bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue Plasminogen Activator Administration Does Not Result in Clinically Relevant Neuropsychological Dysfunction in Patients with Myocardial Ischemia
Authors: Gomez Beldarrain Marian , Ruiz de Velasco Ivone , Garcia-Monco Juan C.
Published: April 2003

Background: Recent evidence from animal models has demonstrated that tPA can be neurotoxic to the hippocampus and cerebellum. Since tPA is used in patients with myocardial infarction and has been approved for the treatment of acute ischemic stroke, we carried out a pilot study to investigate whether its administration could result in any clinically relevant neuropsychological dysfunction, with particular attention to those structures most involved in the animal model. Patient and Methods: Patients with acute myocardial infarction (AMI) who were subjected to thrombolysis with r-tPA and without evidence of prior or concomitant neurological-neuropsychological damage, were eligible. Controls consisted of patients with AMI not candidate for thrombolysis or patients with severe angina admitted to the intensive care unit. A detailed neurological and neuropsychological evaluation was performed, which included mood, visual and verbal memory, psychomotor speed processing and motor dexterity and visuomotor sequence learning. Results: Ten patients and 13 controls were included. No significant differences between both groups were found, although all the subjects performed in the lower limits of the normal range on the Purdue pegboard test (motor dexterity) and digit-symbol test (psychomotor speed). There was no evidence of depression, as assessed by the Hamilton scale, that could have interfered with performance. Declarative memory (Rey auditory-verbal learning test) as well as visual memory (Rey-Osterrieth figure copy) and visuomotor sequence learning (serial reaction time task) were normal, without between-group differences. Conclusions: tPA administration at the usual doses did not result in detectable neuropsychological abnormalities in patients with myocardial ischemia.
Palmar Erythema: Cutaneous Marker of Neoplasms
Authors: Noble J.P. , Boisnic S. , Branchet-Gumila M.C. , Poisson M.
Published: April 2003

Background: Acral erythema on the palms is observed in several conditions. However, the relationship with malignant tumors has only been reported exceptionally. It should be noted that tumors produce angiogenic mediators. Objective: These mediators might promote palmar erythema (PE), and the aim of the present study was to investigate the vasodilation of palmar skin capillaries and angiogenesis, mainly with tumors of the central nervous system. Methods: In a prospective study of 107 patients affected by brain tumors, we assessed PE clinically and the rate of dilated vessels histologically. We also evaluated the mean surface of the lumen of capillaries on skin biopsies and brain tumors. Results: 6.5% of the patients had an important erythema and 18.5% had slight and/or localized PE. In the skin biopsies, the rate of dilated vessels and the mean surface of the lumen of capillaries were higher than in normal skin. Moreover, the intensity of palmar redness was related to the increase in these vascular changes in the histopathological slices of brain tumors. The intensity also depended on the type of tumor and on its growth. Conclusion: The results of the present study strongly suggest that acral erythema is associated with malignant tumors and that the intensity of erythema and the vascular changes of brain tumors are related, probably due to angiogenic factors.
Sectio nach Wunsch oder elektive Sectio: Aufforderung zum Umdenken
Authors: Haller U. , Hepp H. , Winter R.
Published: April 2003

Mortalität und Morbidität der Sectio, insbesondere des elektiven Kaiserschnittes, zeigen heute kaum mehr Unterschiede zur vaginalen Geburt. Die «Sectio nach Wunsch» oder «Wahlsectio» ist so extrem selten, dass sie keine Bedeutung erlangt und die Begriffe auch nicht verwendet werden sollten. Ein Umdenken muss deshalb stattfinden, weil ausnahmslos reale Befürchtungen die Schwangere zu einem solchen Schritt motivieren. Die zunehmende Gewichtung der Autonomie und das Recht auf Selbstbestimmung der Frau führen in diesem Zusammenhang zu einer grundlegenden Veränderung der Arzt-/Patienten-Beziehung. Langzeitfolgen nach vaginaler Geburt, wie Verletzung des Beckenbodens mit funktioneller Beeinträchtigung sowie Störungen der Sexualfunktion, aber auch Überlegungen zur Sicherheit des Kindes gewinnen für die Schwangere zunehmende Bedeutung und müssen von ärztlicher Seite ernst genommen werden. Obwohl genaue Berechnungsgrundlagen nicht vorliegen, wird ein globaler Kostenvergleich zwischen einer vaginalen Geburt und einer elektiven Sectio mit Berücksichtigung der Langzeitfolgen kaum eigentliche Unterschiede aufweisen, weshalb es für die Versicherer keine Berechtigung gibt, die Kostenübernahme zu verweigern.
Sectio nach Wunsch – Muss man hinsichtlich der Morbiditätsrisiken umdenken?
Authors: Schneider K.T.M.
Published: April 2003

Mütterliche und kindliche Morbiditätsparameter von 296916 Spontangeburten wurden mit 14883 elektiven Sectioentbindungen jeweils in einem Niedrigrisikokollektiv aus Daten der Bayerischen Arbeitsgemeinschaft für Qualitätssicherung verglichen. Die Kurzzeitmorbidität bei der elektiven Sectio (Wunschsectio) war für die Mutter als relativ gering einzustufen. Die grössten Unterschiede bei den schweren Komplikationen fanden sich in Form von Plazentalösungsstörungen, die bei der primären Sectio offenbar viel häufiger durch ein aktives Management vermieden werden können. Dagegen treten passagere Atemanpassungsstörungen bei Neugeborenen häufiger auf. Die gefürchteten Langzeitfolgen bei einer Sectio, wie Auftreten einer Plazenta accreta/increta mit entsprechenden Blutungsrisiken, treffen angesichts der rückläufigen Geburtenzahlen für die meisten Frauen nicht zu.
Longitudinal Assessment of Pituitary-Thyroid Axis and Adrenal Function in Preterm Infants Raised by ‘Kangaroo Mother Care’
Authors: Weller Aron , Rozin Aviram , Goldstein Abraham , Charpak Nathalie , Ruiz-Pelaez Juan G. , Figueroa de Calume Zita , Charpak Yves , Sack Joseph
Published: April 2003

