bluuebunny/crossref_metadata_2025 huggingface dataset:
New Aspects in Acne Inflammation
Authors: Toyoda Masahiko , Morohashi Masaaki
Published: April 2003

There is ample clinical evidence suggesting that the nervous system such as emotional stress can influence the course of acne. We examined possible participation of cutaneous neurogenic factors including neuropeptides, neuropeptide-degrading enzymes and neurotrophic factors, in association with inflammation in the pathogenesis of acne. Immunohistochemical studies revealed that substance P (SP)-immunoreactive nerve fibers were in close apposition to the sebaceous glands, and that neutral endopeptidase (NEP) was expressed in the germinative cells of the sebaceous glands in the skin from acne patients. Nerve growth factor showed immunoreactivity only within the germinative cells. In addition, an increase in the number of mast cells and a strong expression of endothelial leukocyte adhesion molecule-1 on the postcapillary venules were observed in adjacent areas to the sebaceous glands. In vitro, the levels and the expression of stem cell factor by fibroblasts were upregulated by SP. When organ-cultured normal skin specimens were exposed to SP, we observed significant increases in the sizes of the sebaceous glands and in the number of sebum vacuoles in sebaceous cells. Furthermore, supplementation of SP to organ-cultured skin induced expression of NEP, and we demonstrated the subcellular localization of NEP in the endoplasmic reticulum and the Golgi apparatus within the sebaceous germinative cells using preembedding immunoelectron microscopy. These findings suggest that SP may stimulate lipogenesis of the sebaceous glands which may be followed by proliferation of Propionibacterium acnes, and may yield a potent influence on the sebaceous glands by provocation of inflammatory reactions via mast cells. Thus, cutaneous neurogenic factors should contribute to onset and/or exacerbation of acne inflammation.
Measurement and the Newborn Infant
Authors: Gibson Alan T. , Carney Sally , Wright Neil P. , Wales Jeremy K.H.
Published: April 2003

Measurement of newborn babies is widely regarded as being too inaccurate to justify its regular practice. It is common for infants to be weighed at birth and for no other measurements to be made. Although such assumptions are superficially correct, it is possible to train people to perform accurate measurements and for improved performance to be sustained. Accurate sequential measurements are possible and provide more information than single measurements. Detailed measurements show that postnatal growth may change rapidly and dramatically, particularly in preterm infants. Postnatal growth impairment is common in such infants and may be sustained. Limited evidence suggests that there may be a significant reduction in final stature. Preliminary data also suggest that many preterm infants may also show evidence of alterations in biochemical and physiological variables consistent with early programming and the potential for altered disease susceptibility in adult life.
Coronary Heart Disease: A Disorder of Growth
Authors: Barker D.J.P.
Published: April 2003

A new ‘developmental’ model for the origins of coronary heart disease and the related disorders of type 2 diabetes, hypertension and stroke is emerging. The finding that people who develop these disorders have altered growth in utero, during infancy and childhood provides a new starting point for research. The immediate prospect for prevention is through protecting infant growth and preventing accelerated weight gain in children made vulnerable to later disease by small size at birth and during infancy. Ultimately we need to optimize maternal diet and composition before and during pregnancy. Despite current levels of nutrition in Western countries the nutrition of many fetuses and infants remains suboptimal because the nutrients available are unbalanced or because their delivery is constrained by the long and vulnerable fetal supply line.
Assays for Parathyroid Hormone and Their Use in Patients with End-Stage Renal Disease
Authors: Goodman William G.
Published: April 2003

New second-generation immunometric PTH assays have been developed. The assays measure full-length biologically active PTH(1–84) exclusively and do not detect amino-terminally-truncated PTH fragments, a feature that distinguishes them from first-generation immunometric PTH assays. Although few studies have been done thus far, second-generation immunometric PTH assays have not been shown to be superior to first-generation assays for the diagnostic assessment of patients with renal osteodystrophy. Plasma PTH levels obtained using first-generation-immunometric PTH assays continue to provide the most definitive guide to the management of renal bone disease because they are supported by abundant bone histology data. Additional work is needed to further characterize the utility of second-generation immunometric PTH assays as predictors of bone histology in patients with ESRD.
Slow Continuous Intracorporeal Plasmapheresis for Acute Fluid Overload
Authors: Handley Harold H. , Gorsuch Rey , Levin Nathan W. , Ronco Claudio
Published: April 2003

Intermittent dialysis is still the predominant treatment for acute or chronic renal insufficiency in the USA despite increasing evidence that slower and longer fluid management therapies are more beneficial to the patient. We have investigated the use of slow continuous intracorporeal plasmapheresis (SCIP) as a more efficient and hemodynamically stable alternative means of treating acute fluid overload. In this paper we discuss preliminary observations on the safety of SCIP catheter insertion, fluid removal, extraction and pathology in Yorkshire pigs. SCIP catheters removed plasma for extracorporeal plasma water removal without significant gross or histopathological changes. Blood chemistry and cell counts remained stable during therapy. Toxicological studies indicated no pyrogenicity, hemolysis, cytotoxicity, acute systemic toxicity, delayed-type hypersensitivity, or blood recalcification coagulation inhibition. Intracutaneous extracts caused only mild irritation. SCIP therapy appears to be safe for use in the removal of plasma and plasma water from experimental animals.
CA 125 and Vascular Endothelial Growth Factor in the Differential Diagnosis of Epithelial Ovarian Tumors
Authors: Candido dos Reis Francisco José , Moreira de Andrade Jurandyr , Bighetti Sérgio
Published: April 2003

