bluuebunny/crossref_metadata_2025 huggingface dataset:
Antisense Inhibition of Cyclooxygenase-2 Causes a Selective Suppression of the Na+-H+ Exchanger Isoform 3 in Rat Kidney in Experimental Colitis
Authors: Khan Islam
Published: April 2003

Background: Experimental colitis induces the expression of Na+-H+ exchanger (NHE) isoforms 1 and 3 in the rat colon, however, their status in rat kidney is not established. Objectives: The renal cortical NHE-1 and -3 expression was examined in the colitic rats. Since cyclooxygenase-2 (cox-2) plays an important role in inflammation, its regulatory role on these isoforms was also investigated by using a cox-2-selective phosphorothioated antisense oligonucleotide (S-oligo). Methods: Male Sprague-Dawley rats having colitis induced by acetic acid or trinitrobenzenesulfonic acid (TNBS) were given injection of S-oligo (3 mg/kg, i.p.) and a mismatched control oligonucleotide (C-oligo) daily 2 h before inducing colitis. Colonic myeloperoxidase activity (MPO) was used to indicate colitis. The renal cortical levels of NHE-1, NHE-3 and α-actin, an internal control, were estimated by the Western blot analysis. Results: Colonic MPO activity was increased and urine output was decreased in both models of colitis. Serum, but not the renal cortical level of TNF-α, was increased in both cases. Only TNBS condition showed an increased PGE2 level and a decreased body weight. Water intake and renal histology remained unchanged in either case. The NHE-3 protein, localized on the proximal tubules, was increased significantly without any change in NHE-1 and α-actin in both cases. These changes, except the body weight, were significantly reversed by the S-oligo. Conclusions: Selective induction of NHE-3 and TNF-α, and their reversal by cox-2 inhibition, suggest a cox-2-dependent regulation of NHE-3, which possibly involves TNF-α released from the site of inflammation and not from the kidney in colitis. The induction of NHE-3 is independent of the nature of colitides, and might be important to compensate for the loss of electrolyte and water in experimental colitis.
Evaluation of Valaciclovir Dosage Reduction in Continuous Ambulatory Peritoneal Dialysis Patients
Authors: Stathoulopoulou F. , Dhillon S. , Thodis H. , Stathakis C. , Vargemezis V.
Published: April 2003

In continuous ambulatory peritoneal dialysis (CAPD) patients, acyclovir-induced neurotoxicity is reported to be associated with high serum drug levels even when following the recommended reduced doses for this renal failure population. In view of the high oral bioavailability of valaciclovir (the L-valyl ester of acyclovir) the risk of neurotoxicity becomes more prominent. The present study was conducted in 12 CAPD patients who were administered a single oral dose of 500 mg valaciclovir. Acyclovir was analyzed by high-performance liquid chromatography. Relative pharmacokinetic parameters were estimated based on acyclovir concentrations at 8, 12 and 24 h post-dose. High inter-patient variations were observed with acyclovir apparent total clearance 7.238 ± 4 l/h and half-life (T1/2) 22.27 ± 16.82 h. However, dosage simulations confirmed supratherapeutic acyclovir concentrations for all participants when following the recommended dose of 1,000 mg valaciclovir/24 h for varicella zoster infections.
Remission Induction of Refractory Anaemia with Excess Blasts in Transformation by Sole Treatment with Granulocyte Colony-Stimulating Factor with Persistent Chromosomal Abnormality
Authors: Kondo Haruki , Kasahara Yasunori , Mori Akinori
Published: April 2003