Objective: To assess whether complete kangaroo mother care (KMC), a skin-to-skin contact intervention, would affect longitudinal/developmental patterns of hormonal change. Method: An open randomized controlled trial was conducted in a large tertiary care hospital, comparing KMC and traditional care for newborn infants weighing less than 2,001 g. Eighty-seven healthy preterm (<37 weeks gestational age) infants from this study provided three blood-spot samples on filter paper: at randomization (postnatal age 1–5 days), 2 weeks later, and at calculated term (41 weeks gestational age). They met a number of additional inclusion criteria including discharge from the hospital within the first postnatal week. The levels of 17α-hydroxy-progesterone (17-OHP), thyroxine-stimulating hormone (TSH) and thyroxine (T4) were assessed by radioimmunoassay. Birth weight (<1,800 or ≧1,800 g) and prenatal maternal corticosteroid treatment were taken into account in the analysis. Interventions: Complete KMC includes early discharge, positioning the infant on the parent’s chest in an upright position, 24 h/day in skin-to-skin contact, and breast-feeding. In the traditional care group, infants were discharged according to routine hospital practice. Results: Levels of 17-OHP and TSH decreased significantly from eligibility to calculated term while T4 levels did not change significantly over time. Most importantly, overall, treatment (KMC) did not interact with the pattern of physiological change. Conclusions: Maturation of the pituitary-thyroid axis and adrenal function is apparently not compromised by KMC, at least in healthy preterm infants.
Expression of the Gene for the Alpha-Subunit of Inhibin in Human Adrenocortical Tumours
Authors: Rich N. , Gaston V. , Le Bouc Y. , Gicquel C.
Published: April 2003

Background: To determine whether the pathogenesis of human adrenocortical tumours is associated with variations of inhibin expression, we assayed the mRNA of the α-subunit of inhibin in 5 normal adrenals and 48 adrenocortical tumours, including 10 paediatric tumours. Results: mRNA of α-subunit of inhibin was detected in all adrenocortical tissues. It was similarly abundant in the three pathological groups of adult tumours (benign, suspect and malignant) and in normal adrenal tissues, irrespective of the hormonal pattern. However, in paediatric tumours, the levels of the mRNA for the α-subunit of inhibin were significantly higher than those in adult tumours (p < 0.01). Conclusion: Inhibin is more abundant in the foetal than in the adult adrenal cortex and therefore these data suggest that the paediatric tumours may have a foetal pattern.
Molecular Genetics of Vitamin D- Dependent Hereditary Rickets
Authors: Kato Shigeaki , Yoshizazawa Tatsuya , Kitanaka Sachiko , Murayama Akiko , Takeyama Ken-ichi
Published: April 2003

Vitamin D exerts a wide variety of biological actions. The active form of vitamin D, 1α,25(OH)2D3, is biosynthesized from cholesterol. The final, critical step in this biosynthesis is conversion from 25-hydroxyvitamin D3 to 1α,25(OH)2D3 by the enzyme 25-hydroxyvitamin D3 1α-hydroxylase(CYP27B1)[1α(OH)ase]. 1α,25(OH)2D3 transcriptionally controls the expression of a particular set of target genes mediated through nuclear vitamin D receptor(VDR) acting as a ligand-inducible factor. Two types of vitamin D-dependent hereditary rickets (VDDR) are known to be caused by mutations in the 1α(OH)ase and VDR genes. The 1α(OH)ase gene is responsible for VDDR type I, and VDR for type II. Both of the diseases display an autosomal-recessive trait, but clinical features and response to administrated 1α,25(OH)2D3 are distinct. The phenotypes of the gene KO mice deficient of 1α(OH)ase and VDR exhibited the clinical abnormalities observed in the VDDR patients.
Genetic Alterations in Microsatellite Marker Sites among Tumor Suppressor Genes in Endometriosis
Authors: Nakayama Kuniaki , Toki Toshihiko , Nikaido Toshio , Zhai Ya-Li , Konishi Ikuo
Published: April 2003

Four endometriotic lesions were examined for the presence of genetic alterations in microsatellite marker sites among eight tumor suppressor genes. For this, a microdissection method was used on paraffin sections. Only one instance of loss of heterozygosity was detected at the PTCH locus. Heterozygosity was retained (indicating the absence of both loss of heterozygosity and microsatellite instability) at the other seven tumor suppressor gene loci in all the cases. Among the tumor suppressor genes examined, genetic defects in these microsatellite regions are certainly not ubiquitous in endometriosis and may be uncommon.
Factors Affecting Onset of Puberty
Authors: Delemarre-van de Waal Henriette A. , van Coeverden Silvia C.C.M. , Engelbregt Mia J.T.
Published: April 2003

