insulin resistance were determined. RESULTS: Groups did not differ in age, sex, BMI, waist circumference and HOMA - IR. Only patients with confirmed NASH had lower serum adiponectin levels in comparison to NAFLD patients with both abnormal (6.6 +/- 4.7 microg/mL vs 10.8 +/- 5.6 microg/mL, p = 0.01) as well as normal liver enzymes (6.6 +/- 4.7 microg/mL vs 9.2 +/- 4.8 microg/mL, p = 0.01). For the whole NAFLD group with elevated liver enzymes no correlation was found between serum adiponectin levels and the degree of liver steatosis or fibrosis stage. Also no correlation was found between adiponectin levels and BMI, ALT, AST, gamma GT or HOMA-IR. CONCLUSIONS: Patients with established NASH have lower serum adiponectin levels than NAFLD patients with normal or abnormal liver enzymes. Adiponectin was not associated with the severity of hepatic fibrosis.

Serum adiponectin in chronic hepatitis C and B.

Adiponectin possesses anti-inflammatory, insulin-sensitizing and anti-atherosclerotic properties. The aim of this study was to assess the levels of serum adiponectin in patients with chronic viral hepatitis C and B and correlate them with parameters exploring insulin resistance and indices of chronic liver disease. Seventy-two patients with chronic hepatitis C virus (HCV) infection and 73 patients with chronic hepatitis B virus (HBV) infection, matched for age and sex, were studied. All individuals were examined for serum concentrations of adiponectin, insulin, C-peptide and homeostasis model assessment for insulin resistance (HOMA-IR). Viral parameters and liver histology were also evaluated. Serum adiponectin levels were significantly higher in HCV compared with HBV-infected patients. Correlation analysis in the whole group demonstrated that serum adiponectin was positively correlated with aspartate aminotransferase, alkaline phosphatase, globulins, high-density lipoprotein cholesterol and staging score, while it was negatively correlated with body mass index, insulin, C-peptide and HOMA-IR. Logistic regression analysis identified type of infection (HCV vs HBV), alcohol consumption more than 25 g daily, serum total globulin and low C-peptide as significant predictive variables associated with high adiponectin levels. Higher levels of serum adiponectin in HCV compared with HBV patients could have a role in the slower disease progression of chronic HCV infection. In addition, alcohol intake more than 25 g daily seems to be a significant predictor for hyperadiponectinaemia in patients with chronic viral hepatitis C or B. Finally, in this study, a clear positive association between adiponectin and hepatic necroinflammation or staging score was not found.

Improvement of iodine deficiency after iodine supplementation in schoolchildren of Azerbaijan was accompanied by hypo and hyperthyrotropinemia and increased title of thyroid autoantibodies.

OBJECTIVE: In the mountainous areas of Azerbaijan the schoolchildren suffer from severe Iodine Deficiency (ID) with median Urinary iodine excretion (UIE) 36 mcg/l and prevalence of goiter 99% (estimated by US). In a population of 293,000 schoolchildren aged 8-14 y.o. we administered capsules containing 190 mg of iodized oil (Lipiodol-Guerbet, Cedex, France) twice yearly in 6 months apart (total 380 mg). The aim of the present study was to evaluate the efficacy, the benefits, as well as the possible side-effects in a follow-up period of 6 and 12 months after the initial administration of iodized oil. METHODS: Six and 12 months after the initial administration of iodide, two representative samples of 391 and 326 children respectively were examined. The evaluation included: estimation of goiter by US, determination of UIE and serum measurements of T3, T4, TSH, Tg, autoantibodies against thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg). RESULTS: There was an improvement in median UIE which increased from 36 mcg/l to 68 and 81 mcg/l after 6 and 12 months of treatment respectively. The prevalence of goiter decreased from 99% to 54% and 26% respectively. Tg was decreased at 6 and 12 months from the first administration, whereas TSH remained unchanged at 6 months and decreased at 12 months when compared to the latter value. Hypothyroidism was detected in 7% of children after iodide administration both at 6 and 12 months, but overt hypothyroidism was observed only in 0.5% at 12 months. Subclinical hyperthyroidism was detected in 2% and 6% after iodide administration both at 6 and 12 months. There was a significant increase in the title of thyroid auto antibodies in 6 months which was retained and increased in 12 months. There was no relation between the appearance of thyroid dysfunction and the positive thyroid auto antibodies. CONCLUSION: The dose of 190 mg iodide administered twice yearly, improved iodine deficiency and endemic goiter in schoolchildren. The increase of UIE resulted from iodide administration, was accompanied by an increased title of thyroid auto-antibodies and an increased prevalence of hyper- and hypothyrotropinemia apparently of no autoimmune etiology.

