bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Antibodies against Hepatitis C Virus in the Elderly: A Seroepidemiological Study in a Nursing Home and in an Open Population
Authors: Baldo V. , Floreani A. , Menegon T. , Angiolelli G. , Trivello R.
Published: April 2003

Background: The prevalence of antibodies against hepatitis C virus (anti-HCV) increases in the general population with advancing age. Several discrepancies exist in the epidemiology of HCV, however, when selected elderly population groups are tested. Objective: To evaluate the HCV prevalence in two groups of elderly people living in the same geopgraphical area of northeast Italy, i.e., one including residents of a nursing home, the other including subjects living at home. Methods: The overall sample included 496 subjects (mean age 79.31 ± 8.9 years); 288 were in a nursing home, and 208 were living at home. Enrollment in the latter group was based on all subjects over 65 years old listed under the public health service in the same district. The overall rate of adhesion to the study was 90%. Each subject was administered an anonymous questionnaire testing sociodemographic data and risk factors for HCV infection. Serological tests included: anti-HCV and hepatitis B virus serum markers. Multiple logistic regression analysis was performed to evaluate risk factors for anti-HCV positivity. Results: Anti-HCV positivity was found in 34 of 288 (11.8%) elderly in the nursing home and in 23 of 208 (11.1%) in the open population. When the total population was considered, females exhibited a significantly a higher prevalence of anti-HCV than males (13.4 vs. 7.5%, p < 0.05). In both males and females, the highers rate of anti-HCV prevalence was found among the 75- to 79-year-old subjects. A decline in anti-HCV prevalence was observed in the very old subjects (over 80 years of age). None of the anti-HCV-positive subjects was found to be coinfected with hepatitis B surface antigen. However, multiple logistic regression analysis identified the age group between 70 and 79 years, female gender, and positivity for antihepatitis B surface antigen and/or antihepatitis B core antigen as independent variables significantly associated with HCV prevalence. Conclusions: The prevalence of anti-HCV proved identical among elderly people living in the nursing home or at home, suggesting that nursing homes do not represent a risk factor for HCV infections; the significant association between HCV prevalence and antihepatitis B surface antigen and/or antihepatitis B core antigen positivity supports a common route of transmission of the two viruses; these findings would suggest that there was an epidemic of HCV infection during the Second World War and in the years immediately afterwards.
Life Shortening and Physician Assistance in Dying: Euthanasia from the Viewpoint of German Legal Medicine
Authors: Oehmichen M. , Meissner C.
Published: April 2003

Background: Around the world heated debates have broken out on the topic of active euthanasia. Specialists in the field of ‘forensic medicine’ have taken full part in these discussions. Objective: The present survey from the point of view of forensic medicine begins with a look at current terminology and at the laws pertaining to euthanasia in Germany. These laws are then contrasted with actual practice, including a description of the increasing acceptance of active euthanasia by the German population and its legalization in Holland. The main argument against active euthanasia is that its formal acceptance in law would cause the dam of restraint to burst, culminating in widespread misuse, as already seen in recent serial killings by nurses in hospitals and homes for the elderly around the world. Conclusions: Contrasted to this are the arguments for taking active steps at the end of life, including emotional considerations such as the revulsion against mechanized medicine and the fear of pain and rational arguments such as the necessity to end a ‘life unworthy of life’, to save medical costs, and obtaining prior consent in ‘living wills’. Such considerations have put in jeopardy the moral integrity of the medical profession – and thus the layperson’s trust in physicians – around the world. In Germany especially the history of mass killing during the Nazi era constitutes a fundamental argument against active euthanasia. As a consequence, in Germany active euthanasia will not receive legal sanction, although recommendations on rendering dying more bearable are permitted.
Pain and Alzheimer’s Disease
Authors: Pickering G. , Eschalier A. , Dubray C.
Published: April 2003

Literature on pain management in Alzheimer’s disease is slowly emerging and this review deals with different aspects of pain in this growing population. Clinical pain, experimental pain and assessment of pain in cognitively impaired patients are presented. Treatment of pain is also discussed. This review calls for more studies and clinical trials with a view to improve the comfort and quality of life of patients suffering from Alzheimer’s disease.
Immunophenotypical Changes of T Lymphocytes in the Elderly
Authors: Ginaldi Lia , De Martinis Massimo , Modesti Marco , Loreto Francesca , Corsi Maria Pia , Quaglino Dennis
Published: April 2003

Background: Substantial changes in both representation and function of T lymphocyte subsets have been reported with advancing age. However, till now, no systematic studies focused on age-dependent changes in the expression intensity of the major T lymphocyte surface receptors. Objective: The present study was undertaken in order to establish age-related differences in lymphocyte subpopulations by simultaneously measuring three surface antigens in young and elderly people. Method: Peripheral blood T cell subsets from 20 healthy elderly individuals and 15 healthy young adult donors were examined by means of a quantitative three-color flow cytometry method. Results: Activated (HLA-DR+) and memory (CD45RO+) T cells, CD3+CD7– T lymphocytes, and cells expressing natural killer (NK) markers (CD3–CD56+ NK cells and CD3+CD56+ T lymphocytes) were expanded, whereas T lymphocytes expressing the adhesion molecule CD62L were lower in elderly compared with young donors. In addition to alterations in the percentages of T cell subsets during senescence, several changes in the intensity expression of T cell antigens were also detected. CD3 antigen expression was downregulated on total T lymphocytes as well as on the memory T cell subset, while CD56+ T cells exhibited increased CD3 levels. Moreover, CD2 expression, unchanged on NK cells, was upregulated on T lymphocytes from elderly subjects. CD3+CD7– T cells exhibited increased expression of CD8 antigen, while the intensity expression of HLA-DR on activated T cells and CD7 on both T and NK lymphocytes was decreased. T cells from elderly subjects also exhibited higher expression of CD50 and CD62L adhesion molecules as compared with young ones. Conclusion: These T cell antigen expression modulations during senescence, in addition to the alteration in the frequency of the various T lymphocyte subsets, could contribute to the complex remodeling of the immune function characteristic of the elderly.
Initial Lesions of Vascular Aging Disease (Arteriosclerosis)
Authors: Kunz J.
Published: April 2003