In humans, foetal and early postnatal growth failure may have persistent consequences for growth and pubertal development in later life. During this period, the developing organs are still plastic to change their function, which may have long-lasting effects. At the time of onset of puberty, acute factors may also interfere with pubertal development. Malnutrition, as seen in anorexic patients, and chronic diseases with malabsorption or diseases with systemic effects result in a delayed onset of puberty. We have observed an earlier onset of puberty in girls with low birth weight; menarcheal age also tended to be earlier. In boys, a low birth weight tended to be associated with a later development. Two rat models with growth failure based on perinatal malnutrition have been examined, one with intrauterine growth retardation (IUGR) by ligation of the uterine arteries and one with postnatal food restriction (FR) by increasing the litter size postnatally. In both models, the rats had a persistent postnatal growth failure. The onset of puberty in female rats, defined by vaginal opening, was delayed only in the IUGR group. Despite a significantly lower weight, there was no difference in the timing of puberty onset in the FR group. In IUGR rats, the ovaries had fewer follicles, while FR rats had a normal number of follicles but an abnormal maturation pattern. In male rats, both models showed a delayed onset of puberty, defined by the balano-preputial separation, as well as impaired testicular function, shown by decreased testosterone levels. These data indicate that early malnutrition during a critical developmental time window may have long-lasting effects on pubertal development, including gonadal maturation in both humans and rats.
Pathogenesis of Precocious Puberty in Hypothalamic Hamartoma
Authors: Jung Heike , Ojeda Sergio R.
Published: April 2003

Astroglial-derived factors, as transforming growth factor (TGF)α and TGFβ, act in the hypothalamus to activate luteinizing hormone-releasing hormone (LHRH) secretion. Hypothalamic hamartomas (HHs) contain normal nervous tissue in a heterotopic location. When symptomatic, they cause precocious puberty and/or characteristic gelastic seizures. Thus far, the pathogenesis of these alterations remains unknown. By examining two HHs associated with sexual precocity, we found that they contained astroglial cells expressing TGFα, but no LHRH neurons. In a third patient with HH, only epilepsy was present, but precocious puberty developed shortly after surgery, probably as a consequence of a surgery-induced lesion. These results imply that some HHs induce sexual precocity by activating endogenous LHRH secretion via astroglial-derived factors.
Puberty in Chronically Diseased Patients
Authors: Simon Dominique
Published: April 2003

Delayed onset of puberty and a reduced pubertal growth spurt are often reported in patients suffering from chronic diseases. The basis of abnormal puberty in these patients is multifactorial. Nutritional deficiency may contribute to growth disorders and delayed puberty. Insufficient food supply and/or eating disorders and/or malabsorption of nutrients can be observed in these patients. Moreover, increased energy supplies are often needed in patients with chronic lung disease, infection or inflammation. More specific factors due to the disease itself may be involved in growth and puberty disorders. Abnormalities of the growth hormone (GH)-insulin-like growth factor (IGF)1 axis and gonadotrophin secretion have been described in patients with chronic renal failure, cystic fibrosis and Crohn’s disease. More recently, it has been shown that cytokines produced during chronic diseases such as juvenile idiopathic arthritis may affect the GH-IGF1 axis. Finally, concomitant medication, namely corticosteroids, which are often given to these patients, may contribute to delayed puberty and poor pubertal growth.
Mechanisms of Abnormal Puberty in Coeliac Disease
Authors: Bona Gianni , Marinello Daniela , Oderda Giuseppina
Published: April 2003

Coeliac disease (CD) is one of the most frequent chronic diseases in childhood. The clinical spectrum has changed; in addition to the classical gastrointestinal form, other clinical manifestations have been described, such as hypogonadism and the consequent delay in onset of puberty. Recent studies reported not only a significantly retarded menarche in untreated CD girls as compared with girls following a gluten-free diet, but also in treated CD a negative effect on pregnancy, resulting in lower birth weight and shorter duration of pregnancy. In boys, there is a reduced serum level of dihydrotestosterone and an increased serum level of luteinizing hormone, an abnormality pattern suggesting androgen resistance. The pathogenesis of CD-related reproductive disorders is still unclear. Some hypotheses may be tried; for example, in CD there is a high level of autoantibodies directed against self-antigens, so there could be antibodies directed against hormones or organs critical for pubertal development. Moreover, in CD there could be a selective malabsorption of micronutrients essential for the metabolism of carrier or receptor proteins for sex hormones.
Fibrous Dysplasia
Authors: Schoenau Eckhard , Rauch Frank
Published: April 2003

Definition: Fibrous dysplasia (FD) of bone is a non-inheritable congenital disorder affecting both genders. It is characterized by expanding fibrous lesions, which contain bone-forming mesenchymal cells. Pathophysiology: FD is caused by a somatic activating mutation of the alpha subunit of the Gs protein (Gsα). Bone mesenchymal cells produce a matrix of randomly distributed collagen fibres and islands of woven bone. Osteoclasts are responsible for the spread of the lesions. Clinical Findings: The symptoms are bone pain, fracture, bone deformities and neurological deficits. Spontaneous regression of lesions does not occur. Treatment: Recently, an observational study of treatment with bisphosphonate has yielded promising results. There was a decreased intensity of bone pain, a decrease in biochemical markers of bone turnover and a radiographically apparent ‘refilling of osteolytic sites’ in about half of the patients. Conclusions: Very little is known about the effects of bisphosphonate treatment in children and adolescents with FD. Most patients report decreased bone pain after the first pamidronate infusion, which, in our view, justifies the use of this drug in severely affected patients. The many unanswered questions regarding this form of treatment can only be addressed when a large number of patients is treated in a standardized fashion, and data on the outcome are collected.
Amplitude of Pubertal Growth in Short Stature Children with Intrauterine Growth Retardation
Authors: Lienhardt Anne , Carel Jean-Claude , Preux Pierre-Marie , Coutant Régis , Chaussain Jean-Louis
Published: April 2003