Tumor markers have been investigated in differentiation of benign and malignant tumors. We analyzed CA 125 and vascular endothelial growth factor (VEGF) levels in serum and cyst fluid in patients with epithelial ovarian tumors. Serum and tumor cyst fluid of 50 patients with ovarian epithelial tumors (7 malignant, 3 bordeline and 40 benign) were assayed for VEGF by ELISA and CA 125 levels by chemoluminescence. CA 125 serum levels were significantly higher in patients with malignant and borderline tumors than in patients with benign cysts (p = 0.0005). CA 125 cyst fluid contents were comparable for malignant, borderline and benign ovarian tumors (p = 0.39). Significantly higher levels of VEGF were present in cyst fluid for malignant and borderline tumors compared with benign cysts (p < 0.0001); however, serum levels of VEGF were similar among all patients (p = 0.25). The CA 125 serum levels correlated with matched VEGF cyst fluid levels (r = 0.44, p = 0.0015). Serum CA 125 and cystic VEGF were good methods to differentiate benign and malignant epithelial ovarian tumors. Patients with elevated intracystic VEGF levels presented significantly higher CA 125 serum levels, although the CA 125 intracystic content overlapped. The angiogenesis and enhancement of vascular permeability induced by VEGF represents a new hypothesis for the release of the CA 125 antigen into the circulation in patients with ovarian epithelial neoplasm.
Serum Adenosine Deaminase Activity in Women with Pre-Eclampsia
Authors: Yoneyama Yoshio , Sawa Rintaro , Suzuki Shunji , Otsubo Yasuo , Miura Atsushi , Kuwabara Yoshimitsu , Ishino Hiroshi , Kiyokawa Yasuko , Doi Daisuke , Yoneyama Koichi , Kobayashi Hajime , Araki Tsutomu
Published: April 2003

The present study investigated serum adenosine deaminase (ADA) activity and the patterns of two ADA isoenzymes, ADA1 and ADA2, and to evaluate the possible role of cell-mediated immunity as causes of the changes in ADA activity in pre-eclampsia. We measured serum activities of total ADA, ADA1 and ADA2 in pre-eclampsia (n = 22) and normal pregnancy (n = 22). Peripheral blood monocyte counts and neopterin levels, reflecting the activation of the monocyte-macrophage cell system, were also measured. In pre-eclampsia, serum total ADA and ADA2 activities were significantly increased compared with normal pregnancy (p < 0.05), which were accompanied by increases in serum neopterin levels. These results suggest that increased total ADA activity reflects increases in ADA2 activity, which may be in part related to enhanced cell-mediated immunity during pre-eclampsia.
Expression of the P2X7 Receptor Subunit of the Adenosine 5’-Triphosphate-Gated Ion Channel in the Developing and Adult Rat Cochlea
Authors: Nikolic Predrag , Housley Gary D. , Thorne Peter R.
Published: April 2003

ATP-gated ion channels assembled from P2X7 subunits have been implicated in ontogeny and cellular pathology. Here, the expression of the P2X7 receptor subunit was studied in the embryonic (E14–E18 days) and postnatal (P0–adult) rat cochlea using immunohistochemistry. Strong P2X7 immunolabelling was observed in the primary auditory neurons of the spiral ganglion from E18 to adult and in the fibres innervating the sensory inner and outer hair cells from birth to adult. Strong immunolabelling of P2X7 receptor protein was also observed in the inner and outer hair cells over a limited developmental period, from birth to P6. Weak expression was observed in cochlear duct epithelium on E18 and in the supporting cells (footplates of pillar cells in adult and in Böttcher’s cells after birth). The immunolocalisation of P2X7 receptors further implicates extracellular ATP in signalling process in cochlear ontogeny and in establishment and function of auditory neurotransmission. The P2X7 receptors may be involved in signal transduction and modulation as well as in regulating cell death during development and in pathological conditions.
High-Frequency Sensitivity of the Mature Gerbil Cochlea and Its Development
Authors: Overstreet III Edward H. , Richter Claus-Peter , Temchin Andrei N. , Cheatham Mary Ann , Ruggero Mario A.
Published: April 2003

The thresholds of compound action potentials evoked by tone pips were measured in the cochleae of anesthetized gerbils, both in adults and in neonates aged 14, 16, 18, 20 and 30 days, using round-window electrodes. Stapes vibrations were also measured, using a laser velocimeter, in many of the same ears of adults and neonates aged 14, 16, 18 and 20 days to assess cochlear sensitivity in isolation from middle ear effects and to circumvent problems associated with calibration of acoustic stimuli at high frequencies. Whether referenced to sound pressure level in the ear canal or stapes vibration velocity, thresholds in adults were roughly uniform in the entire range of tested frequencies, 1.25–38.5 kHz. In neonates, thresholds decreased systematically as a function of age, with the largest reductions occurring at the highest frequencies. Thresholds remained slightly immature at all frequencies 30 days after birth. The results for adult gerbils are consistent with the recent finding that basilar-membrane responses to characteristic frequency tones normalized to stapes vibrations are as sensitive at sites near the round window as at more apical sites. The results for neonates confirm that the extreme basal region of the cochlea is the last to approach maturity, with substantial development occurring between 20 and 30 days after birth.
Virus-Like Particles as a Modular System for Novel Vaccines
Authors: Lechner Franziska , Jegerlehner Andrea , Tissot Alain C. , Maurer Patrik , Sebbel Peter , Renner Wolfgang A. , Jennings Gary T. , Bachmann Martin F.
Published: April 2003