Dissociation of the early decline in serum T(3) concentration and serum IL-6 rise and TNFalpha in nonthyroidal illness syndrome induced by abdominal surgery.

The etiology of the prompt decline in serum T(3) in patients with nonthyroidal illness syndrome has not been adequately explained. It has been attributed to various parameters, including test artifacts, inhibitors of T(4) and T(3) binding to proteins, decreased 5'-deiodinase activity, and circulating cytokines. Currently, much attention is centered on the role of IL-6 and TNFalpha in developing the nonthyroidal illness syndrome through an effect on the hypothalamus, pituitary, and possibly 5'-deiodinase activity. We therefore studied the relation of the endogenous serum IL-6 and TNFalpha rise early in the course of nonthyroidal illness syndrome to the early decline in serum T(3) in 19 apparently healthy individuals, aged 43 +/- 16 yr, who underwent elective abdominal surgery for cholelithiasis or gastroplasty. Serum T(3), free T(3), T(4), free T(4), rT(3), TSH, IL-6, and TNFalpha were measured before and at various time intervals up to 42 h after skin incision. We observed a prompt decline in serum T(3) 30 min before skin incision, which continued to decline throughout the observational period. The magnitude of the decline reached 20% from the baseline value at 2 h. The early decline of T(3) was attenuated and lasted from the 2-8 h, probably due to the sharp increase in serum TSH that started immediately after the entrance to the operating room and lasted for 2 h. In contrast, serum T(4) and free T(4) concentrations were increased soon after skin incision and remained elevated during the first postoperative day. Serum rT(3) increased approximately 6 h after the initiation of surgery and remained elevated thereafter. Serum IL-6 remained essentially undetectable for 2 h after skin incision, whereas serum T(3) was low. Two hours after skin incision, serum IL-6 increased sharply and remained elevated throughout the observational period. Serum TNFalpha remained essentially undetectable throughout the postoperative period. Serum cortisol increased rapidly upon entrance to the operating room and remained elevated throughout the postoperative period. We conclude that the decline in serum T(3) early in the course of nonthyroidal illness syndrome is not due to increased serum IL-6 or TNFalpha levels. The brisk TSH secretion soon after the onset of the syndrome attenuates the decline in serum T(3) due to T(3) secretion from the thyroid. The early and brisk cortisol response to surgery may at least in part explain the early decrease in serum T(3) in nonthyroidal illness syndrome.

Iodine deficiency in Azerbaijan after the discontinuation of an iodine prophylaxis program: reassessment of iodine intake and goiter prevalence in schoolchildren.