Background: In contrast to the well-known morphologic lesions of arteriosclerosis, the initial changes of the disease are less obvious. Commonly, functional disturbances of the endothelium, endothelial dysfunction, are suggested. On the other hand the significance of age-dependent changes in the extracellular matrix with their important role in vessel wall permeability and other features associated with arteriosclerosis should not be overlooked. New topics deal with possible infectious factors, the genetic basis of the disease and the particularities of the unstable atheroma. Objective: Alterations in nitric monoxide and endothelin-1 balance of the endothelium are the key events in the initiation of arteriosclerosis induced by oxidized lipoproteins, cigarette smoking and endotoxin. This frequently supposed mechanism contrasts with earlier opinions on the primary alterations in glycosaminoglycan metabolism and other components of the extracellular matrix against atherogenic factors like hypertension, stress and physical inactivity. Based on a survey of the literature and our own experimental experiences, these changes in connection with the morphometrically determined age-conditioned increase in vascular wall thickness and the above-mentioned new topics on arteriosclerosis were analyzed. Conclusion: The initial lesions of arteriosclerosis starting in youth seem to be fundamentally different from those beginning in old age. The first step in the development of fatty streaks in the arteries of young people is endothelial dysfunction with a decreased formation of nitric monoxide and an increased expression of adhesion molecules. In comparison the genesis of arteriosclerosis in advanced age is characterized by metabolic changes in the endothelium combined with age-conditioned alterations in the extracellular matrix resulting in faster progression of the disease in old age. The multicausal genesis of arteriosclerosis cannot be doubted even if cooperation with infectious factors cannot be excluded. The histopathologic peculiarities of unstable atheroma are described.
Roma-Geburtsrad: 1 Jahr klinische Erfahrung an einem Schwerpunktkrankenhaus
Authors: Rohrbacher A. , Salzer H.
Published: April 2003

Fragestellung: Prüfung von Sicherheit und Praktikabilität der Entbindung aus Schädellage am Roma-Geburtsrad. Methode: Ein Jahr klinische Erfahrung (1.12.1995–30.11.1996) mit dem Roma-Geburtsrad an der Gynäkologisch-Geburtshilflichen Abteilung des Wilhelminenspitals in Wien verglichen mit den Ergebnissen des Normalkollektives vor Anschaffung desselben. Ergebnisse: Von 1555 Geburten wurden 1377 (89%) spontan durchgeführt, wobei 209 (15%) Frauen am Roma-Geburtsrad entbunden haben. Im Vergleich mit dem Normalkollektiv 1 Jahr vor Einsatz des Roma-Geburtsrades war die Gesamtgeburtsdauer um etwa 30% kürzer, die Geburtswege bei 44% der Frauen intakt und der Analgetikaverbrauch um 8–27% reduziert. Schlussfolgerung: Die Schädellagegeburt am Roma-Rad zeigt Vorteile bezüglich Geburtsdauer und Akzeptanz der Gebärenden bei gleichbleibender Sicherheit für Mutter und Kind.
LSD- und Cannabis-Konsum während der frühen Schwangerschaft mit gutem perinatalen Ausgang
Authors: von Mandach Ursula , Rabner Michael M. , Wisser Joseph , Huch Albert
Published: April 2003

Im dargestellten Fall geht es um eine 27jährige Patientin, die bis zum Zeiptunkt des positiven Schwangerschaftstests, entsprechend 74/7 Schwangerschaftswochen (p.c.), täglich einen Joint (Cannabis) und 20 Zigaretten (Tabak) geraucht hat. Am 20. Tag p.c. erfolgte ein LSD-Minitrip. Das Sichten der Literatur ergab beim Tier in vitro Chromosomenaberrationen mit LSD. Beim Menschen stehen Fehlbildungen an den Extremitäten und Augendysplasien an vorderster Stelle. Cannabis verursacht beim Tier und beim Menschen eine Veränderung der dopaminergen Aktivität. Unsere Empfehlung lautete daraufhin, das Kind in utero auszutragen, aber gut zu überwachen. Die Patientin gebar schliesslich spontan am Termin einen lebensfrischen Knaben mit einem Geburtsgewicht zwischen der 5. und 50. Perzentile und einer Länge zwischen der 50. und 90. Perzentile, normalen pH-Werten von Nabelschnurarterie und -vene und Apgar-Werten von 7/9/10. Das Kind wies keine äusserlichen Fehlbildungen auf und verhielt sich unauffällig. Im Zusammenhang mit einem vermuteten LSD-Konsum soll die Aufmerksamkeit auf Skelett- und Augendysplasien gerichtet werden. Sowohl für LSD als auch insbesondere für Cannabis gilt es, die intellektuelle Entwicklung der Kinder im Auge zu behalten.
Sexualität in der zweiten Lebenshälfte
Authors: Schmid Mast Marianne , Hornung Rainer , Gutzwiller Felix , Buddeberg Claus
Published: April 2003