Objective: Pubertal growth contributes to 15–18% of adult height. A blunted pubertal peak could contribute to short adult height in short children born with intrauterine growth retardation (IUGR). Design and Methods: Pubertal growth, from onset of puberty to final height, was investigated in 75 short IUGR children: 47 were treated with recombinant human growth hormone (GH) (tx) before pubertal onset (mean dose: 0.4 IU/kg/week); 28 were not treated (no-tx). They were compared with 98 normal children. Results: Puberty occurred later in IUGR children than in controls (boys 14.2 ± 1 years vs. 12.1 ± 0.8 years; girls 12 ± 1 years vs. 11.2 ± 0.8 years; p < 0.0001). In girls, total pubertal growth was similar in all three groups (tx: 19.3 ± 4.8 cm; no-tx 19.8 ± 4.9 cm; controls 20.2 ± 3.9 cm; non-significant). IUGR boys had a reduced pubertal growth (tx: 21.3 ± 6.2 cm; no-tx: 23.9 ± 6.1; controls 26.9 ± 3.9 cm; p < 0.05). The age at puberty onset was the major determinant of pubertal growth amplitude (boys: r = 0.53, p < 0.001; girls: r = 0.45, p < 0.001). IUGR children exhibited little catch-up growth during puberty. Conclusions: In the present study, we describe a delayed onset of puberty in short children born with IUGR. Moreover, prepubertal GH treatment was associated in boys with a decrease in the amplitude of the pubertal spurt, a finding that should be further evaluated in clinical trials.
Learning from Leprosy: Insights into Contemporary Immunology from an Ancient Disease
Authors: Modlin Robert L.
Published: April 2003

Leprosy provides an ideal model to study immune responses in humans and in skin. Learning from leprosy, we have gained insight into mechanisms of host resistance and susceptibility to infection. New paradigms include the role of Th1/Th2 cytokines, the ability of CD1 to present nonpeptide antigens to T cells, the ability of microbial lipoproteins to stimulate antimicrobial activity in monocytes and the demonstration that T cells can mediate a direct antimicrobial activity through release of granulysin. Together, these findings provide a rationale for developing new strategies to treat and prevent infectious disease.
Molecular Studies of Hair Cell Development and Survival
Authors: Ryan Allen F.
Published: April 2003

The development of hair cells in both the auditory and vestibular sensory epithelia is a complex process that involves the coordinated expression of many regulatory proteins. Among these is the POU-domain transcription factor Brn-3.1. This factor is expressed in hair cell precursors immediately after commitment to the hair cell fate, and continues throughout life. Deletion of this factor in mice leads to failure of hair cell differentiation during development, and to the death of a majority of the undifferentiated cells. Normal expression of Brn-3.1 is required for adult hair cell survival as well, since a mutation in this gene causes dominant, late-onset, inherited hearing loss in humans. The timing of the onset of Brn-3.1 expression suggests that factors regulating its expression may be involved in fate determination of hair cells. Moreover, genes that are themselves directly regulated by Brn-3.1 appear to play critical roles in hair cell development and survival.
Stress Pathways in the Rat Cochlea and Potential for Protection from Acquired Deafness
Authors: Altschuler Richard A. , Fairfield Damon , Cho Younsook , Leonova Elena , Benjamin Ivor J. , Miller Josef M. , Lomax Margaret I.
Published: April 2003

Noise overstimulation will induce or influence intracellular molecular pathways in the cochlea. One of these is the ‘classical’ stress response pathway involving heat shock proteins. Hsp70 is induced in the cochlea by a wide variety of stresses including noise, hyperthermia and ototoxic drugs. When a stress that induces Hsp70 is applied to the cochlea, there is protection from a subsequent noise that would normally cause a permanent hearing loss. An upstream regulator of heat shock protein transcription, heat shock factor 1, is expressed in the cochlea and activated by stress. Mice lacking this heat shock factor have reduced recovery from noise-induced hearing loss. The same noise exposure that induces Hsp70 also increases the level of glial cell line-derived neurotrophic factor in the cochlea. Moreover, when this neurotrophic factor is applied into the perilymph of scala tympani prior to a noise exposure there is a significant reduction in hair cell loss and hearing loss. With the potential for activation of multiple pathways in the response to noise, gene microarrays can be useful to examine global gene expression. Initial studies examined differential gene expression immediately following a mild noise exposure (from which there is complete recovery) versus an intense noise (giving profound permanent deafness). Differential expression of several immediate early genes was found following the intense but not the mild noise exposure.
Potential Role of Purinergic Signalling in Cochlear Pathology
Authors: Thorne Peter R. , Munoz David J.B. , Nikolic Pedrag , Mander Lloyd , Jagger Daniel J. , Greenwood Denise , Vlajkovic Srdjan , Housley Gary D.
Published: April 2003

Adenosine triphosphate (ATP) is a major intercellular signalling molecule that is involved in neurotransmission in the central and autonomic nervous systems, regulation of blood flow, and neuroendocrine function. It is also a key signalling molecule involved in normal cochlear homoeostasis, regulating hearing sensitivity, controlling vascular tone and acting as a candidate neurotransmitter at the hair cell afferent synapses. It has also been established that extracellular ATP mediates some pathological processes such as inflammation, apoptosis and cell proliferation. Evidence for a profound influence of extracellular ATP on normal cochlear function offers the tantalising possibility that extracellular purine nucleotides may play a role in disease processes in the inner ear. This review draws on the current understanding of the pathophysiological role of extracellular ATP in tissues, and the evidence for the functional expression of purinergic signalling elements in the inner ear, to speculate on the potential role of purine nucleotides in cochlear pathology.
An Animal Model of Auditory Cortex Prostheses
Authors: Scheich Henning , Breindl Anette
Published: April 2003