The goal of this study was to assess the prevalence of iodine deficiency (ID) in Azerbaijan after the discontinuation of an iodine prophylaxis program by assessing the prevalence of goiter, iodine intake, and thyroid function. The study included 942 schoolchildren (475 boys and 467 girls) ages 8-14 years, from 13 distinct regions. The survey included the following: (1) clinical evaluation; (2) assessment of thyroid volume both by ultrasound and by palpation; (3) determination of iodide in a morning urine specimen using the classic Sandel-Kolthoff reaction in 347 schoolchildren; (4) determinations of thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4), thyroglobulin (Tg), and anti-thyroid peroxidase (TPO) in serum (n = 165) and TSH in whole blood spotted on filter paper (n = 942). The prevalence of goiter for the whole country was determined by ultrasound (US) to be 86% and by palpation 66%, reaching 100% in the mountainous regions of Caucasus. The median urinary iodine excretion (UIE) was 54 microg/L, reaching level of 26 and 39 microg/L in the Caucasus region. In conclusion, according to the World Health Organization (WHO) classification, Azerbaijan now has mild to moderate ID (median UIE, 54 microg/L) and in the mountainous regions with severe ID. The high prevalence of goiter and the low UIE emphasizes the need for urgent medical reintervention. An iodination program is now implemented by our team in the mountainous regions under the auspice of the government of Azerbaijan.

Thyroid function and immune profile in rheumatoid arthritis. A controlled study.

The aim of our study was to determine the prevalence of thyroid dysfunction and autoimmune abnormalities in rheumatoid arthritis (RA) and to further investigate the possible association between D-penicillamine and autoimmune thyroiditis. For this purpose, one hundred and one unselected consecutive patients with RA and 70 age and sex matched controls were studied prospectively. Evaluation included a complete history and physical examination with special attention to symptoms suggestive of thyroid pathology, routine laboratory and serologic immune profile, plus determination of serum levels of thyroxine (T4), triiodothyronine (T3), thyroid stimulating hormone (TSH), antibodies to thyroid peroxidase (AbTPO) and TSH receptor antibodies (TRAB). Serum thyroxine binding globulin (TBG) was measured in all subjects with high thyroid hormone levels, whereas free T3 and T4 concentrations were determined in all individuals with abnormal T3, T4, TSH or TBG. Six patients with hyperhyroidism, 3 with hypothyroidism and 1 with the euthyroid hyperthyroxinemia (EH) syndrome were found, whereas four of the controls had hyperthyroidism. Thirteen patients and 6 controls had high AbTPO levels whereas no one had high TRAB. No association was detected between thyroid abnormalities and any serologic RA finding. Furthermore, no correlation between thyroid dysfunction and elevated AbTPO's was found. A relatively high prevalence of thyroid dysfunction (9,9%) and subclinical autoimmune thyroiditis (12,9%), the latter indicated by elevated AbTPO's, was found in our RA patients. These figures were higher than those in the control group (5,7% and 8,6% respectively), but the difference did not reach statistical significance. Of further interest may be our finding that, despite anecdotal reports blaming D-penicillamine for cases of autoimmune thyroiditis, the incidence of the latter was similar among recipients and nonrecipients of the drug. Similarly, TRAB were not detected in any patient treated with D-penicillamine.

The effect of light on plasma melatonin levels in premature infants.

Recent studies have shown that full term neonates actively secrete melatonin and that light deprivation during the first 72 h of life significantly increases plasma melatonin levels. In order to evaluate pineal gland activity and responsiveness to light in premature infants, we measured plasma melatonin levels in 23 healthy infants, 33-36 weeks of gestation, during their first week of life. Nine infants (Group A) remained under constant illumination conditions for 48 hour prior to melatonin measurements. Fourteen infants (Group B) were exposed for the same time period to an artificial alternation of day and night cycles by covering the eyes of the infants with eye pads during the night (20.00-08.00 h). Mean +/- SEM plasma melatonin at 20.00 h, 04.00 h, 12.00 h and 20.00 h was 14.8 +/- 1.6, 16.2 +/- 2.8, 18.7 +/- 3.1, 20.9 +/- 3.1 pg/ml in Group A and 20.5 +/- 3.2, 22.3 +/- 2.9, 20.2 +/- 2.2, 18.5 +/- 2.2 pg/ml in Group B respectively. The differences observed between the two groups were not statistically significant. Our results indicate that at this gestational age the pineal gland is actively secreting melatonin but does not respond to the light alternations attempted. Further studies are needed in order to evaluate the developmental maturation of the pineal gland in humans.