Der Stand des Wissens über das sexuelle Erleben und Verhalten im mittleren und höheren Lebensalter ist im Vergleich zu anderen sexologischen Forschungsgebieten bisher eher bescheiden. Dies ist zum einen durch die immer noch starke Tabuisierung von Fragen der Sexualität im Alter zu erklären und zum anderen durch ein beschränktes Verständnis von Faktoren, welche die Sexualität beeinflussen. In der vorliegenden Übersichtsarbeit werden Befunde zur Sexualität in der zweiten Lebenshälfte aus der Perspektive von verschiedenen Disziplinen dargestellt. Dabei stehen Geschlechtsunterschiede in bezug auf das Sexualleben und der Einfluss von kritischen Lebensereignissen auf die Sexualität von Frauen in der zweiten Lebenshälfte im Vordergrund. Neben restriktiven gesellschaftlichen Normen und individuellen Persönlichkeitsfaktoren haben auch physiologische Veränderungen in der Menopause einen Einfluss auf die Sexualität. Die besondere Situation von partnerlosen älteren Frauen sowie die in diesem Altersabschnitt auftretenden Veränderung der partnerschaftlichen Sexualität werden diskutiert. Aus der multidisziplinären Betrachtungsweise werden abschliessend einige Empfehlungen für die frauenärztliche Praxis abgeleitet.
Symptomatic Endpoints for Venous Thromboembolism Treatment
Authors: Anderson D.R.
Published: April 2003

Clinical trials evaluating antithrombotic therapy for the treatment of deep vein thrombosis require that the diagnosis is confirmed by objective testing prior to patient entry into the study. Two basic approaches may then be taken for defining endpoints to assess the efficacy of antithrombotic treatment. In the first approach, the diagnostic test is repeated at a predetermined time following the initiation of the interventional therapy. In the second approach, no further diagnostic testing is routinely performed for a minimum of 3 months following patient enrolment after the diagnosis of venous thromboembolism for evidence of symptomatic recurrent deep vein thrombosis or pulmonary embolism. This approach is used in later-phase clinical trials to examine whether a novel therapeutic agent is as safe and effective as the drugs currently used for management of venous thromboembolism. Symptomatic recurrent deep vein thrombosis and pulmonary embolism confirmed by objective testing are clinically important causes of patient morbidity, place patients at increased risk of fatal pulmonary embolism, cause increased rates of chronic thromboembolic complications and have resource consequences. Studies utilizing symptomatic recurrent deep vein thrombosis or pulmonary embolism as endpoints have been responsible for most of the treatment advances in the management of patients with venous thromboembolism that have been observed in the past 40 years. Although confirmation of recurrent venous thromboembolism is not possible in all patients, clinical trials using rigorous methodology can minimize the potential bias caused by the limitations of diagnostic test results. There is a need to develop better objective tests in the future, to distinguish previous from recurrent venous thromboembolism.
The Procoagulant Effect of Thrombin on Fibrin(ogen)-Bound Platelets
Authors: Sanders Marijke W. , Nieuwenhuys Cécile M.A. , Feijge Marion A.H. , Rook Martin , Béguin Suzette , Heemskerk Johan W.M.
Published: April 2003

In a final stage of activation, platelets become procoagulant because of the appearance of phosphatidylserine (PS) at the membrane outer surface. This PS exposure requires a rise in cytosolic [Ca2+]i, is accompanied by formation of membrane blebs, and stimulates the formation of thrombin from its precursor prothrombin. Here, we investigated whether thrombin, as a potent platelet agonist, can induce this procoagulant response in plasma-free platelets interacting with fibrin or fibrinogen through their integrin αIIbβ3 receptors. First, in platelets that were stimulated to spread over fibrin or fibrinogen surfaces with adrenaline, addition of thrombin and CaCl2 caused a potent Ca2+ signal that in about 30% of the cells was accompanied by exposure of PS. At low doses, integrin αIIbβ3 receptor antagonist (RGD peptide) inhibited platelet spreading as well as thrombin-evoked PS exposure. Second, in platelet-fibrinogen microaggregates that were preformed in the presence of adrenaline, thrombin/CaCl2 induced PS exposure and bleb formation of about 35% of the cells. Third, a potent, thrombin-dependent stimulation of prothrombinase activity was measured in platelet suspensions that were incubated with a fibrin clot. These results indicate that, in the absence of coagulating plasma, thrombin is a moderate inducer of the procoagulant response of platelets, once integrin αIIbβ3-mediated interactions are stimulated (by adrenaline) and CaCl2 is present.
Endothelial Function, Variables of Fibrinolysis and Coagulation in Smokers and Healthy Controls
Authors: Enderle M.D. , Pfohl M. , Kellermann N. , Haering H.U. , Hoffmeister H.M.
Published: April 2003

Objective: To asses endothelial function and variables of fibrinolysis and coagulation in smokers compared to healthy controls. Methods: Flow-associated dilation as a marker for peripheral endothelial function and intima media thickness as a marker for early morphologic vascular changes were measured in otherwise healthy smokers (n = 30, 16 males and 14 females, age: 40.6 ± 11.3 years, body mass index 24.9 ± 3.7 kg/m2) and non-smoking controls matched for age and sex using high-resolution ultrasound. Variables of the coagulation system (thrombin-antithrombin III complex, fibrinogen) and fibrinolysis (tissue-plasminogen activator, plasmin-α2-antiplasmin complex) were determined by ELISA and plasminogen activator inhibitor activity by means of a chromogenic substrate test. Results: Compared to the non-smoking controls, flow-associated vasodilatation was significantly reduced (6.9 ± 4.4 vs. 10.5 ± 6.2%, p = 0.01) and intima media thickness tended to be increased (0.58 ± 0.12 vs. 0.52 ± 0.14 mm, p = 0.08) in smokers. The thrombin-antithrombin III complex, fibrinogen, plasmin-α2-antiplasmin complex, tissue-plasminogen activator and plasminogen activator inhibitor activity did not differ between smokers and controls. Conclusion: Our data indicate that peripheral endothelial dysfunction is common in smokers even without major alterations in molecular markers of the coagulation and fibrinolysis system.
Children’s Theory of Mind: An Experiential Interpretation
Authors: Nelson, Katherine , Plesa, Daniela , Henseler Sarah
Published: April 2003