Experiments aimed at rehabilitating deaf and blind patients with cortical prostheses were first conducted decades ago, but epicortical electrodes allowed only crude information transfer. Here we report that in Mongolian gerbils with electrodes implanted in input layers of the primary auditory cortex, spatial, temporal and spatiotemporal variations in intracortical stimulation all lead to perceptual differences as evidenced by discrimination training. For some stimulus regimes discrimination learning was as fast as with intracochlear stimulation in this animal. Intracortical stimulation induced field potentials and 2-deoxyglucose labeling patterns in primary auditory cortex similar to those induced by auditory click or tone stimuli, respectively. Given the common organization principles of neocortical areas, these results are presumably also of significance to prostheses interfacing with visual cortex.
Different Kinetics in Anti-Cytomegalovirus Immunity Reconstitution Evaluated by Lymphocyte Proliferation and IFN-γ Production in Allogeneic and Autologous Bone Marrow Transplantation
Authors: Mendes A.V.A. , Benard G. , Pereira C.B. , Kallas E.G. , Duarte A.J.S. , Pannuti C.S. , Dulley F.L. , Machado C.M.
Published: April 2003

Allogeneic bone marrow transplantation (ALLOBMT) is associated with an increased risk of cytomegalovirus (CMV) morbidity compared to autologous BMT (AUTOBMT). To investigate this, we evaluated AUTOBMT and ALLOBMT patients regarding anti-CMV immune reconstitution at 1 and 4 months after BMT and on the day after first CMV antigenemia detection. Intermittent ganciclovir preemptive therapy was prompted by antigenemia of ≧2 cells. One month after transplant, AUTOBMT recipients already displayed larger CD8+ T cell numbers than ALLOBMT recipients, but comparably small CD4+ T cell numbers. Most AUTOBMT patients had positive CMV antigen (CMV-Ag)-induced lymphoproliferation (86%) and IFN-γ secretion (86%), whereas this was infrequently seen in ALLOBMT patients (20 and 10%, respectively). This early AUTOBMT immune reconstitution was associated with a lower frequency of CMV reactivation up to +4 months in AUTOBMT (21%) than ALLOBMT patients (91%). At +4 months, most ALLOBMT recipients had also recovered CMV-Ag immune responses. At first antigenemia detection, all 3 AUTOBMT recipients already displayed anti-CMV immune functions and 2 cleared the infection without therapy, whereas of the 10 ALLOBMT recipients only 1 had positive lymphoproliferation. In the latter group, none had IFN-γ secretion or cleared the infection without therapy. Thus, differences in anti-CMV immune reconstitution may help to explain the contrasting rates of CMV morbidity between ALLOBMT and AUTOBMT patients.
Retinoic Acid Regulation of Mesangial Cell Apoptosis
Authors: Xu Qihe , Konta Tsuneo , Kitamura Masanori
Published: April 2003

Retinoic acid (RA) is recently used for the treatment of experimental glomerular diseases. However, mechanisms underlying its therapeutic effects are largely unknown. We recently reported that RA has the potential for protecting certain cells from particular injury. A typical example is its effect on oxidant-induced apoptosis of mesangial cells. Mesangial cells exposed to hydrogen peroxide undergo apoptosis through activation of the c-Jun N-terminal kinase activator protein 1 pathway. RA dramatically inhibits this process via suppression of c-fos/c-jun expression and inhibition of the c-Jun N-terminal kinase activation. The anti-apoptotic effect of RA is mediated by both nuclear receptor dependent and nuclear receptor independent mechanisms and is, at least in part, mediated by induction of mitogen-activated protein kinase phosphatase 1. In this review, we briefly summarize the current knowledge on molecular mechanisms involved in the anti-apoptotic effects of RA.
Matrix Metalloproteinases and Their Inhibitions in Experimental Renal Scarring
Authors: Johnson Timothy S. , Haylor John L. , Thomas Graham L. , Fisher Marie , El Nahas A. Meguid
Published: April 2003

Renal fibrosis is characterised by an excessive accumulation of extracellular matrix (ECM) proteins. Evidence suggests that this results from both increased ECM synthesis and a reduced degradation. Here, we determine changes in the matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) in relation to ECM production and the progression of renal fibrosis in subtotally nephrectomized (SNx) rats. Groups of 4–6 SNx or sham-operated male Wistar rats were sacrificed between days 7 and 120 following surgery. Total RNA was analysed by Northern blotting. Messenger RNA for collagens I (+710%), III (+674%), and IV (+358%) were significantly (p < 0.05) raised by day 7 and remained elevated over the 120 days. Significant (p < 0.05) increase in fibronectin, laminin and heparan sulfate proteoglycan mRNAs occurred latter at days 60 (+224%), 120 (+210%), and 120 (+256%), respectively. Increases (p < 0.05) in mRNA for MMP-1 (+360%) and MMP-2 (+239%) occurred from day 7 with MMP-1 reaching +881% by day 120. MMP-3 and -9 showed no change. Zymography on day 90 remnant kidneys showed mRNA changes were translated into active MMP-1 (+1,700%) and MMP-2 (+440%), p < 0.05. TIMP-1 mRNA was also raised (+548%, p < 0.05) by day 7 and remained elevated, while TIMP-2 mRNA levels only reached significance by day 120 (+165%). In contrast, TIMP-3 mRNA was decreased by day 30 (p > 0.05) and dropped to 27% of control by day 120. However, Western blot analysis of TIMPs 1 and 3 at day 90 showed a 5- and 4-fold increase respectively, while TIMP-2 levels were not significantly altered. Measurements of overall collagenase activities in remnant kidney homogenates were reduced. Using collagen I and IV substrates, proteolytic activity in remnant kidneys dropped to 40 and 27% of controls (p < 0.01), respectively. This data suggests that reduced MMP activity may contribute towards renal scarring, however this is not a result of reduced MMP transcription or activation, but likely to be due to the inhibition by TIMPs.
Nucleosome Effects on Mesangial Cell Matrix and Proliferation: A Possible Role in Early Lupus Nephritis
Authors: Coritsidis George N. , Lombardo Frank , Rumore Peter , Kuo Sheng Feng , Izzo Richard , Mir Rabia , Beers Philip
Published: April 2003