We report a patient with myelodysplastic syndrome (MDS), refractory anaemia with excess blasts in transformation, in whom complete remission (CR) was achieved with the administration of granulocyte colony-stimulating factor (G-CSF). The 76-year-old patient was admitted to our hospital with a fever and a productive cough; a diagnosis of pneumonia was thus made. Following treatment with antibiotics, the patient’s condition improved, and MDS was diagnosed from peripheral blood and bone marrow examinations after the patient recovered from the infection. The patient achieved a sustained haematological CR that was confirmed by morphological and flow cytometric examination after treatment with G-CSF alone, although chromosomal abnormalities persisted. According to the literature, in almost all patients with acute myeloid leukaemia or MDS who were reported to achieve CR by G-CSF, the course was associated with infection, although our case did not have this complication during the course of G-CSF therapy. We suggest that patients with G-CSF alone without infection can achieve CR and that this may be related to a differentiation effect of G-CSF based on persistent chromosomal abnormality in this case.
Soy Milk with a High Glycitein Content Does Not Reduce Low-Density Lipoprotein Cholesterolemia in Type II Hypercholesterolemic Patients
Authors: Sirtori Cesare R. , Bosisio Raffaella , Pazzucconi Franco , Bondioli Alighiero , Gatti E. , Lovati Maria Rosa , Murphy Patricia
Published: April 2003

In order to evaluate acceptability and effectiveness of a partial addition of soy protein to the daily diet in well-established type II hypercholesterolemic individuals, a double-blind study was carried out with a soy milk providing 25 g/day of protein versus an identically formulated cow’s milk. Twenty patients with type II hypercholesterolemia, 4 males and 16 females, age range 38–76 years, all with cholesterol levels >7 mmol/l and low-density lipoprotein cholesterol <5.5 mmol/l, were selected. Significant triglyceride elevations (WHO Fredrickson type IIB) were present in 4 patients, and the body mass index was 24.2 ± 3.47 kg/m2. Different from prior studies, either with isoflavone-free products or with a moderately isoflavone-rich milk, the milk in the present study did not reduce total and low-density lipoprotein cholesterolemia. A detailed analysis of the composition showed significant differences in the isoflavone content versus products used in prior studies with a positive outcome. Soy milk isoflavones were, in fact, characterized by a high glycitein content and a low genistein/daidzein ratio. Glycitein is a minor component in most soy products, and its role in cholesterol regulation is unclear. In view of the high interest in the use of soy products for the prevention of coronary diseases, the metabolic behavior of different isoflavones in man should be better characterized, and the role of isoflavone composition of soy products given for the control of cholesterolemia needs further clarification.
Postmortem MRI and Histopathology of White Matter Changes in Alzheimer Brains
Authors: Bronge Lena , Bogdanovic Nenad , Wahlund Lars-Olof
Published: April 2003

To evaluate whether magnetic resonance imaging (MRI) of white matter changes in Alzheimer’s disease either under- or overestimates the findings on neuropathology. Postmortem MRI and neuropathological examination were performed on 6 brains from elderly individuals with a postmortem diagnosis of AD. Using a specially designed brain slicer, the brains were cut corresponding to the MRI images, and stained by Luxol Fast Blue. Quantitative analysis of white matter changes on MRI and neuropathology was performed using stereological principles. Measures from MRI and pathology were highly correlated (r2 = 0.71). However, pathology showed significantly more extensive changes than did MRI in all cases, with a mean of 54% larger areas. The lesions not identified with MRI represented, however, only minor changes with lower intensity of myelin staining and with an accentuation of the distance between fibres but with preserved axonal network and glial cell density.
Activation Thresholds of KV, BK andCl Ca Channels in Smooth Muscle Cells in Pial Precapillary Arterioles
Authors: Cheong A. , Quinn K. , Dedman A.M. , Beech D.J.
Published: April 2003