The interpretive and theory versions of children’s theory of mind as discussed by Astington and Olson are reconsidered in the light of an experiential theory of cognitive development. Data from adults’ responses to a theory of mind task are reported, indicating that many adults (college students) provide interpretive explanations while others give straightforward logical-causal theoretical explanations of actions. Evidence from naturalistic studies of young children as well as their explanations offered in experimental situations suggest that they rely on background experientially based knowledge to interpret theory of mind tasks. We argue that a logical-causal theory of human action based on mental states is a developmental product of interpretive narrative and not its basis.
Levinas and the Ethical Context of Human Development
Authors: Vandenberg Brian
Published: April 2003

Research on infancy and the philosophy of Levinas are integrated, suggesting that human development is forged within an ethical, relational context, with particular individuals, embodied in ordinary, daily, concrete acts of giving, care and exchange. Ethics is immanent in human conduct and moral principles are derived from the acts of relatedness and care essential to human life, present from the earliest, first moments of life. Ethics as first philosophy suggests that the primordial relational context of development necessarily entails ethical responsibility, revealed most visibly in love and death.
Combination Reperfusion Therapy with Eptifibatide and Tenecteplase for Acute Myocardial Infarction
Authors: Roe Matthew T. , Giugliano Robert P. , Harrington Robert A. , Gibson C. Michael , Strony John , Kitt Michael M. , Califf Robert M. , Braunwald Eugene
Published: April 2003

Combination reperfusion therapy with partial-dose fibrinolytics and glycoprotein (GP) IIb/IIIa inhibitors for patients with acute myocardial infarction has been shown to accelerate and improve reperfusion compared with fibrinolytic monotherapy. Tenecteplase is a single-bolus fibrinolytic agent that has been shown to have equivalent efficacy to alteplase (the current ‘gold-standard’ fibrinolytic agent), and thus has the potential to simplify fibrinolytic dosing. Eptifibatide is a synthetic GP IIb/IIIa inhibitor that has been evaluated as an adjunct to fibrinolytic therapy. The combination of various doses of tenecteplase with eptifibatide will be evaluated in the dose-finding phase of the Integrilin and Tenecteplase for Acute Myocardial Infarction (INTEGRITI) trial to determine the optimal dose to use in the dose confirmation phase. Tenecteplase monotherapy will be compared with optimal-dose tenecteplase plus eptifibatide in the dose confirmation phase of the trial. The primary end point of both phases of the trial will be Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in the infarct-related artery at 60 min. INTEGRITI will also evaluate other useful indicators of reperfusion efficacy, including the corrected TIMI frame count, the TIMI myocardial perfusion grade, ST segment resolution assessed with serial static electrocardiograms and continuous ST segment monitoring, and plasma/serum markers. Thus, the INTEGRITI trial will extensively evaluate the relative benefits of combination reperfusion therapy for the treatment of acute myocardial infarction, and will aid in the planning of a subsequent large-scale phase III trial.
Testing for Linkage underRobust Genetic Models
Authors: Guerra R. , Wan Y. , Jia A. , Amos C.I. , Cohen J.C.
Published: April 2003

Robust genetic models are used to assess linkage between a quantitative trait and genetic variation at a specific locus using allele-sharing data. Little is known about the relative performance of different possible significance tests under these models. Under the robust variance components model approach there are several alternatives: standard Wald and likelihood ratio tests, a quasilikelihood Wald test, and a Monte Carlo test. This paper reports on the relative performance (significance level and power) of the robust sibling pair test and the different alternatives under the robust variance components model. Simulations show that (1) for a fixed sample size of nuclear families, the variance components model approach is more powerful than the robust sibling pair approach; (2) when the number of nuclear families is at least ∼100 and heritability at the trait locus is moderate to high (>0.20) all tests based on the variance components model are equally effective; (3) when the number of nuclear families is less than ∼100 or heritability at the trait locus is low (<0.20), on balance, the Monte Carlo test provides the best power and is the most valid. The different testing procedures are applied to determine which are able to detect the known association between low density lipoprotein cholesterol and the common genotypes at the locus encoding apolipoprotein E. Results from this application show that the robust sibling pair method may be more effective in practice than that indicated by simulations.
Multipoint Linkage Analysis
Authors: Halpern Jerry , Whittemore Alice S.
Published: April 2003

Multipoint linkage analysis is commonly used to evaluate linkage of a disease to multiple markers in a small region. Multipoint analysis is particularly powerful when the IBD relations of family members at the trait locus are ambiguous. The increased power arises because, unlike single-marker analyses, multipoint analysis uses haplotype information from several markers to infer the IBD relations. We wish to temper this advantage with a cautionary note: multipoint analysis is sensitive to power loss due to misspecification of intermarker distances. Such misspecification is especially problematic when dealing with closely spaced markers. We present computer simulations comparing the power of single-point and multipoint analyses, both when IBD relations are ambiguous, and when the intermarker distances are misspecified. We conclude that when evaluating markers in a small region to confirm or refute previous findings, a situation in which p values of modest statistical significance are important, single marker analyses may provide more reliable measures of the strength of support for linkage than multipoint statistics.
A Unified Approach to Adjusting Association Tests for Population Admixture with Arbitrary Pedigree Structure and Arbitrary Missing Marker Information
Authors: Rabinowitz Daniel , Laird Nan
Published: April 2003