Background: Oligonucleosomes (ON) have been demonstrated in the circulation and biopsies of lupus nephritis patients. Their presence as immune complexes is an early and persistent finding in lupus nephritis as are changes in mesangial matrix. Since ON competitively bind to glomerular mesangial cells (MC) in a receptor-like fashion, the purpose of our study was to investigate what effects ON have on MC matrix and proliferation. Methods: Rat and mouse MCs grown with ON or DNA for 1 week were dissociated from their matrices with Triton-X and their proteins were determined. MC collagen production, using collagenase sensitive 3H-proline incorporation, was measured after 48-hour incubation with ON and DNA. Similar experiments using 10-fold excess DNA were done to assess its blocking effect on ON induced collagen synthesis. ON interaction with matrix was evaluated by incubated 125I-ON with MC matrix grown with ON or media alone for 1 week. Results: MCs stimulated by ON but not DNA significantly increased total matrix protein, total collagen and specifically, collagen type I synthesis. DNA inhibited ON-stimulated collagen synthesis. MC matrix incubated with ON binds 3 times more 125I-ON than matrix generated in media alone. Histone, a major component of nucleosomes, significantly increased 3H-thymidine incorporation. Conclusions: Oligonucleosomes, both qualitatively and quantitatively, influence mesangial cell function. These findings for the first time suggest ON to be pathogenic independent of their IC construct. DNA inhibition of ON induced mesangial matrix changes suggests participation of the ON/DNA receptor. Increased production of collagen type I may contribute to glomerulosclerosis.
The Identification of Renal Cell Carcinoma as a Target for Allogeneic Based Cancer Immunotherapy
Authors: Childs Richard W. , Igarashi Takehito
Published: April 2003

Renal cell carcinoma tumor cells are intrinsically resistant to chemotherapy, but unlike most solid tumors, may be susceptible to immune-based therapy. Because powerful immune effects can be generated against hematological malignancies following allogeneic stem cell transplantation, we investigated for similar anti-tumor responses in patients with metastatic renal cell carcinoma following the transplantation of an allogeneic immune system from a healthy HLA-matched family donor. Early laboratory and clinical results have demonstrated that following a reduced-intensity allogeneic stem cell transplant, donor T-cell mediated anti-tumor effects, resulting in sustained and sometimes complete tumor regression, can be generated against renal cell carcinoma (RCC) refractory to conventional cytokine-based therapy. Early data indicate that cytotoxic T cells of donor origin are the mediators of these anti-tumor effects. These preliminary studies provide additional evidence supporting the susceptibility of RCC to immune attack and lay the foundation for future targeted allo-immune-based cancer strategies.
Effects of Vitamin K2 on Bone of Ovariectomized Rats and on a Rat Osteoblastic Cell Line
Authors: Iwamoto Ichiro , Kosha Shoichiro , Fujino Toshinori , Nagata Yukihiro
Published: April 2003

The effects of vitamin K2 on bone mineral density (BMD) and bone metabolic markers of ovariectomized rats, and those on mRNA expression of osteocalcin and IL-6 on a rat osteoblastic cell line, were investigated. BMD and bone metabolic markers were examined in ovariectomized rats after 2 months’ treatment with vitamin K2, and mRNA expression of osteocalcin and IL-6 were measured in the cell line after 24-hour treatment with vitamin K2. Vitamin K2 attenuated the decline in BMD after ovariectomy in the rats, and suppressed serum deoxypyridinoline levels of the ovariectomized rats. No effect on osteocalcin and IL-6 mRNA expression on the cell line was observed. In conclusion, vitamin K2 has a bone-protective effect on ovariectomized rats.
Detection of the Cervical Gland Area in Threatened Preterm Labor Using Transvaginal Sonography in the Assessment of Cervical Maturation and the Outcome of Pregnancy
Authors: Yoshimatsu Kazuhiko , Sekiya Takao , Ishihara Kaisuke , Fukami Takehiko , Otabe Tohru , Araki Tsutomu
Published: April 2003

Objectives: To detect the cervical gland area in threatened preterm labor, and to determine its detection rate and relationship with cervical maturation and outcome of pregnancy in preterm labor. Methods: This was a mixed longitudinal and cross-sectional study involving 615 transvaginal scans performed to detect the cervical gland area and measure cervical length in 101 singleton pregnancies with threatened preterm labor. The patients were treated with intravenous administration of ritodrine chloride for regular uterine contractions at 16–35 weeks of gestation. 260 normal singleton pregnancies served as controls. Simultaneously conventional digital examination was used to assess the cervical maturation index. The detection rates of the cervical gland area, measurements of cervical length by sonography, and assessment of the cervical maturation index by digital examination in threatened preterm labor were compared with those of normal singleton pregnancies. In the threatened labor group, the outcome of pregnancy was assessed according to the sonographic absence or presence of the cervical gland area. Results: In the normal pregnancy group, the detection rate of the cervical gland area remained practically constant until the 31st week of pregnancy (97%), but substantially decreased thereafter (70.2% in gestational weeks 32–35). In the threatened preterm labor group, the detection rate of the cervical gland area was constantly lower (44.5%) and the cervical maturation index was higher (4.65 score) than in the normal pregnancy group (83.1% and 1.80 score, respectively). The outcome of pregnancy in the threatened preterm labor group was poorer in the subgroup with the absence of a cervical gland area than in the subgroup with the presence of a cervical gland area (duration of pregnancy 257.0 vs. 271.0 days, birth weight 2,597.2 vs. 2,990.0 g, and admission to delivery interval 38.8 vs. 60.8 days). Highly significant correlations were noted among the detection rates of a cervical gland area and cervical length, cervical maturation index, and outcome of pregnancy. Conclusions: This study demonstrates for the first time that the sonographic absence of the cervical gland area reflects cervical maturation and could be considered as a predictor of threatened preterm labor and a sign of poor outcome of pregnancy in this condition.
Q-Tip Test and Tension-Free Vaginal Tape in the Management of Female Patients with Genuine Stress Incontinence
Authors: Bakas P. , Liapis A. , Creatsas G.
Published: April 2003