Induction of protective immune responses with recombinant antigens is a major challenge for the vaccine industry. Here we present a molecular assembly system that renders antigens of choice highly repetitive. Using this method, efficient antibody responses may be induced in the absence of adjuvants resulting in protection from viral infection and allergic reactions.
Selective Expression of Immunogenic, Virus-Like Particle-Derived Antibody-Binding Epitopes
Authors: El Kholy Shereen , Riedl Petra , Kwissa Marcin , Reimann Jörg , Schirmbeck Reinhold
Published: April 2003

The incorporation of linear and conformational antibody-binding epitopes into polyepitope, chimeric antigens with satisfactory immunogenicity is a challenge. We selectively expressed antigen fragments encoding the linear e2 epitope (C79–149) of hepatitis B virus (pre)core antigen (HBc/eAg) and the conformational ‘a’ epitope (S80–180) of hepatitis B surface antigen (HBsAg) in a novel system. The domains were expressed as chimeric antigens containing either heat shock protein (hsp)73-binding simian virus 40 large tumor antigen (e.g. T77) or non-hsp-binding (e.g. T60) sequences at their N-termini. We compared their type of expression with their immunogenicity for B cells (when delivered as a DNA vaccine). The type of expression investigated included their level of expression, the secretion or intracellular expression of the antigen and the stress protein (hsp)-associated versus nonassociated expression. The linear e2 epitope of HBc/eAg was efficiently expressed as an intracellular, hsp73-binding fusion protein, and efficiently primed an HBc/eAg-specific antibody response when delivered in this form. The conformational ‘a’ epitope of HBsAg most efficiently stimulated B cells as a secreted, non-hsp-associated fusion protein. These data demonstrate that different B cell-stimulating epitopes of vaccine-relevant viral antigens can be selectively isolated and expressed in suitable expression systems, but that the requirements that have to be fulfilled to obtain optimal immunogenicity differ strikingly between individual epitopes.
Vaccine Development Using the Simian Immunodeficiency Virus Model for AIDS
Authors: Norley Stephen , Beer Brigitte , Binninger-Schinzel Doris , Vogel Thorsten , Hohn Oliver , Seibold Erik , Radke Dörte , Cosma Corina , Kurth Reinhard
Published: April 2003

Objective: A number of trials in primates using a wide range of putative vaccines based on simian immunodeficiency virus (SIV) have been performed and are summarised here. Methods: Rhesus macaques and African green monkey (AGMs) were immunised with the test vaccines and challenged with live virus to test the efficacy of the induced or transferred immune responses to protect from infection or disease development. Results: In initial studies, successful protection from challenge by whole inactivated virus vaccines was subsequently shown to be mediated by immune responses to human cell rather than viral proteins. Passive transfer of neutralising antibodies failed to protect against challenge. The induction of SIV-specific cytotoxic T lymphocytes (CTLs) using lipopeptides also failed to protect from infection, and whereas the frequency of post-infection CTLs (as measured by limiting dilution CTL assay and MHC/tetramer staining) correlated inversely with the cell-associated virus load, no correlation with the plasma virus load was observed. No immunological correlation of protection could be identified in macaques immunised with live attenuated SIV, with sterilising immunity being induced as early as 10 weeks after infection with the attenuated virus. Similarly, whole inactivated virus and passive IgG transfer failed to protect the natural host AGM species from challenge with apathogenic SIVagm, although live attenuated SIVagm afforded some protection despite the lack of overt vaccine virus replication. Conclusions: ‘Traditional’ types of vaccine are either ineffective or inappropriate for use in humans. Current efforts are therefore focusing on the rapidly evolving field of genetic vaccines based on vector DNA and recombinant, attenuated viral and bacterial vectors.
A Malaria Vaccine Candidate Based on a Hepatitis B Virus Core Platform
Authors: Sällberg Matti , Hughes Janice , Jones Joyce , Phillips Tom R. , Milich David R.
Published: April 2003

Objective: The recent success of a Plasmodium falciparum malaria vaccine consisting of circumsporozoite (CS) protein (CSP) T and B cell epitopes has rekindled interest in the development of a pre-erythrocytic vaccine. Our goal was to design an efficient delivery system for known neutralizing epitopes. Methods: Well-characterized CSP-specific neutralizing B cell epitopes and a ‘universal’ T cell epitope were combined with a particulate carrier platform, the hepatitis B core antigen (HBcAg), to produce a novel pre-erythrocytic vaccine candidate. Results: The vaccine candidate V12.PF3.1 is a potent immunogen in mice, eliciting unprecedented levels (greater than 106 titers) of sporozoite-binding antibodies after only two doses. The antisporozoite antibodies are long-lasting and represent all IgG isotypes, and antibody production is not genetically restricted. CSP-specific CD4+ T cells are also primed by V12.PF3.1 immunization in a majority of murine strains. Furthermore, the hybrid HBcAg-CS particles can be produced inexpensively in bacterial expression systems. Conclusion: These characteristics suggest that V12.PF3.1 represents an efficient and economical P. falciparum vaccine candidate for use separately or in combination with other formulations.
Effect of X-Irradiation on Growth and the Expression of Parathyroid Hormone-Related Peptide and Indian Hedgehog in the Tibial Growth Plate of the Rat
Authors: Bakker B. , van der Eerden B.C.J. , Koppenaal D.W. , Karperien M. , Wit J.M.
Published: April 2003