A general approach to family-based examinations of association between marker alleles and traits is proposed. The approach is based on computing p values by comparing test statistics for association to their conditional distributions given the minimal sufficient statistic under the null hypothesis for the genetic model, sampling plan and population admixture. The approach can be applied with any test statistic, so any kind of phenotype and multi-allelic markers may be examined, and covariates may be included in analyses. By virtue of the conditioning, the approach results in correct type I error probabilities regardless of population admixture, the true genetic model and the sampling strategy. An algorithm for computing the conditional distributions is described, and the results of the algorithm for configurations of nuclear families are presented. The algorithm is applicable with all pedigree structures and all patterns of missing marker allele information.
Water and Sodium Retention during Short-Term Administration of Growth Hormone to Short Normal Children
Authors: Lampit Meir , Nave Tova , Hochberg Ze’ev
Published: April 2003

GH treatment of adult patients with GH deficiency (GHD) or healthy volunteers results in weight gain and fluid and sodium retention. In the present study we have challenged normal short children with dehydration and water load, and evaluated their water and sodium clearance, plasma renin activity (PRA) and aldosterone over 4 weeks of GH administration. Eleven prepubertal short normal children, aged 4–9 years, were the subjects of this study. Recombinant GH was administered daily at a dose of 2.5 units/m2. Dehydration and water load experiments were conducted before GH (day 0) and on days 3, 7 or 28 of GH. An initial 15-hour fast ended with a 3-hour urine collection. A tap-water load of 800 ml/m2 was given orally. Urinary volumes were followed hourly for 3 h, as were urinary and serum creatinine, Na, K, aldosterone, plasma osmolality and PRA. Before GH therapy the subjects excreted within 2 h a mean 42% and within 3 h a mean 65% of the load. After 3 days of GH therapy the same children retained water significantly and excreted only 22 (p < 0.02) and 45% (p < 0.05) of the load volume, respectively. Calculating the free water clearance revealed no effect of GH therapy, whereas the fractional excretion of sodium and potassium decreased significantly by day 3 of GH administration, along with an increase in PRA and serum aldosterone. All these changes normalized by days 7 and 28 of GH therapy. It is concluded that short-term administration of GH to short normal children results in a transitory mild retention of sodium and a secondary water retention, and suggests that the primary event leading to sodium retention during the early phase of GH therapy of short normal children is an inappropriate increase in PRA.
Plasma Levels of Insulin-Like Growth Factor (IGF)-I, IGF-II and IGF-Binding Protein-3 in the Evaluation of Childhood Growth Hormone Deficiency
Authors: Rikken Berthon , van Doorn Jaap , Ringeling André , van den Brande Jan Leo , Massa Guy , Wit Jan Maarten
Published: April 2003

Background: Traditionally, measurement of plasma IGF-I and more recently of IGFBP-3 are used to distinguish GHD from idiopathic short stature in slowly growing children, using a single blood sample. In earlier studies it was claimed that IGFBP-3 was superior to IGF-I, but more recently doubts around this claim have arisen. The role of serum IGF-II has never been studied extensively. On theoretical grounds, it can also be hypothesized that molar ratios of these peptides might be of additional value. Design: Retrospective, multicentre, cohort study. Patients: 96 children evaluated for short stature. Methods: Serum IGF-I, IGF-II, IGFBP-3 and various molar ratios were, after correction for age and sex using SD scores, compared to the maximum serum GH peak after two standard provocation tests using four different methods (t-test, χ2, likelihood ratios and ROC curves). In addition, the correlations between these parameters and the short-term (1 year) and long-term (3 years) response to GH therapy were calculated. Results: IGF-I performed better than IGFBP-3, but the best results were achieved by the molar ratio IGF-I:IGF-II. However, IGFBP-3 correlated better with the short-term response to GH therapy than IGF-I or the ratios, and none of the parameters investigated was found to be related to the response of long-term GH therapy.
Does Vitamin D Receptor Polymorphism Influence the Response of Bone to Brisk Walking in Postmenopausal Women?
Authors: Tsuritani Ikiko , Brooke-Wavell Katherine S.F. , Mastana Sarabjit S. , Jones Peter R.M. , Hardman Adrianne E. , Yamada Yuichi
Published: April 2003

Vitamin D receptor (VDR) polymorphism may be a genetic factor affecting bone mineral density (BMD). This study examined the interaction of VDR genotype with the effect of an exercise intervention on bone measurements in UK postmenopausal women. 33 walkers, who completed 20.4 ± 3.9 (mean ± SD) min day–1 of brisk walking over 1 year, and 36 controls agreed to give DNA samples. BMD was measured at the lumbar spine, femoral neck and calcaneus by dual energy X-ray absorptiometry and broadband ultrasonic attenuation (BUA) was measured at the calcaneus. VDR genotype was determined by BsmI restriction fragment length polymorphisms and the presence, or absence, of the restriction site was signified by ‘b’ or ‘B’, respectively. At baseline there was no significant difference in BMD between VDR genotypes, but BUA was significantly higher in the BB genotype than in the Bb or bb genotype. Although there was no significant difference in 1-year change (%) in BMD and BUA between the three genotypes, the 1-year changes in spinal BMD and BUA in the bb walkers (0.75 and 2.35%, respectively) were significantly different from those in the bb controls (–1.25 and –6.10%, respectively). These results suggest that in the bb genotype of VDR, bone may be more responsive to exercise than in other VDR genotypes in British postmenopausal women.
Heart Failure Induced by Pheochromocytoma: Laparoscopic Treatment and Intraoperative Changes of Several New Cardiovascular Hormones
Authors: Col V. , de Cannière L. , Messaoudi L. , Michel L. , Donckier J.
Published: April 2003