Introduction: To compare the Q-tip test before and after performance of the tension-free vaginal tape (TVT) procedure in women with genuine stress incontinence, and to determine the value of the Q-tip test in order to predict the outcome of TVT. Methods: Thirty-one patients with a diagnosis of stress incontinence but without previous anti-incontinence surgery (group I) and 10 patients with stress incontinence and a history of previous anti-incontinence surgery (group II) participated in the study. None of these patients had an anterior vaginal wall prolapse of greater than stage I according to the International Continence Society Classification and, therefore, the TVT procedure was the only operation performed on these patients. Urethral mobility using the Q-tip test was assessed by the same examiner at the initial physical examination and at the 6-month follow-up examination. Cure was defined as no leakage of urine postoperatively either subjectively or objectively, while failure was defined the objective loss of urine during the stress test. Results: The mean preoperative and postoperative Q-tip measurement in patients without previous operation (group I) was 43.5 ± 5.84 and 33.38 ± 4.77(mean difference 10.12%. The mean preoperative and postoperative Q-tip measurement in patients with previous operation (group II) was 17.5 ± 4.44, and 11.1 ± 6.88°), while the cure rate was 40%. Conclusions: Adequate mobility of the proximal urethra is associated with a high success rate of the TVT procedure.
Growth Failure in Early Life: An Important Manifestation of Turner Syndrome
Authors: Davenport Marsha L. , Punyasavatsut Natavut , Stewart Paul W. , Gunther Daniel F. , Sävendahl Lars , Sybert Virginia P.
Published: April 2003

The goals of this study were to test the hypothesis that girls with Turner syndrome (TS) experience growth failure early in life and to establish model-based normative growth charts for 0- to 8-year-old American girls with TS. Full-term girls with TS who had 5 or more measurements of height obtained during their first 10 years of life prior to initiation of growth hormone, estrogen and/or androgen therapy were eligible for this study. A nonlinear mixed-effects model comprising the first two components of the infancy-childhood-puberty (ICP) model of growth was fitted to the longitudinal height measurements and compared with those of healthy American girls. Height measurements (n = 1,146) from 112 girls with TS (45,X: 57.1%; 45,X/46,XX: 12.5%; 46,X, iso(X): 4.5%, and other: 25.9%) were analyzed. Mean height SDS fell from –0.68 at birth to –1.60 at 1 year, –1.80 at 2 years and –1.95 at 3 years. When compared to controls (676 girls, 4,537 measurements), girls with TS grew more slowly due to three principal factors: a slow growth rate of the infancy component, a slow growth rate at the onset of the childhood component, and delayed onset of the childhood component. Traditional concepts of growth failure in TS should be revised. Physicians should consider the diagnosis of TS in any girl with unexplained failure to thrive or short stature, even in the first 3 years of life.
Ultrasonographic Assessment of Bone Maturity in Newborns
Authors: Leshem Eyal , Bialik Viktor , Hochberg Ze’ev
Published: April 2003

Background: Traditionally, the bone maturity at birth has been estimated from the radiological presence and size of the ossified distal femoral epiphysis. This study was conducted in a search for a sonographic tool for the evaluation of neonatal bone maturity. Methods: We examined sonographically 256 neonates within 24 h of birth. Gestational ages ranged from 36 to 42 weeks (mean: 39.4; median: 40). Birth weights ranged from 1,945 to 5,000 g (mean: 3,175; median: 3,180). The distal femoral epiphysis was imaged on the coronal plane sonogram of the distal femur with the knee at 90° flexion and the distal femoral epiphysis maximal height was recorded. The acetabulum was imaged using Graf’s method in the coronal plane image and the acetabular diameter recorded. Results: It was found that plotting the distal femoral epiphysis against neonatal birth weight and gestational age provided a simple method for assessing the bone maturity. According to our study, a neonate can be regarded as bone maturity percentile X when plotting distal femoral epiphysis height or acetabulum diameter against birth weight and gestational age or when averaging the four readings. Conclusions: We suggest performing sonography of the distal femoral epiphysis as a bedside tool for the assessment of skeletal maturity in newborns.
Effects of Tamoxifen on Lipid Profile and Coagulation Parameters in Male Patients with Pubertal Gynecomastia
Authors: Nóvoa F.J. , Boronat M. , Carrillo A. , Tapia M. , Díaz-Cremades J. , Chirino R.
Published: April 2003

Background/Aim: The estrogenic actions of tamoxifen on lipid profiles and hemostasis have been extensively demonstrated in women. Due to limited experience with this drug in males, it is uncertain whether these effects are also present in men. The aim of our study was to assess the response of blood lipids, lipoproteins, and coagulation parameters in a group of men taking tamoxifen. Methods: We studied 15 healthy boys with pubertal gynecomastia who were given 10 mg tamoxifen per day. Total testosterone, sex-hormone-binding globulin, estradiol, serum lipids, apolipoprotein B, apolipoprotein A-I, lipoprotein(a), fibrinogen, antithrombin III, von Willebrand factor, and markers of activated coagulation and fibrinolysis were determined at baseline and 1 and 3 months after beginning of the tamoxifen treatment. Results: Total cholesterol and lipoprotein(a) showed moderate but significant decreases from baseline. Low-density lipoprotein and high-density lipoprotein cholesterol concentrations as well as triglyceride and apolipoprotein B levels became lower, but these changes were not statistically significant. Among clotting parameters, antithrombin III was reduced, and von Willebrand factor increased significantly. Markers of activated coagulation and fibrinolysis remained unchanged throughout the period of therapy. Conclusions: The effects of tamoxifen on blood lipids and hemostasis we found in this group of healthy young men were qualitatively similar, but lesser than those previously described in women.
Ectopic ACTH Syndrome: Discrepancy between Somatostatin Receptor Status in vivo and ex vivo, and between Immunostaining and Gene Transcription for POMC and CRH
Authors: Kristiansen Mikkel T. , Rasmussen Lars M. , Olsen Niels , Asa Sylvia L. , Jørgensen Jens O.L.
Published: April 2003