Prolactin and growth hormone in perinatal asphyxia.

To assess the pituitary response to perinatal asphyxia, the prolactin (PRL) and growth hormone (hGH) serum concentrations were measured in 55 asphyctic (15 preterm and 40 full-term) and 35 control (15 preterm and 20 full-term) newborns at 2-4, 24, 48 and 98 h of life. At 2-4 h the median PRL in the preterm asphyctic neonates was 5.2 U/l, whereas in the preterm control newborns it was 3.2. In the full-term newborns with and without hypoxic-ischaemic encephalopathy (HIE) it was 5.8 and 3.4, respectively. In the full-term neonates with HIE the PRL remained significantly higher than in the controls up to the fourth day. At 2-4 h the median hGH in the preterm asphyctic and control newborns was 106.2 and 54.8 mU/l, respectively. In full-term newborns it was 85.0 and 40.8, respectively. The lowest hGH concentrations were found in the severe HIE. The increased PRL and hGH in asphyxia may result from a stress-related hormone release, whereas the very low hGH concentrations in severe HIE may result from a damage at the hypothalamic-hypophyseal axis.

Peripheral blood mononuclear cells from patients with rheumatoid arthritis suppress erythropoiesis in vitro via the production of tumor necrosis factor alpha.

Anemia is a frequent manifestation of rheumatoid arthritis, with a probably multifactorial etiology. We investigated the effect of peripheral blood mononuclear cell supernatants (PBMCS) from rheumatoid arthritis (RA) patients on hematopoietic colony formation in vitro, by using a methylcellulose assay. PBMCS from patients suppress in vitro erythroid (BFU-E), mixed-lineage (CFU-GEMM) and to a lesser degree granulocyte-macrophage (CFU-GM) progenitors. PBMCS from anemic RA patients were more suppressive for BFU-E than those from non-anemic patients. Addition of antibodies to tumor-necrosis factor alpha (TNF alpha) almost completely reversed the inhibition of BFU-E and CFU-GEMM, but had little effect on the CFU-GM colony formation. Antibodies to interferon-gamma (IFN gamma) and interleukin-1 (IL-1) were not effective. The above data suggest that PBMCS from RA patients suppress in vitro erythropoiesis via the production of TNF alpha; a pathogenetic role for TNF alpha in the anemia of RA can be implied.

Increased levels and positive correlation between erythropoietin and hemoglobin concentrations in newborn children of mothers who are smokers.

The mean erythropoietin concentration in the cord blood of neonates whose mothers were smokers was greater than in neonates whose mothers were not smokers. There was a significant positive correlation between erythropoietin and hemoglobin concentrations. The findings suggest that approximately one of five fetuses who are exposed to tobacco smoke are in a state of chronic hypoxia.

Prolactin, growth hormone and insulin-like growth factor-I in newborn children of smoking mothers.