Since 1992, adrenalectomy for pheochromocytoma has been recognized as a safe and efficient technique when performed by a laparoscopic approach. Most of the cases of pheochromocytomas treated as such and published in the literature were not associated with malignant hypertension and acute heart failure. We report the case of a 23-year-old woman who presented with this clinical picture and show that laparoscopic adrenalectomy may be as safe and efficient as conventional adrenalectomy when performed in this situation. The intraoperative changes in the secretion of catecholamines, endothelin-1, angiotensin II, N- and C-terminus of atrial natriuretic factor prohormone were also analyzed. Noradrenaline release during tumor dissection was associated with a stimulation of atrial natriuretic factor.
Effects of Dexamethasone and Dexamethasone plus Naltrexone on Pituitary Response to GnRH and TRH in Normal Women
Authors: la Marca Antonio , Torricelli Michela , Morgante Giuseppe , Lanzetta Danila , De Leo Vincenzo
Published: April 2003

The hypothesis that glucocorticoids have a direct central inhibitory effect on the reproductive axis is sutained by the identification of glucocorticoid receptors on GnRH-secreting neurons and gonadotropic pituitary cells. It has been proposed that glucocorticoids and opioids interact centrally in the regulation of the GnRH-LH axis. The inhibitory effect of glucocorticoids may manifest not only directly through the hormone-receptor link, but also indirectly through an increase in opioid tone. The aim of this study was to evaluate the role of glucocorticoids and glucocorticoids combined with an opioid antagonist, in the regulation of basal and GnRH- and TRH-stimulated secretion of LH, FSH and Prl in 7 women with normal menstrual cycles. Blood samples were obtained every 10 min for an hour. GnRH (50 μg) and TRH (200 μg) were administered and blood sampling was continued every 15 min for 2 h (day 1). At 5 a.m. the next day, naltrexone (50 mg) was given and at 8 a.m. the GnRH-TRH test was repeated (day 2). At 5 a.m. on day 3, the patients took 2 mg oral dexamethasone and the test was repeated. At 5 a.m. on day 4, the patients took naltrexone and dexamethasone and at 8 a.m. the GnRH-TRH test was repeated. Administration of naltrexone did not cause significant changes in basal concentrations of LH and FSH and their response to GnRH. The area under the curve of the LH response to GnRH on day 3 was significantly less than on days 1, 2 and 4. Administration of naltrexone (day 2) did not cause any significant increase in basal and TRH-stimulated levels of Prl with respect to day 1. On day 3, dexamethasone caused a reduced response of Prl to TRH. Pretreatment with naltrexone (day 4) prevented this reduction. These results suggest that suppression of the response of LH to GnRH induced by dexamethasone may be partly mediated by endogenous opioids. Dexamethasone led to a reduction in the response of Prl to TRH, and naltrexone blocked this suppression. Hence the suppression of Prl and LH by dexamethasone must be partly mediated by endogenous opioids, which must therefore inhibit pituitary secretion of Prl.
Genetic Determinants of Bone Mass
Authors: Audí Laura , García-Ramírez Marta , Carrascosa Antonio
Published: April 2003

A genetic contribution to bone mass determination was first described in the early 70s. Elucidation of gene contribution to this has since been attempted through studies analyzing associations between bone mass acquisition and/or maintenance and polymorphic variations of several genes. The first to be described was the vitamin D receptor gene (VDR), initially claimed to contribute to almost 75% of the genetic variation in bone mineral density (BMD) in twin and general population studies. Not all of the studies published to date conclude that a clear relationship exists between polymorphic VDR alleles and BMD, and the molecular basis for the VDR gene polymorphisms influence on bone mineralization has not yet been clarified. Since then, other genes with a significant role in bone metabolism such as estradiol receptor, collagen type 1α1, TGF-β1, interleukin-6, calcitonin receptor, α2-HS-glycoprotein, osteocalcin, calcium-sensing receptor, interleukin-1 receptor antagonist, β3-adrenergic receptor, apolipoprotein E, PTH, IGF-I and glucocorticoid receptor have been analyzed. Some polymorphic variations in these genes have been associated in some works with significant differences in BMD, with even more significant contributions when associations of different gene polymorphisms were analyzed. Again, the molecular basis for the contribution of these alleles to bone mass determination has not yet been described. A different approach has been attempted by linkage analysis of loci involved in bone density in pedigrees with low BMD using BMD as a quantitative trait. Recent results do not confirm, in these families, any association with any of the previously reported genes, but rather with other as yet unidentified genes. The genetic contribution to mild variations in the general population, as a result of environmental and endogenous individual influences, probably differs completely from that providing a pathologic BMD.
Long-Term Treatment of Growth Hormone Insensitivity Syndrome with IGF-I
Authors: Ranke M.B. , Savage M.O. , Chatelain P.G. , Preece M.A. , Rosenfeld R.G. , Wilton P.
Published: April 2003

A total of 33 patients (17 female, 16 male) with Laron syndrome (n = 31) or hGH-1 gene (n = 2, type IA deletion) from 22 centres in 12 countries were enrolled in a study conducted by Pharmacia & Upjohn, Stockholm, which was designed to test the efficacy, in terms of growth promotion and safety, of IGF-I (IgefTM). The patients were treated with 40–120 μg/kg IGF-I s.c. twice daily after meals. After the study ended, the patients continued to be treated on an individual basis. The results of 17 patients, who were treated for 48 months or longer were available for the present analysis. Six patients were treated for up to 72 months. When treatment started, the mean age of these patients (8 female, 9 male) was 9.1 (3.7–13.5) years and mean height was –6.5 ± 1.3 SDS. At the end of the observation period, the mean age of the 17 patients was 14.2 (9.1–17.7) years and mean height was –4.9 ± 1.9 SDS. All patients showed a significant increase in growth during the final year on IGF-I, with two of them reaching the age-corresponding 3rd centile. The total gain in height (ΔHT) was 1.7 ± 1.2 SDS. ΔHT SDS correlated negatively with age at onset of treatment (R2 = –0.78, p < 0.02). BMI was 0.6 ± 1.8 SDS at start of treatment and 1.8 ± 1.5 SDS at the end of observation. Total ΔHT SDS correlated positively with total ΔBMI SDS (R2 = 0.59, p < 0.01). Long-term treatment of patients with GHIS thus proved to be effective in promoting growth. If treatment is started at an early age, there is considerable potential for achieving height normalisation. The treatment modalities need to be optimized with respect to the growth-promoting and metabolic effects of IFG-I.
Hypoglycemic Effects of Insulin-Like Growth Factor-1 in Experimental Uremia: Can Concomitant Growth Hormone Administration Prevent This Effect?
Authors: Kovacs G.T. , Worgall S. , Schwalbach P. , Steichele T. , Mehls O. , Rosivall L.
Published: April 2003