Aim: To study the effect of irradiation on the longitudinal growth and the expression of parathyroid hormone-related peptide (PTHrP) and Indian hedgehog (IHh) in tibial growth plates of rats. Methods: At 3 weeks of age, 30 male rats received a single fraction of irradiation (8 Gy) to their right hind limb, and small groups of animals were sacrificed 1, 2, 3, 5, 7, 10, 15, and 26 weeks after irradiation. Weight and length of both irradiated and nonirradiated tibiae were measured, and sections of the tibiae were stained with HE. PTHrP and IHh were visualized using immunohistochemical techniques. Results: Radiation resulted in persistent growth delay of the irradiated tibiae, with a difference in length of more than 10% between the irradiated and the nonirradiated tibiae 15 weeks or more after irradiation. The growth plate architecture was disturbed, and the expression of both PTHrP and IHh was decreased in the irradiated tibiae. Conclusion: As PTHrP and IHh are key regulators of both the pace and the synchronization of the differentiation of growth plate chondrocytes, the reduced expression of PTHrP and IHh may contribute to the changes found after irradiation.
Effects of Hypoxia and Thyroid Hormone on mRNA Levels and Activity of Phosphoglycerate Mutase in Rabbit Tissues
Authors: González-Cinca Nuria , Rivera Francisca , Carreras José , Climent Fernando
Published: April 2003

Aim: In the present work, we studied the effects of hypoxia and triiodothyronine (T3) on phosphoglycerate mutase (PGAM) activity and expression in rabbit liver, brain, and skeletal muscle under in vivo conditions. Methods: Hypoxia was induced in a methacrylate cage with a mixture of 90% nitrogen and 10% oxygen. Hyperthyroidism was induced daily by T3 injection (250 µg/kg). Results: Hypoxia increases the PGAM activity in liver and brain, tissues which possess type PGAM-BB isozyme, but does not affect the PGAM activity in muscle which possesses type PGAM-MM isozyme. T3 administration increases the PGAM activity in muscle and liver, but does not affect the enzyme activity in the brain. In all cases, the activity changes in parallel with those of PGAM mRNA levels. Conclusion: The tissue-specific effects of hypoxia and T3 could be explained by the tissue-specific distribution of both PGAM isozyme and T3 receptors.
Pattern of Bone Markers during Pregnancy and Their Changes after Delivery
Authors: Paoletti Anna Maria , Orrù Marisa , Floris Lucia , Guerriero Stefano , Ajossa Silvia , Romagnino Sandra , Melis Gian Benedetto
Published: April 2003

Objective: To investigate whether bone resorption markers change during pregnancy and lactation, and how they are correlated with human placental lactogen (hPL) and PRL. Subjects: Young women before pregnancy, during pregnancy and during a 12-month post-delivery period (study group; n = 22); and age- and weight-matched normal cycling women (control group; n = 22) for a 20-month-period participated in the study. Results: In the study group, women both during pregnancy (from the 8th up to the 38th week) and during a 6-month period of lactation, pyridinoline and deoxypyridinoline urinary levels were significantly higher than those of pre-pregnancy and control women. They returned to basal values at the 12th post-delivery month. During pregnancy there were early and late peak increases, at the 8th and 32nd week, respectively. At the 32nd, 34th, 36th and 38th week of pregnancy, pyridinoline and deoxypyridinoline urinary values were significantly correlated with hPL serum levels. Conclusions: During pregnancy the maternal bone resorption seems to vary critically at early and late stages. A complete reversal of these variations seems to occur after lactation. Further studies could evaluate if changes in placental function are capable of differently interfering with maternal bone resorption.
Familial Form of Thyroid Dysgenesis: Report of Thyroid Hemiagenesis with Accompanying Graves’ Disease in a Woman Whose Daughter Has Thyroid Agenesis
Authors: Lee I-Te , Sheu Wayne Huey-Herng , Lin Shih-Yi
Published: April 2003

The subject is a 44-year-old female with thyroid hemiagenesis, who initially presented with hyperthyroidism. Thyroid peroxide antibody and thyroglobulin antibody levels were high. The scintiscan study and sonographic findings were compatible with thyroid hemiagenesis with accompanying Graves’ disease. In reviewing her family history, her daughter was found to have thyroid agenesis, and other thyroid disorders were found in 2 female family members.
A Case of Turner Syndrome with Congenital Hypothyroidism Untreated until Age 38 Years
Authors: Ishikawa Norio , Tanaka Toshiaki , Hashimoto Kinya , Wada Masaki
Published: April 2003

Objective and Methods: The effect of thyroid hormone on human growth and maturation is considered ‘permissive’. To evaluate the effect of a prolonged thyroid hormone defect, especially in the pubertal period, a woman with untreated congenital hypothyroidism underwent studies of thyroid function and bone maturation for the first time at age 38 years 10 months and received thyroid hormone replacement. Results: The karyotype was 45,X/46,XX. Menstruation had occurred for 10 years, from menarche until she was about 31 years old. Epiphyseal closure of the left hand was incomplete. The serum thyroid hormone level was virtually undetectable, and her thyroid gland was not detectable in the normal position by ultrasonography. Her height increased by 3.5 cm in the first 9 months after starting thyroid hormone replacement; after 11 months, closure of the epiphysis was complete. Conclusion: Thyroid hormone is necessary to achieve bone maturation and epiphyseal closure, but its role is only permissive.
Low Birth Weight: Effect on Insulin Sensitivity and Lipid Metabolism
Authors: Jaquet Delphine , Léger Juliane , Lévy-Marchal Claire , Czernichow Paul
Published: April 2003