We have previously shown expression of voltage-gated K+ channels (KV) in smooth muscle of cerebral arterioles and suggested the channels function to oppose voltage-dependent Ca2+ entry. However, other studies indicate that large conductance Ca2+-activated K+ (BK) channels serve this function and chloride (Cl–) channels may have the opposite effect. In this study we compared the activation thresholds and absolute current amplitudes for KV channels, BK channels and Cl– channels at physiological membrane potentials in intact precapillary arterioles from the rabbit cerebral circulation. Patch-clamp recordings were made to measure current and membrane potential, and a video scan line was used to detect external diameter. Two strategies to determine the basal current-voltage relationship of BKchannels showed the channels contributed current only at voltages positive of –35 mV, even though voltage-dependent Ca2+-entry occurred. Ca2+-activated and niflumic acid-sensitive Cl– current was detected but, between –50 and –10 mV, both BK and Cl– channel currents were much smaller and contributed less to the membrane potential compared with KV channel current. Furthermore, in the absence of an exogenous vasoconstrictor agent, block of KV channels but not BK or Cl– channels caused constriction, although in the presence of endothelin-1 block of BK or KV channels caused constriction. The data indicate KV channels are the first inhibitory mechanism to activate when there is depolarisation in precapillary arteriolar smooth muscle cells of the cerebral circulation.
Microtubule-Dependent Regulation of Vasomotor Tone Requires Rho-Kinase
Authors: Platts Steven H. , Martinez-Lemus Luis A. , Meininger Gerald A.
Published: April 2003

Changes in microtubule polymerization state have been shown to affect many cellular events, including the contractile properties of smooth muscle. We have previously shown that depolymerization of microtubules causes significant vasoconstriction in arterioles. This vasoconstriction does not require the endothelium or an increase in vascular smooth muscle Ca2+. Consequently, we hypothesized that a Ca2+-sensitizing mechanism may be involved in the constrictor response. The purpose of these experiments was to further elucidate cell signaling pathways responsible for vasoconstriction following microtubule disruption. Rat skeletal muscle arterioles were isolated, cannulated and pressurized without intraluminal flow. All arterioles used for experiments developed spontaneous, myogenic tone (54% of passive diameter). Microtubule depolymerization with colcemid or vinblastine caused arterioles to constrict by an additional 20% from resting basal diameter. In addition, arterioles treated with colcemid showed significantly enhanced responsiveness to norepinephrine and reduced responsiveness to adenosine. To investigate a role for Rho-kinase, vessels were incubated with inhibitors of the Rho-kinase pathway – Y-27632 or C3 exoenzyme. Inhibition of Rho-kinase significantly inhibited the constriction associated with colcemid-induced microtubule depolymerization. Inhibition of Rho-kinase also abolished the increased responsiveness to norepinephrine whereas adenosine responsiveness continued to be reduced. By comparison, inhibition of the tyrosine kinase, Src, with PP2 did not have any effect on the colcemid-induced changes in vascular tone or reactivity. These data indicate that the vasoconstriction and enhanced norepinephrine reactivity associated with microtubule disruption involves a Ca2+-sensitization process that is mediated by the Rho-kinase pathway.
Bone Resorption in Chronic Otitis media: The Role of the Osteoclast
Authors: Jung Jae Y. , Chole Richard A.
Published: April 2003

Most of the pathology associated with cholesteatoma is the result of osteoclast-mediated bone resorption in the middle ear. Cytokines, prostaglandins, nitric oxide, neurotransmitters and growth factors are associated with chronic inflammation and have been implicated in cholesteatoma-induced bone resorption. Although many different factors are known to regulate osteoclast activation, there is a final common pathway of osteoclast differentiation and resorption. Recent advances in molecular techniques and the increasing availability of genetically altered mice have provided valuable insight into the molecular mechanism of osteoclastic bone resorption. This review focuses on osteoclast biology, lessons from genetically altered mice, and their contribution to our understanding of cholesteatoma-induced bone resorption.
Feasibility of Source Images of Computed Tomographic Angiography to Detect the Extent of Ischemia in Hyperacute Stroke
Authors: Grond M. , Rudolf J. , Schneweis S. , Terstegge K. , Sobesky J. , Kracht L. , Neveling M. , Heiss W.-D.
Published: April 2003