The risk of hypoglycemia limits the clinical application of insulin-like growth factor-1 (IGF-1). Our studies aimed to evaluate the mode of occurrence as well as the prevention of this side effect. Acute administration (i.v. infusion) of IGF-1 in subtotal nephrectomized uremic (U), sham-operated ad libitum fed control (C) and sham-operated pair-fed control (P) rats led to hypoglycemia, though more expressed in P. Serum glucose levels decreased within 60 min after the IGF-1 administration by 40% in U, by 45% in C and by 52% in P (p < 0.05, U vs. P). Chronic administration (7 days) of 1, 4 and 8 mg/kg/day IGF-1 in U rats led to hypoglycemia in an increasing manner as the dose of IGF-1 increased. On the first day, 2 h after injection, serum glucose levels were 116.5 ± 8.6, 110.4 ± 12.4, 60,3 ± 19.2 and 50.6 ± 18.3 mg/dl, respectively (p < 0.01). One week later, IGF-1 therapy proved to be less hypoglycemic in all the groups. On day 7, 2 h after injection the serum glucose levels were 118.9 ± 23.8, 89.0 ± 23.9 and 66.0 ± 32.0, respectively (in comparison to day 1 for 4 and 8 mg/kg/day IGF-1 p < 0.05). The combined effect of 4 mg/kg/day IGF-1 and 10 IU/kg/day growth hormone (GH) was also studied in U and P animals. Two hours after the first injections of IGF-1 serum glucose levels decreased in U from 120.0 ± 11.3 to 49.2 ± 21.6 mg/dl, while IGF-1 plus GH decreased the glucose level from 122.0 ± 15.5 to 81.3 ± 24.7 mg/dl (p < 0.05 IGF-1 vs. IGF-1 + GH). The hypoglycemic effect of IGF-1 was less expressed by long-term treatment and simultanous administration of GH overcame the glucose-lowering effect of IGF-1 (serum glucose levels on day 11 one hour after the injections: 73.7 ± 15.3 mg/dl with IGF-1, and 111.0 ± 7.8 mg/dl with IGF-1 + GH). Methylprednisolone (MP) did not significantly alter the former effects of IGF-1 and GH. In summary, IGF-1 leads to hypoglycemia in control and uremic rats in a dose-dependent manner. This effect becomes less expressed after prolonged administration. GH attenuates the hypoglycemic effect of IGF-1. This suggests that the combined GH and IGF-1 treatment is more effective and less dangerous in correcting uremic growth failure.
Effect of Vitamin D3 Treatment in the Neonatal or Adolescent Age (Hormonal Imprinting) on the Thymic Glucocorticoid Receptor of the Adult Male Rat
Authors: Csaba György , Inczefi-Gonda Ágnes
Published: April 2003

Single neonatal treatment with 25 μg vitamin D3 significantly decreased the thymic glucocorticoid receptor density (Bmax) of 6-week-old male rats. In females, a similar treatment did not cause any changes. Single vitamin D3 treatment (50 μg) during adolescence (i.e. 6-week-old animals) significantly increased the glucocorticoid receptor density in adult (10-week-old) males. No significant changes in receptor affinity (Kd) could be observed. Considering that in earlier experiments similar neonatal treatments influenced bone mineral mass and sexual behavior, the hormonal imprinting effect of vitamin D3 and its harmful effect on the development of other members of the steroid receptor superfamily, seems to be unquestionable.
Immunological Models of Type 1 Diabetes
Authors: Luppi Patrizia , Trucco Massimo
Published: April 2003

Type 1 diabetes mellitus is a serious health problem that affects several million new people each year. Although it is recognized that type 1 diabetes results from an autoimmune destruction of the insulin-producing β-cells in the pancreatic islets of Langerhans, its etiopathogenesis is still not well understood. A certain genetic phenotype seems to be required, but it is not sufficient per se to trigger diabetes development. Numerous studies have pointed to the role of infectious agents as important environmental factors in breaking ‘self’-tolerance and triggering activation of autoreactive T cells. Activated T cells, in turn, destroy target cells harboring the corresponding tissue-specific self-antigen, causing organ damage and loss of function. Several theories have been proposed to explain how environmental factors can initiate and/or perpetuate autoimmunity towards pancreatic β-cells.
Effects of Gender, Body Composition and Birth Size on IGF-I in 7- and 8-Year-Old Children
Authors: Garnett S. , Cowell C.T. , Bradford D. , Lee J. , Tao C. , Petrauskas V. , Fay R. , Baur L.A.
Published: April 2003