The metabolic and cardiovascular complications associated with reduced fetal growth have been identified during the past 10 years. These complications that encompass cardiovascular diseases and insulin resistance syndrome consist of dyslipidemia, impaired glucose tolerance or type 2 diabetes and appear to result from the initial development of insulin resistance. The association of reduced fetal growth with the other parameters of the syndrome X appear less constant than with insulin resistance and the expression and/or the age of onset seem to depend on the degree of genetic predisposition of the population. Although the mechanisms underlying the development of the insulin resistance associated with reduced fetal growth remain unclear, some evidence argues in favor of a key role of the adipose tissue. Several hypotheses have been proposed over the past 10 years to understand this unexpected association. Each of them points to either a detrimental fetal environment or genetic susceptibilities or interactions between these two components as playing a critical role in this context. Although not confirmed, the hypothesis suggesting that this association could be the consequence of genetic/environmental interactions remains at the moment the most attractive.
Effect of Global Hypoxia-Ischaemia followed by 24 h of Mild Hypothermia on Organ Pathology and Biochemistry in a Newborn Pig Survival Model
Authors: Satas S. , Løberg E.M. , Porter H. , Whitelaw A. , Steen P.A. , Thoresen M.
Published: April 2003

Background: Perinatal asphyxia may lead to multiorgan damage as well as brain injury. Posthypoxic hypothermia (HT) may protect other organs in addition to the brain. The aim of this study was to assess the systemic effects of our global hypoxic-ischaemic (HI) insult and compare the effect of mild 24-hour HT with normothermia (NT) during unsedated recovery. Method: Thirty-eight newborn pigs were subjected to 45 min of global HI by ventilating them with ∼6% O2. On reoxygenation, pigs were randomised to NT or HT. The 18 NT piglets were maintained at rectal temperature 39.0°C for 72 h. Twenty-three HT pigs (20 experimental HT and 3 sham controls) were cooled to rectal temperature 35°C for 24 h before NT was resumed and the animals then survived a further 48 h. Results: All lesions were small with no apparent clinical effect. The incidence of any damage to the heart (6 HT vs. 9 NT), liver (9 HT vs. 7 NT), kidney (6 HT vs. 9 NT) or intestinal injury (8 HT vs. 2 NT, p = 0.07) was not different in the two groups. More HT piglets developed lung injury, 10 HT and 3 NT. Plasma [Na], [K], [Ca] and [Mg] increased significantly after the HI insult as compared to baseline values. For the 24-hour period plasma [K] and [Ca] were significantly higher in the HT group, the mean area under the curve (AUC) being for [K] AUCHT 4.4 mmol/l vs. AUCNT 3.9 mmol/l, p = 0.04 and for [Ca] AUCHT 2.7 mmol/l vs. AUCNT 2.5 mmol/l, p = 0.01, respectively. Aspartate aminotransferase peaked at 48 h in the HT group and at 24 h in the NT group. Creatinine peaked at >72 h in the HT pigs and at 48 h in the NT pigs. White blood cells (WBC) peaked at 12 h for the HT pigs and at 6 h for the NT animals. AUC of the WBC during the cooling was significantly lower in the HT pig (AUCHT 11.1 vs. AUCNT 15.3 103/mm3, p = 0.04). The HT pigs needed more glucose to maintain normal glucose during the last 12 h of HT. Also HT animals needed more oxygen during cooling to maintain PaO2. Conclusion: Twenty-four hours of mild HT did not reduce damage in any organ. There was a slight increase in lung damage in the HT group. None of the biochemical or pathological changes were of clinical significance. We conclude that mild HT for 24 h does not affect the organ systems adversely when compared to NT. Additional glucose and oxygen is needed during cooling to maintain normal values.
Relationship between Cord Blood Level of IgE Specific for Dermatophagoides pteronyssinus and Allergic Manifestations in Infancy
Authors: Nambu Mitsuhiko , Shintaku Noriaki , Ohta Shigeru
Published: April 2003

The relationship between the cord blood level of IgE specific for Dermatophagoides pteronyssinus (Dp-IgE) and the development of allergic disorders in infants was investigated. None of the 10 infants who had no family history of allergic disorders and a cord blood Dp-IgE level of <0.07 IU/ml developed atopic dermatitis by 10 months of age. Among the infants whose mothers had atopy, those with a cord blood Dp-IgE level of ≧0.07 IU/ml showed a higher prevalence of allergic disorders at 3 years of age than those with a cord blood Dp-IgE level of <0.07 IU/ml. These observations suggest that the cord blood Dp-IgE level may be related to allergic manifestations in infancy.
Screening for Alzheimer’s Disease with the Short Cognitive Evaluation Battery
Authors: Robert Philippe H. , Schuck Stéphane , Dubois Bruno , Olié Jean Pierre , Lépine Jean Pierre , Gallarda Thierry , Goni Sylvia , Troy Sylvie
Published: April 2003

Because Alzheimer’s disease (AD) tends to be underdiagnosed, there is an increasing need for accurate neuropsychological screening tools that are easy to administer by general practitioners or specialists. The aim of the present study was to validate, in French, a sensitive and specific screening battery designed to improve the discrimination between patients with AD, patients with depression and healthy elderly subjects. The Short Cognitive Evaluation Battery (SCEB) consists of 4 brief tests: temporal orientation, 5-word test, clock-drawing test and a semantic verbal fluency task. The SCEB was administered to 123 ambulatory subjects (mean age 76.4±2.3 years): 49 patients with mild AD, 27 patients with depressive symptoms and 47 healthy elderly subjects. The mean time for administration of the test was 11.2 min in the AD group, 8.2 min in the depressive group and 7.2 min in the control group (p < 0.001). Multivariate analysis showed that, compared with controls, patients with mild AD were significantly impaired for all four tests. Response operating characteristics analysis of the SCEB showed: 93.8% sensitivity and 85% specificity for discriminating AD from control patients, and 63% sensitivity and 96% specificity for discriminating AD from depressive patients. In summary, the SCEB appears to be a highly sensitive and specific tool for discriminating between patients with mild AD and healthy elderly individuals. Furthermore, in combination with clinical evaluation, the SCEB could improve the specificity of the difficult discrimination between mild AD and depression.
Behavioral Problems in Dementia: A Factor Analysis of the Neuropsychiatric Inventory
Authors: Aalten Pauline , de Vugt Marjolein E. , Lousberg Richel , Korten Edith , Jaspers Niek , Senden Birgit , Jolles Jelle , Verhey Frans R.J.
Published: April 2003