Background and Purpose: Computed tomographic angiography (CTA) is suggested to be a promising tool for patient selection for thrombolytic therapy of acute stroke. It does not only provide information on intracranial vasculature, but also on the capacity of the collateral circulation and the pattern of poorly perfused brain tissue. The objective of our study was to evaluate whether the presence and size of critically hypoperfused tissue assessed with flow positron emission tomography (PET) as a gold standard can reliably be identified on CTA source images. Methods: Fifteen potential candidates for early thrombolysis underwent CTA 65–170 min (mean 107 min) after the onset of acute anterior circulation stroke. Regional cerebral perfusion was measured between 27 and 86 min (mean 59 min) later with [15O]-H2O and PET, and the volume of critically hypoperfused cortical tissue was assessed. CTA source images were evaluated by a neuroradiologist and an experienced stroke neurologist. The patients were classified into three groups according to the presumed size of the perfusion deficit on CTA (large, small, no perfusion deficit). Results: PET revealed the presence of critical cortical hypoperfusion in 10 patients, 5 had no critical cortical hypoperfusion. The neuroradiologist correctly identified the presence of a perfusion deficit in all patients, the neurologist had two false negative and one false positive ratings. Concerning the size of the perfusion deficit, there was considerable inaccuracy in both raters. Conclusions: The usefulness of CTA source images in yielding information about the perfusion state of stroke patients in clinical routine should not be overestimated.
Comparison of Short (3-Day) Hospitalization followed by Home Care Treatment and Conventional (10-Day) Hospitalization for Acute Ischemic Stroke
Authors: Suwanwela Nijasri C. , Phanthumchinda Kammant , Limtongkul Sakchai , Suvanprakorn Pichit
Published: April 2003

This prospective randomized controlled study was designed to compare the treatment efficacy, safety and quality of life of ischemic stroke patients treated with conventional (10-day) hospitalization or short (3-day) hospitalization followed by home care treatment. One hundred and two patients with acute ischemic stroke who arrived within 48 h after symptom onset and met the inclusion criteria were studied. Patients were randomly assigned to either of two groups of treatment. Patients in the ‘hospitalization’ group were hospitalized for 10 days, whereas those in the ‘home care’ group were admitted only for the first 3 days and were followed at home under the home care program. The baseline characteristics were similar in the two groups. There was no difference in the number of deaths or dependency defined by the Modified Rankin scale more than or equal to 3 between the two groups at 6 months. The relative risk was 0.85 with a 95% confidence interval between 0.35 and 2.04. There was also no difference in the number of patients who had good outcome (NIHSS between 0 and 2 and Barthel index between 75 and 100) at 6 months. One patient in the home care group died due to massive intracerebral hemorrhage. Seventy-nine percent of patients in the home care group were satisfied with the home treatment program.
Long-Term Prognosis of Cerebral Vein and Dural Sinus Thrombosis
Authors: Ferro J.M. , Lopes M.G. , Rosas M.J. , Ferro M.A. , Fontes J.
Published: April 2003

The purpose of this study was to analyze the long-term mortality, functional recovery and long-term complications of cerebral vein and dural sinus thrombosis (CVDST) admitted to Portuguese hospitals. A follow-up of symptomatic CVDST admitted to Portuguese hospitals since 1980 was performed. Fifty-one patients (retrospective cases) were re-evaluated during 1996; 91 consecutively admitted patients from 6/1995 to 6/1998 were followed up to 1999. In 1996, 4 (8%) of the retrospective cases had died (3 patients died in the acute phase), 4 (8%) could not be reached, 33 (64%) had recovered completely (Rankin 0 or 1) and 3 (6%) were dependent. The prospective cases had a mean follow-up of 1 year: 6 (7%) patients died in the acute phase, one (1%) died during follow-up, 75 (82%) recovered completely, and only 1 (1%) was dependent. For the prospective cases, worsening after admission (OR = 18.2; 95% CI = 2.9–112.4) and encephalopathy as the presenting syndrome (OR = 7.1; 95% CI = 1.2–40.9) predicted death or dependency, while absence of aphasia (OR 6.7, 95% CI = 1.6–33) and no worsening after admission (OR = 5.9; 95% CI = 1.6–20) predicted total recovery. During follow-up of the prospective cases, 4 (5%) patients had thrombotic events, 8 (10%) patients experienced seizures, 9 (11%) complained of severe headaches and 1 patient suffered severe visual loss. The long-term functional prognosis of patients with CVDST was fairly good with complete recovery in the majority of cases. However, these patients had a moderate risk of further thrombotic events and seizures.
Lactoperoxidase Inhibits Glucosyltransferases from Streptococcus mutans in vitro
Authors: Korpela A. , Yu X. , Loimaranta V. , Lenander-Lumikari M. , Vacca-Smith A. , Wunder D. , Bowen W.H. , Tenovuo J.
Published: April 2003