Objective: To characterize somatostatin receptor status in vivo and ex vivo and immunoreactivity and gene transcription for proopiomelanocortin (POMC) and corticotropin-releasing hormone (CRH) in a case of Cushing’s syndrome caused by a sporadic metastatic medullary thyroid carcinoma (MTC). Methods:111In octreoscan, analysis of tumorous mRNA transcripts for somatostatin receptor subtypes (SSTR) as well as for POMC and CRH. Results: The tissue was intensely positive by 111In octreoscan but expressed only SSTR 1, 3 and 5. There was immunopositivity only for CRH, but gene transcription for both POMC and CRH was seen. Conclusions: (1) This first comparison between somatostatin receptor status in vivo and ex vivo in MTC shows a marked positive octreoscan despite absent SSTR 2 expression, and (2) this is the first report of a discrepancy between immunostaining and gene transcription for POMC and CRH.
Hospitalizations for Bacterial Endocarditis after Initiation of Chronic Dialysis in the United States
Authors: Abbott Kevin C. , Agodoa Lawrence Y.
Published: April 2003

Aims: Bacterial endocarditis is a significant cause of morbidity and mortality but has not been studied in a national population of end-stage renal disease patients. Methods: 327,993 dialysis patients in the United States Renal Data System initiated from 1 January 1992 to 30 June 1997 were analyzed in a historical cohort study of hospitalized bacterial endocarditis (ENDO, ICD9 Code 421.x). Renal transplant recipients were excluded. Results: Hemodialysis patients had an age-adjusted incidence ratio for ENDO of 17.86 (95% confidence interval, 6.62–48.90) and peritoneal dialysis patients 10.54 (95% CI, 0.71– 158.13, not statistically significant) compared to the general population in 1996 (the National Hospital Discharge Survey). 6.1% of patients with ENDO underwent valve replacement surgery. In multivariate analysis, hemodialysis (vs. peritoneal dialysis), earlier year of dialysis, cardiac disease, and lower serum creatinine and albumin were associated with increased risk of ENDO. In Cox regression analysis, patients with ENDO had increased mortality, relative risk 1.48 (95% CI 1.45–1.73). Conclusions: Patients on chronic dialysis were at increased risk for ENDO compared to the general population. The risk for peritoneal dialysis patients was not statistically significant, possibly due to the smaller numbers of patients on this modality. Hemodialysis (vs. peritoneal dialysis) and comorbidities were the strongest risk factors for ENDO identified.
New Acetylcholinesterase Inhibitor (Donepezil) Treatment for Alzheimer’s Disease in a Chronic Dialysis Patient
Authors: Suwata Junji , Kamata Kohzoh , Nishijima Tatsushige , Yoshikawa Tetsuo , Sano Motoki
Published: April 2003

The new-generation acetylcholinesterase inhibitor, donepezil, is useful in the treatment of mild-to-moderate Alzheimer’s disease. A 72-year-old male chronic hemodialysis patient was diagnosed as having moderate Alzheimer’s disease. We administered donepezil at 3 mg/day orally to the patient. After 1 month’s treatment, the patient improved to a controllable psychiatric condition and was discharged from the hospital. The 24-hour plasma concentration profile of donepezil following the 3-mg once-daily dose varied from 11.1 to 18.2 ng/ml. The through level of donepezil was reduced from 12.4 to 10.9 ng/ml over a 3-month period. We did not experience any episodes of drug toxicity or adverse effects in this chronic dialysis patient. Donepezil treatment might have a beneficial impact on patients with severe renal dysfunction.
Membranous Glomerulonephritis, Antiphospholipid Syndrome, and Persistent Low C3 Levels Associated with Meningococcal Disease
Authors: Bulucu Fatih , Can Cevat , Öktenli Çağatay , Koç Bayram , Polat Zülfikar
Published: April 2003

A young male patient with a recent history of meningococcemia was referred to our hospital in his recovery period. He had signs suggesting deep venous thrombosis in the legs but no other abnormalities on physical examination at admission. Laboratory results showed proteinuria (3.1 g/day), prolonged activated partial thromboplastin time (56.3 s), low level of C3c (0.19 g/l), high titers of both IgM (27.04 MPLU/ml) and IgG (74.88 GPLU/ml) anticardiolipin antibodies and recanalized thrombotic changes in the deep veins of the lower extremities on venography. Histopathological diagnosis of the kidney disease was membranous glomerulonephritis. He was started on an angiotensin-converting enzyme inhibitor to reduce proteinuria and an oral anticoagulant to prevent thromboembolic events. Since no reduction in proteinuria was observed at the 10th month of therapy, the angiotensin-converting enzyme inhibitor was discontinued. On his last follow-up, approximately 1.5 years after meningococcemia, he had no complaints and no abnormal findings on physical examination. While both IgM and IgG anticardiolipin antibody titers returned to the normal range, he still had persistent proteinuria and hypocomplementemia.