The aim of this study was to detect behavioral subsyndromes of the 12-item Neuropsychiatric Inventory (NPI). Cross-sectional data of 199 patients with dementia living in the community were collected. Principal component analysis (with Varimax rotation) was used for factor analysis. Results showed the presence of three behavioral subsyndromes: mood/apathy, psychosis, and hyperactivity. Anxiety was regarded as a separate symptom. The subsyndrome mood/apathy was the most common, occurring in almost 80% of the patients, versus psychosis and hyperactivity, which occurred in 37 and 60% of the patients, respectively.
Lack of Association between Alzheimer’s Disease and Gln-Arg 192 Q/R Polymorphism of the PON-1 Gene in an Italian Population
Authors: Pola Roberto , Gaetani Eleonora , Flex Andrea , Gerardino Laura , Aloi Francesco , Flore Roberto , Serricchio Michele , Pola Paolo , Bernabei Roberto
Published: April 2003

Alzheimer’s disease (AD) is characterized by deposition of oxidized low-density lipoprotein (LDL) forming the senile plaque and by structural changes and cell death in acetylcholine-producing neurons. Paraoxonase-1 (PON-1) is a secreted protein primarily associated with high-density lipoproteins (HDL) and participates in the prevention of LDL oxidation. PON-1 is also an arylesterase that hydrolyzes paraoxon, an active toxic metabolite of parathion, thus providing protection against organophosphate poisoning and metabolization of environmental neurotoxins that might be responsible for neurodegeneration with aging. Serum levels of PON-1 are genetically determined and strongly influenced by a common polymorphism on the position 192 of the PON-1 gene. The aim of this study was to evaluate whether the polymorphism of the PON-1 gene is associated with AD. We studied 124 Italian subjects affected by probable AD and 135 age- and sex-matched controls. The distribution of PON-1 genotypes was 64 QQ, 46 QR, 14 RR in the AD patients and 57 QQ, 59 QR, 19 RR in the control subjects. No statistically significant difference was found between the two groups in our population (p = 0.130 for homozygous QQ, p = 0.279 for heterozygous QR, and p = 0.502 for homozygous RR). These results suggest that the human Gln-Arg 192 Q/R polymorphism of the PON-1 gene is not associated with AD in an Italian population.
MRI-Guided Frameless Stereotactic Percutaneous Cordotomy
Authors: McGirt Matthew J. , Villavicencio Alan T. , Bulsara Ketan R. , Gorecki John
Published: April 2003

Background: Use of intraoperative myelography as a radiologic guidance for percutaneous cervical cordotomy (PCC) has been superseded by more modern imaging. The only significant advancement in cordotomy techniques over the last 30 years has been CT-guided PCC. The goal of this study was to demonstrate the feasibility of an MRI-guided frameless technique in high cervical cordotomy. Methods: We describe 6 patients with intractable pain treated using a frameless, MRI-guided, stereotactic, PCC technique in combination with standard physiological localization procedures. Results were compared with those from 32 patients who underwent PCC in the last 5 years using physiological localizing techniques only. Results: Six patients (100%) who underwent the frameless technique had excellent pain relief postoperatively. Patients in the non-stereotactic group, on average, required a higher number of lesions (2.5 vs. 1.2, p < 0.005), and 7 (22%) of these patients had unsatisfactory pain relief following PCC (p = 0.21). Five patients in the non-stereotactic group had weakness postoperatively and 1 had changes in bladder function. Postoperative weakness occurred in 1 patient undergoing the frameless technique. At an average of 6 months of follow-up (range 5–11), excellent pain relief was achieved in 83% (5/6) of MRI frameless PCC patients and 55% (16/29) of standard PCC patients (p = 0.20). Conclusions: Intraoperative frameless stereotaxy provides surgeons with accurate information that helps to guide the operative approach and precisely tailor the trajectory and depth of the electrode, potentially increasing the safety and efficacy of the operation.
Nefazodone in Psychotic Unipolar and Bipolar Depression: A Retrospective Chart Analysis and Open Prospective Study on Its Efficacy and Safety versus Combined Treatment with Amitriptyline and Haloperidol
Authors: Grunze Heinz , Marcuse Alain , Schärer Lars O. , Born Christoph , Walden Jörg
Published: April 2003

Although atypical antipsychotics are on the rise, traditional treatment of psychotic (or delusional) depression mostly includes the addition of classical antipsychotics to antidepressants. As there are only few data supporting this approach compared with antidepressant monotherapy, and almost no data comparing it with antidepressants of the latest generation, we conducted a retrospective chart analysis and a prospective, randomized open study on the efficacy and tolerability of nefazodone monotherapy versus combined treatment with amitriptyline and haloperidol in psychotic depression. The results suggest that the addition of classical antipsychotics should be reserved for those with very severe psychotic symptoms, but may not be needed in milder forms.
Silent Cerebral Infarction in Hemodialysis Patients
Authors: Nakatani Tatsuya , Naganuma Toshihide , Uchida Junji , Masuda Chikayoshi , Wada Seiji , Sugimura Takeshi , Sugimura Kazunobu
Published: April 2003