This study examines the possible effect of the antimicrobial peroxidase system on the activity of streptococcal glucosyltransferases B, C and D (GtfB, GtfC and GtfD), either in solution (GtfB and GtfC) or when adsorbed to hydroxyapatite (GtfC and GtfD) at pH 6.5. The lactoperoxidase (LP) system (LP, H2O2, SCN–) had no effect on the activity of dissolved GtfC, but the activity of dissolved GtfB was enhanced. The LP system, however, strongly inhibited the activities of both GtfC and GtfD in their adsorbed form. LP enzyme, without its substrates, inhibited all three Gtf enzymes: GtfB and GtfC in concentrations between 10 and 100 µg/ml in liquid phase and adsorbed GtfC and GtfD in concentrations between 25 and 50 µg/ml. This inhibition was in part abolished in liquid phase, but not in solid phase, if the substrates of LP were added. This study shows that the lactoperoxidase system can exert inhibitory activity against streptococcal Gtfs without generating oxidizing agents.
Microcystic Adnexal Carcinoma: Review of 51 Japanese Patients
Authors: Ohtsuka Hisashi , Nagamatsu Shogo
Published: April 2003

Background: Microcystic adnexal carcinoma (MAC) has been reported to occur predominantly in Caucasians. However, the number of cases in Japanese subjects seems to have recently been increasing. Objective: To review the Japanese cases of MAC. Methods: We collected and analyzed the data of 51 Japanese patients recorded in case reports or abstracts over a number of years. Results: Twenty-five of the cases were reported between 1987 and 1996, and the remaining 26 cases between 1997 and 2000. Forty-three lesions were located on the face, 2 on the scalp, 2 on the chest, 1 on the axilla, 1 on the buttock, 1 on the palm and 1 on the toe. One of the above occurred at the site of previous radiotherapy. Fifteen tumors were initially misdiagnosed histopathologically. Conclusion: Our review shows that MAC also occurs in the Japanese, in whom it may be more common than previously observed.
Longitudinal Changes in Brain CT Scans and Development of Dementia in Down’s Syndrome
Authors: Ikeda Masayuki , Arai Yukio
Published: April 2003

To determine the relationship of the development of dementia to longitudinal changes in brain CT scans in patients with Down’s syndrome (DS), we studied 14 Japanese DS patients at an interval of 10 years. The age at entry to the study was 35.7 ± 9.9 (mean ± SD) years in 1989 when we did the first CT scans. We performed the second CT scans in 1999 and quantitatively compared them with those taken in 1989. The 4 oldest of the patients (the demented group, 55.3 ± 1.4 years of age in 1999) developed symptoms of cognitive decline before 1999. The younger 10 (the non-demented group, 41.9 ± 9.0 years of age in 1999) remained stable in cognitive function until 1999. Despite the clear difference between the demented and the non-demented group in brain atrophy in 1999, CT measures of the demented group were similar to those of the non-demented group in 1989. These results indicate that age is a better predictor of dementia than imaging studies and that CT does not show a quantitative difference between the demented and the non-demented group before the onset of dementia.
F175S Change and a Novel Polymorphism in Presenilin-1 Gene in Late-Onset Familial Alzheimer’s Disease
Authors: Colacicco A.M. , Panza F. , Basile A.M. , Solfrizzi V. , Capurso C. , D’Introno A. , Torres F. , Capurso S. , Cozza S. , Flora R. , Capurso A.
Published: April 2003