We investigated the relationship between IGF-I, gender, height, weight, body composition and birth size in 260 healthy 7- and 8-year-old children (139 females). All children were born term at Nepean Hospital, Western Sydney. Body composition was measured using dual energy X-ray absorptiometry. IGF-I levels were determined by radioimmunoassay. Girls had higher IGF-I levels than boys (20.2 ± 6.5 nmol/l compared to 15.9 ± 6.1 nmol/l, p < 0.001) but there was no correlation between age and IGF-I. IGF-I was positively correlated with height SDS (R2 = 0.12), weight SDS (R2 = 0.19), BMI SDS (R2 = 0.18), total body fat (%) (R2 = 0.14), and fat-free tissue/cm (R2 = 0.03). After adjusting for gender and current weight, IGF-I-levels were inversely related to birth size – children with the lowest birth size and heaviest current weight had the highest IGF-I levels. This correlation between birth weight and IGF-I supports the hypothesis that the IGF-I axis is altered in babies who are small for gestational age.
Tubercular Involvement of the Thyroid Gland: A Report of Two Cases
Authors: Orlandi Fabio , Fiorini Stefania , Gonzatto Ilaria , Saggiorato Enrico , Pivano Giovanni , Angeli Alberto , Pasquali Renato
Published: April 2003

Thyroid tuberculosis is rare. In the last decade, however, the incidence of extrapulmonary forms of tuberculosis has increased. We report on 2 cases of thyroid tuberculosis. In case 1, a tubercular abscess mimicking acute thyroiditis was found which was correctly diagnosed by fine-needle aspiration biopsy (FNAb). No evidence of active disease was noticed. Pleural thickening on chest X-ray was the only sign compatible with a previous infection. In case 2, tubercular thyroiditis with lymph node enlargement was also diagnosed by FNAb in a reevaluation setting. In both cases treatment with antitubercular drugs resulted in complete recovery. Thyroid tuberculosis should be kept in mind in the differential diagnosis of thyroid nodules, notably in patients with a history of tuberculous disease. FNAb represents the main approach to making the diagnosis.
Augmentative Effect of Polyethylene Glycol, Polyvinyl Alcohol and Dextran on Thyroid-Stimulating Antibody Stimulated cAMP Production in FRTL-5 Cells and CHO Cells Expressing Human TSH Receptor
Authors: Ochi Y. , Kajita Y. , Wu L. , Iidaka M. , Nagayama Y.
Published: April 2003

Previously we reported the augmentative effect of nonionic hydrophilic polymers such as polyethylene glycol (PEG), polyvinyl alcohol (PVA) and dextran on thyroid-stimulating antibody (TSAb) activity in porcine thyroid cell assays. We examined whether a similar phenomenon occurs in FRTL-5 thyroid cells and CHO cells expressing the human (h) TSH receptor (CHO-hTSHR cells). As with porcine thyroid cells, PEG 22.5% precipitated crude IgG from serum of patients with Graves’ disease, significantly increased cAMP production as compared with PEG 12.5% precipitated crude IgG in both FRTL-5 cells and CHO-hTSHR cells. PEG 5% augmented purified-TSAb-IgG-stimulated cAMP production in both cell assays. TSAb activities and positivity by the direct assay using whole serum (0.05 ml) in the presence of 5% PEG in untreated Graves’ patients were significantly increased as compared with the absence of 5% PEG. The augmentative effects of PVA 10% or dextran T-70 10% on TSAb-IgG-stimulated cAMP production were also observed in both cell assays. PVA 10% did not augment TSH-stimulated cAMP production in spite of weak augmentation by dextran 10% in both cell assays. Lack of the augmentative effects of PEG 5%, PVA 10% and dextran 10% on cAMP produced by GTPγS, forskolin and pituitary adenylate cyclase activating polypeptide was observed in both cell assays. The augmentative effects of these polymers in both cell assays similar to porcine thyroid cells suggest that there is no apparent species specificity among human, porcine and rat thyroid cells as far as TSH receptor linked cAMP production in cell membranes existed.
Volumetric Bone Mineral Density in Young Women with Turner’s Syndrome Treated with Estrogens or Estrogens plus Growth Hormone
Authors: Bertelloni Silvano , Cinquanta Luisa , Baroncelli Giampiero I. , Simi Paolo , Rossi Simona , Saggese Giuseppe
Published: April 2003

To explore the effects of estrogen replacement therapy (ERT) and recombinant growth hormone (GH) treatment on bone mineral density (BMD) in Turner’s syndrome, we assessed volumetric BMD (vBMD), which is less dependent on body and bone sizes, in these patients at final height. The areal BMD (aBMD) was measured in 26 young women with Turner’s syndrome (age range 17.5–25.0 years) by dual-energy X-ray absorptiometry, and vBMD was calculated. Patients were subdivided as group 1 (n = 12; ERT alone) and group 2 (n = 14; GH + ERT). Years of estrogen exposure were not different between the groups (group 1: 6.4 ± 1.5 years; group 2: 5.3 ± 1.7 years); in group 2, GH therapy was 5.3 ± 1.4 years. Final heights were significantly higher in group 2 than in group 1 (148.1 ± 3.0 vs. 142.0 ± 2.8 cm; p < 0.0001) as well as aBMD (1.073 ± 0.118 vs. 0.968 ± 0.122 g/cm2; p < 0.04). vBMD was higher in group 2 but not significantly different from group 1 (0.374 ± 0.030 vs. 0.358 ± 0.027 g/cm3; p = 0.169). aBMD was reduced with respect to the normative values in both groups (group 1: –1.97 ± 1.04 SDS, p < 0.0001 vs. 0; group 2: –0.93 ± 1.01 SDS, p < 0.005 vs. 0), whereas vBMD was not (group 1: –0.07 ± 0.79 SDS; group 2: 0.42 ± 0.82 SDS). Our data suggest that: in Turner’s syndrome GH administration improves final height and aBMD, but it does not significantly increase vBMD; aBMD reduction in Turner’s syndrome is likely due to the impaired growth and reduced bone size; Turner’s patients on ERT from adolescence show vBMD values in the normal range in young adulthood.