Background: Cerebrovascular diseases are very common in hemodialysis (HD) patients. Silent cerebral infarction (SCI) has not been investigated in HD patients although it may be a significant risk factor for cerebrovascular diseases. Hypothesis: Chronic renal failure may be an independent risk factor for SCI and cerebrovascular diseases. Methods: Cranial magnetic resonance imaging (MRI) was performed on 123 HD patients without symptomatic cerebrovascular disease and on 52 control subjects. We investigated the prevalence of SCI and performed cross-sectional study using multiple logistic analysis to assess the relationship between SCI and the risk factors. Results: The prevalence of SCI was significantly higher in HD patients than in the healthy control group (60 patients (48.8%) vs. 5 patients (9.6%), χ2 = 22.4, p < 0.0001). Multiple logistic regression analysis with all subjects showed that independent risk factors of SCI were chronic renal failure, hypertension, smoking and age (R2 = 0.468, p < 0.0001). In only the HD patient group, age and smoking were shown to be independent risk factors of SCI (R2 = 0.378, p < 0.0001) while HD duration and hypertension were not. Conclusions: The findings of the present study indicate that chronic renal failure maintained by hemodialysis increases the prevalence of SCI and that age and smoking habits are also significantly associated with SCI in HD patients.
Primitive Neuroectodermal Tumor Arising in Long-Standing Cerebellar Atrophy
Authors: Bisson Erica , Florman Jeff , Wald Steven , Tranmer Bruce
Published: April 2003

Primitive neuroectodermal tumors (PNETs) account for one fifth of childhood brain tumors. Although little is known of the pathobiology of this tumor type, there are associations with both genetic syndromes and exposures to specific environmental agents. Progressive cerebellar atrophy predating the presentation of a primary brain tumor, in the absence of a genetic syndrome, has not been reported with PNETs. We report a case of a posterior fossa PNET occurring in association with long-standing cerebellar atrophy without evidence of a genetic syndrome. This case may represent an unrecognized paraneoplastic syndrome or a unique subtype of PNET.
Primary Excision of Pediatric Posterior Fossa Abscesses – Towards Zero Mortality?
Authors: Agrawal Deepak , Suri Ashish , Mahapatra Ashok Kumar
Published: April 2003

Nine children with infratentorial brain abscesses were treated at our institution over a 3-year period. Seven of them were boys and two were girls. In five cases, the abscesses were otogenic, and in two cases, the cause was tubercular (including one case of tubercular otitis). There were three cases of abscess formation in dermoids. All cases were managed with primary excision of the abscess. The average hospital stay was 12 days, and there was no mortality. The most common complication was hydrocephalus, noticed in three patients, of whom one eventually required shunt placement. Our policy of primary excision of these abscesses has yielded gratifying results. This approach also resulted in minimal morbidity and a substantially shortened hospital stay. Moreover, primary excision yields definitive histopathology of the lesion, especially in cases of tubercular and dermoid etiologies.
Successful Treatment of Supraventricular Tachycardia Exhibiting Hydrops fetalis with Flecainide Acetate
Authors: Nakata Masahiko , Anno Kikue , Matsumori Lena Tashima , Fujiwara Motoki , Sumie Masahiro , Sase Masakatsu , Kato Hiroshi
Published: April 2003

Background: The efficacy of flecainide acetate for the treatment of fetal supraventricular tachycardia with hydrops fetalis and changes in venous blood flow patterns in the fetus during treatment are reported. Case: Oral flecainide administration was started at 30 weeks of gestation. Cardioversion was achieved 6 days after treatment. Sustained abnormal venous Doppler indices were shown and complete normalization of venous returns was observed 6 days after cardioversion. A vigorous male baby was born, and he is now 1 year of age and in good condition with no medication. Conclusion: Reversible cardiac dysfunction was observed even after cardioversion in the fetus with supraventricular tachycardia, which could be assessed precisely by venous Doppler analysis.
A Case of Fetal Vesicoallantoic Cyst in the Umbilical Cord
Authors: Osawa Kazunori , Ito Mitsuhiro , Sugiyama Masahiko , Kanamori Yutaka , Hashizume Kohei , Marumo Genzo
Published: April 2003

A vesicoallantoic cyst in the umbilical cord was detected by fetal ultrasonography at 16 weeks of gestation. The blood flow through the umbilical vessels was evaluated with periodic color Doppler ultrasonographic examinations because compression by the cyst may cause reduction in blood flow and lead to fetal death. After disappearance of the cyst, the infant was delivered vaginally. Retrograde cystography revealed a narrow channel between the bladder and the navel, confirming patent urachus, which was resected without any complications.
Validation of Primed in situ Labeling for Interphase Analysis of Chromosomes 18, X, and Y in Uncultured Amniocytes
Authors: Mennicke Kirsten , Yang Jianbin , Hinrichs Frauke , Müller Andreas , Diercks Petra , Schwinger Eberhard
Published: April 2003