OBJECTIVE: Since maternal smoking causes fetal circulatory abnormalities, as well as disturbances of the maternal endocrine equilibrium, we measured the PRL, hGH and insulin-like growth factor-I (IGF-I) concentrations in the cord and venous blood of neonates of smoking mothers to determine whether or not the tobacco smoke affects the endocrine status of the neonate. DESIGN: The above hormones were measured in the cord blood of the newborns of both smoking and non-smoking mothers. Also, PRL and hGH were determined at 24 and 72 hours after birth in newborns of both groups. PATIENTS: Fifty-three newborns of smoking and 47 newborns of non-smoking mothers were investigated. Seventeen of the newborns of the smoking and 21 of the non-smoking mothers were preterm. The remainder were full-term. MEASUREMENTS: PRL was measured with a solid-phase immunoradiometric assay, hGH with a solid-phase two-site immunoradiometric assay and IGF-I with a solid-phase radioimmunoassay after extraction with acid-ethanol. RESULTS: The median value of PRL in the 17 preterm newborns of smoking mothers was 4941 mU/I (range 1322-7230), whereas in the 21 preterm newborns of non-smoking mothers it was 2013 mU/I (range 243-4740) (P = 0.0002). The median hGH value in the above subjects was 102.0 mU/I (range 35.2-208.4) and 59.8 mU/I (range 11.6-134.2), respectively (P = 0.0039). The median IGF-I was 580.7 U/I (range 253.2-4851.1) and 530.6 U/I (range 239.6-3591.5), respectively (P = 0.429). In the 36 full-term newborns of smoking mothers the median PRL value was 5171 mU/I (range 2074-7530), whereas in the 26 full-term newborns of non-smoking mothers it was 5081 (range 244-6540) (P = 0.048). The median hGH was 69.6 mU/I (range 42.3-280.0) and 32.2 mU/I (range 6.2-200.0), respectively (P = 0.0031). Also, the median IGF-I value was 926.3 U/I (range 348.5-5344.7) and 462.1 U/I (range 250.2-1578.7), respectively (P = 0.0024). On the 3rd day the PRL in the preterm neonates of both smoking and non-smoking mothers showed the same 16.5% drop, and thus the difference between the groups was maintained. A similar reduction in the hormone levels was observed in the full term neonates. CONCLUSIONS: The findings indicate that the maternal tobacco-smoking causes disturbances of the endocrine status of the fetus, as shown by the increased levels of PRL, hGH and IGF-I, which are more pronounced between 30 and 37 weeks of gestation than at term.

Medium- and long-chain triglycerides have different effects on the synthesis of tumor necrosis factor by human mononuclear cells in patients under total parenteral nutrition.

OBJECTIVE: Lipid emulsions containing both long- and medium-chain triglycerides (LCT/MCT) have been used in total parenteral nutrition (TPN) regimens and seem to have certain advantages for seriously ill patients. The aim of the present study was to investigate the effect of lipid emulsions containing 100% LCT or 50% LCT/50% MCT on tumor necrosis factor (TNF) production by human mononuclear cells. STUDY DESIGN: This was a prospective study, in which 20 malnourished patients were randomly allocated to receive either 100% LCT or 50% LCT/50% MCT for > 30 days. We measured TNF synthesis before initiation of TPN, as well as at 15 and 30 days during TPN. SETTING: Departments of Medicine and Surgery, Patras University Medical School, Patras, Greece. PARTICIPANTS: Members of the staff of the Departments of Medicine and Surgery, Patras University Medical School. RESULTS: We found that TNF production was significantly (p < 0.01) elevated at 30 days in the LCT group, while no significant differences were detected in the LCT/MCT group. CONCLUSIONS: It is concluded that long-term TPN formulas, where LCT have been partially replaced by MCT, do not change TNF synthesis by peripheral blood mononuclear cells, and this may be beneficial in seriously ill, cachectic patients.

Growth hormone, insulin-like growth factor-I and prolactin in small for gestational age neonates.

Growth hormone (hGH), insulin-like growth factor-I (IGF-I) and prolactin (PRL) were measured in the cord and venous blood of small for gestational age (SGA) neonates in order to evaluate their endocrine status during the first 3 days of life. Although there were SGA newborns with both high and normal levels of hGH, the mean (+/- SD) concentration of hGH in the cord blood of the SGA neonates was 72.1 +/- 50.6 ng/ml, whereas in the appropriate for gestational age (AGA) newborns it was 37.0 +/- 23.5 (p = 0.001). The IGF-I in the cord blood of the SGA and the AGA newborns was 194.2 +/- 174.8 ng/ml and 77.3 +/- 50.2, respectively (p = 0.013). The PRL in the SGA and AGA newborns was 184.8 +/- 62.4 ng/ml and 126.8 +/- 60.5, respectively (p = 0.0005). On the 3rd day the hGH in the SGA babies was 50.7 +/- 41.2, whereas in the AGA it was 24.3 +/- 12.3 (p = 0.034). On the same day the IGF-I was 133.9 +/- 120.9 and 44.8 +/- 31.6, respectively (p > 0.05). Similarly, the PRL was 157.1 +/- 52.3 and 90.9 +/- 52.5, respectively (p = 0.0008). All neonates with high hGH concentrations had low IGF-I levels, whereas of those with normal hGH half had high and half normal IGF-I levels. There was no difference in the hormone levels between symmetric and asymmetric intrauterine growth-retarded infants. The findings suggest that the SGA neonates are heterogeneous comprising three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Low serum testosterone: a special feature of hepatocellular carcinoma.