We analyzed at the molecular level with presenilin-1 (PS-1) and apolipoprotein E (apoE) genotyping the affected subjects and asymptomatic relatives of an Italian family with several members affected by late-onset familial Alzheimer’s disease (AD). The screen for PS-1 gene mutations revealed a novel missense substitution phenylalanine 175 to serine in 1 of the affected individuals and 2 asymptomatic sons of the patient. This change was not found in other relatives of this family, as well as in 60 individuals with sporadic late-onset AD and 40 normal controls. Furthermore, a GG/TT substitution in the 3′ end of intron 6 at the boundary with exon 7 was found in all relatives of the second and third generations of this family. All the affected relatives were female homo- or heterozygotes for apoE Ε4 allele. This study provides evidence that a PS-1 gene missense change does not necessarily associate with early-onset disease, and can occur in single cases affected by late-onset disease.
Low-Dose Botulinum Toxin-A Treatment of Cervical Dystonia – A Double-Blind, Randomized Pilot Study
Authors: Laubis-Herrmann Ulrike , Fries Katja , Topka Helge
Published: April 2003

The purpose of the study was to evaluate the clinical efficacy of low-dose botulinum toxin (BTX) treatment of cervical dystonia in a double-blind, randomized pilot study. Thirty-one patients with cervical dystonia and a minimum of 2 previous Dysport® treatments received either a mean total target dose of 547 ± 113 mouse units (MU) (group A, 500 MU Dysport/ml) or a 4-times-diluted preparation 130 ± 32 MU (group B, 125 MU Dysport/ml). Assessment was made before and 4 weeks after the injection using Toronto Western Spasmodic Torticollis Rating Scales (TWSTRS). Additionally, a self-response scale evaluated the patients’ subjective condition for 12 weeks after injection. TWST rating before and after injection revealed comparable clinical improvement in both groups. The severity of cervical dystonia at study entry had no effects on therapeutic effects of either preparation. Self-rating revealed comparable subjective improvement in both groups; however, 3 patients of group B received reinjections due to insufficient effects of the injection. Our findings suggest that low-dose treatment of cervical dystonia with Dysport may be clinically effective during maintenance therapy, at least for a limited period of time. Long-lasting effects of previous Dysport treatments at conventional doses and possibly improved diffusion of a highly diluted toxin preparation may have contributed to the effects of the low-dose regimen. Our data emphasize the need for further studies in order to clearly identify optimal toxin preparations for therapeutic uses of BTX-A in neurologic disorders.
Speech-Language Pathology in the Philippines: Reflections on the Past and Present, Perspectives for the Future
Authors: Cheng Winston T. , Olea Tricia Christina M. , Marzan Jocelyn Christina B.
Published: April 2003

The field of speech-language pathology in the Philippines has come a long way since its inception in 1978. This article provides an overview of the profession, including a description of the distribution, work settings, and scope of practice of the speech-language pathologists in the Philippines. It highlights the strengths and unique aspects of the profession such as the experience of working with bi-/multilingual clients, honed clinical reasoning, family involvement, and exposure to inter- and transdisciplinary approaches to service delivery. Further, this paper discusses issues and challenges that need to be addressed for continued growth of the profession.
Education of Speech and Language Therapists in the Republic of Ireland and in the UK
Authors: Leahy M.M. , Supple M.M.
Published: April 2003

A brief history of speech and language therapy education in the Republic of Ireland and in the UK is provided, with reference to early 20th century developments. Current practice regarding the regulation and accreditation processes of education courses in the two countries is outlined. A general account of the development of undergraduate curricula of speech and language therapy is provided.
Die Wunschsectio – Eine gleichwertige Alternative zur Spontangeburt?
Authors: Schneider Henning
Published: April 2003