Objective: Primed in situ labeling (PRINS) is an interesting alternative to the traditional fluorescence in situ hybridization (FISH) for the in situ detection of specific sequences in chromosome anomalies. It combines the sensitivity and specificity of the polymerase chain reaction with the specific in situ signal detection capability of FISH. Methods: We performed PRINS on uncultured amniocytes and compared the results with standard cytogenetic analysis. In a prospective study, a total of 262 independent samples were analyzed for numerical aberrations of chromosome 18. Results: In more than 95% of the cases PRINS reactions were successfully achieved. Neither false-positive nor false-negative results were obtained. 62 of the 262 cases were in parallel examined for chromosome 18 aneuploidies by FISH. Although there were significant differences in signal distribution, these did not lead to a different overall classification of the respective cases, i.e., the end results of disomic and trisomic cases for chromosome 18 were identical between FISH and PRINS. In 205 of 262 cases PRINS was performed for chromosomes X and Y. 97.6% of these samples were properly sex differentiated. Conclusions: The PRINS assay is a simple and cheap alternative to detect numerical aberrations of chromosome 18. However, the rate of false-positive results for chromosome X was calculated as 1% and the rate of false-negative ones for chromosome Y as 2%. Further investigations are required to transform PRINS into an alternative to conventional methods for routine rapid prenatal diagnosis of gonosomes.
Comparison of Triple-Risk Assessment of Fetal Trisomy 21 Including Total Human Choriogonadotropin (hCG) or Its Free β-Subunit (Free βhCG)
Authors: Sancken U. , Bahner D.
Published: April 2003

Objective: Second trimester total hCG and free βhCG levels in maternal serum samples of 33 pregnancies affected by fetal trisomy 21 and of 188 matched controls were compared in a retrospective study. To find out differences of discriminating efficacy by using one of these markers a multivariate discriminant analysis was performed. Method: Statistical evaluation was performed for hCG/free βhCG frequency distributions. Discriminant analysis was carried out using the status ‘affected’ or ‘unaffected’ as the group variable and the serum markers unconjugated estriol (uE3), alpha-fetoprotein (AFP), and alternatively, hCG or free βhCG, as discriminant variables. Results: The median of free βhCG MoM values in affected pregnancies was slightly higher (1.90 MoM) than the median of total hCG MoM values (1.72 MoM) but a lower standard deviation was stated for the logarithmic hCG MoM values (SD = 0.49) compared with free βhCG MoM values (SD = 0.51). A two-tailed Student’s t test revealed no significant differences of hCG and free βhCG MoM values in both the affected and unaffected pregnancies. By inclusion of free βhCG the discriminant analysis classified 26 out of 33 affected cases correctly and 45 out of 188 unaffected cases incorrectly. For the inclusion of hCG these ratios were 25/33 and 41/188, respectively. Taking in account the individual maternal age risks at a defined false-positive rate of 5% including free βhCG yielded a higher detection rate than including hCG. However, using 1:380 (age-related at-term risk of a 35-year-old woman) as a cut-off risk including hCG yielded a higher detection rate than including free βhCG. Conclusion: For the observed cases none of the markers, hCG or free βhCG, was superior in Down syndrome screening.
History of Fetal Diagnosis and Therapy: Children’s Hospital of Philadelphia Experience
Authors: Hedrick Holly L. , Flake Alan W. , Crombleholme Timothy M. , Howell Lori J. , Johnson Mark P. , Wilson R. Douglas , Adzick N. Scott
Published: April 2003

Since its inception in 1995, the mission of the Center for Fetal Diagnosis and Treatment at the Children’s Hospital of Philadelphia (CHOP) has been to provide comprehensive, multidisciplinary expertise in all facets of prenatal diagnosis, reproductive genetics, and prenatal, perinatal, and postnatal treatment for abnormal fetuses. Most of the authors were trained and/or served on faculty at centers in San Francisco (N.S.A., A.W.F., T.M.C., L.J.H.) or Detroit (A.W.F, M.P.J.). Accurate prenatal detection by serial sonographic study and the development of ultrafast magnetic resonance imaging (MRI) scanners has permitted delineation of the natural history of anatomic malformations. Definition of the pathophysiological features that affect clinical outcome and formulation of management based on prognosis has allowed families to make informed decisions. Outcomes have been improved through carefully planned and coordinated perinatal management. In some cases of life-threatening or severely debilitating defects, prenatal surgery has been offered.
A Point Mutation in the First Splice Donor Leads to Reduced Oncogenic Properties of the Adenovirus Serotype 12 E1A Gene
Authors: Lehmkühler Oliver , Kühn Claudine , Gunawardena Bettina , Esche Helmut , Brockmann Dieter
Published: April 2003

Cells transformed by proteins of early regions 1A (E1A) and 1B (E1B) of oncogenic adenovirus serotype 12 (Ad12) grow to tumours in syngeneic, immunocompetent rodents. To gain insight into the mechanisms of oncogenic transformation, we point mutated the first splice donor in the Ad12-E1A gene, leading to the loss of the Ad12-E1A9.5S and Ad12-E1A11S/10S proteins and to a conservative amino acid (aa) exchange at position aa 30 (valine vs. leucine) in the Ad12-E1A13S and Ad12-E1A12S  proteins. BMK cells transformed by mutant Ad12-E1A (Ad12-E1Am) plus Ad12-E1B via retrovirus-mediated gene transfer showed features comparable to wild-type Ad12-E1A (Ad12-E1Awt) plus Ad12-E1B-transformed cells: they formed foci in soft agar and produced tumours in immunodeficient nude mice, although after a prolonged latency period. These results suggest that Ad12-E1A9.5S and Ad12-E1A11S/10S are dispensable for cellular transformation. However, in contrast to Ad12-E1Awt cells, Ad12-E1Am cells failed to grow to tumours in syngeneic, immunocompetent rodents, with the exception of one cell line, which produced tumours in about 50% of the immunocompetent animals. Interestingly, the concentration of the putative tumour suppressor and co-activator p300 was elevated in cell lines expressing high levels of Ad12-E1A and Ad12-E1B due to an increased half-life. These results indicate that p300 is stabilized in Ad12-E1-transformed BMK cells, probably by a mechanism linked to high expression of Ad12-E1A/E1B.