OBJECTIVES: The possible role of sex hormone imbalance in hepatocellular carcinogenesis was investigated. PATIENTS AND METHODS: Ten men with hepatocellular carcinoma (HCC) and cirrhosis, 10 men with HCC without cirrhosis, 12 men with cirrhosis of various aetiologies, 8 men with secondary liver tumours and 10 normal men were studied. Plasma levels of testosterone, androstenedione, oestradiol, sex hormone binding globulin follicle stimulating hormone and luteinizing hormone were determined for all patients. RESULTS: Patients of all groups had comparable levels of oestradiol, androstenedione, sex hormone binding globulin, luteinizing hormone and follicle stimulating hormone. Low testosterone values in the serum were found for all patients with primary liver disease. Low testosterone was found even in patients with primary HCC who did not have cirrhosis or liver failure serious enough as to be responsible for the reduction of testosterone levels. On the other hand patients suffering from secondary liver tumours had normal values of serum testosterone. CONCLUSIONS: These results present an indication that low serum testosterone is a special feature of hepatocellular carcinoma.

Tumor necrosis factor production by human mononuclear cells during total parenteral nutrition containing long-chain triglycerides.

The effect of fat contained in total parenteral nutrition (TPN) regimens on the immune system is controversial. The purpose of our study was to examine whether the synthesis of tumor necrosis factor (TNF), a macrophage-derived protein with several immunomodulating effects, is influenced by the duration of TPN. We studied 20 patients on glucose- and fat-based TPN with lipid emulsions containing long-chain triglycerides (LCTs). Ten of our patients received TPN for 15 days (group A) and the other 10 for 30-40 days (group B). We measured TNF production by phytohemagglutinin- and endotoxin-stimulated peripheral blood mononuclear cells before and after TPN via enzyme-linked immunosorbent assay. The production of TNF before and after TPN was similar in group A but significantly (p less than 0.01) elevated in group B after long-term TPN. Therefore, long-term TPN containing LCTs may increase TNF production, and this may be the result of an immunomodulating effect of fat.

Development of thyrotropin circadian rhythm in infancy.

Normal children and adults show a similar pattern of diurnal variation of TSH secretion with lower values at 1100 h and higher around 2300 h. The purpose of this study was to investigate the age of appearance of TSH circadian rhythm. In 57 fullterm infants 0-6 months old and in 37 premature infants 1-4 weeks old TSH was measured at 1030, 1100, 1130 h and 2230, 2300, and 2330 h. No diurnal rhythm was detected in both premature and fullterm infants less than 4 weeks of life. After the first month of life a significant difference between AM and PM values was observed in fullterm infants. In infants 1-2 months old mean +/- SEM AM and PM values were 2.8 +/- 0.2 and 3.5 +/- 0.4 mU/L, respectively (P less than 0.025), in infants 3-4 months old 3.0 +/- 0.6 and 4.1 +/- 0.8 (P less than 0.01) and in infants 5-6 months old 1.8 +/- 0.2 and 2.6 +/- 0.3 (P less than 0.0005). These data clearly indicate that the development of TSH circadian rhythm starts after the first month of life.