Die Fortschritte bei der perioperativen Behandlung, im Bereich der Anästhesie und bei der Verfeinerung der Operationstechnik haben den Kaiserschnitt zu einem für Mutter und Kind sehr sicheren Eingriff werden lassen. Durch die rechtzeitige Entbindung durch eine Sectio kann in bestimmten Risikosituationen die Mortalität und Morbidität vor allem des Kindes deutlich gesenkt werden. Der Schluss, dass unter heutigen Gegebenheiten der primäre Kaiserschnitt eine gleichwertige Alternative zur natürlichen Geburt ist, so dass neben der medizinischen Indikation vor allem auch der Wunsch der Schwangeren für den Entscheid über den Geburtsmodus ausschlaggebend sein sollte, ist allerdings nicht gerechtfertigt. Die kritische Analyse der Daten von umfangreichen regionalen Perinatalerhebungen zeigt, dass das Risiko für leichte sowie auch schwere Komplikationen bei der Mutter nach einem primären Kaiserschnitt deutlich höher als nach einer Spontangeburt ist. Auch mit einer erhöhten kindlichen Morbidität in Form von mehr oder weniger schweren respiratorischen Problemen ist zu rechnen. Besonders gravierend ist das erhöhte Risiko für Mutter und Kind für negative Auswirkungen bei Folgeschwangerschaften, wie eine Uterusruptur oder aber Störungen der Plazentation im Narbenbereich. Ob diese zum Teil schwerwiegenden Zusatzrisiken durch ein höheres Risiko für Beckenbodenverletzungen mit Funktionsstörungen der Blase und des Rektums nach vaginaler Entbindung oder die sehr seltenen Fälle von schwerer kindlicher Asphyxie, die durch einen geplanten Kaiserschnitt verhindert werden können, aufgewogen werden, erscheint zumindest fragwürdig. In jedem Fall bedarf es einer sehr sorgfältigen Aufklärung der Frau über diese Risiken, und die medizinische Indikation muss gegenüber dem Wunsch der Frau den Vorrang behalten.
Early Puberty in Adopted Children
Authors: Mul D. , Oostdijk W. , Drop S.L.S.
Published: April 2003

Early puberty is frequently observed in adopted children. In various studies, early puberty has been associated with decreased final height. In Europe, studies were undertaken to treat early puberty in adopted children with GnRH agonist. This article reviews the current understanding of early puberty in adopted children, including prevalence, background and treatment options. Data from the European studies are briefly described. Besides auxological aspects, psychological items are addressed as well. Studies on the psychological effect of early puberty in adopted children are reported. Future issues include further study in the mechanism of early puberty in adopted children, evaluation of final height results of the growth studies and quality of life assessments in this specific group of children.
Light Symptoms following a High-Dose Intentional L-Thyroxine Ingestion Treated with Cholestyramine
Authors: de Luis D.A. , Dueñas A. , Martin J. , Abad L. , Cuellar L. , Aller R.
Published: April 2003

Adult exposure to L-thyroxine has a wide range of presentations: most adults either do not develop symptoms or only become minimally symptomatic. Appropriate treatments after exposure to L-thyroxine have yet to be established. A 26-year-old woman with a suicidal intention was witnessed to ingest approximately 50 L-thyroxine tablets, each containing 0.1 mg L-thyroxine (total dose 5 mg). Cholestyramine was administered (4 g every 8 h p.o.). Vital signs were monitored every 6 h and the hormone levels (L-thyroxine and thyroid-stimulating hormone) every 24 h. The thyroxine levels increased, and the thyroid-stimulating hormone levels decreased, with a normalization of the L-thyroxine level on postingestion day 6. Hypertension, dysrhythmias, and delusions did not appear in our patient. Only distal tremor and diaphoresis appeared on day 1 after ingestion. Cholestyramine has been used in cases of iatrogenic hyperthyroidism, in patients with Graves’ disease, and in patients with digoxin intoxications, with good responses in all cases and a low incidence of side effects. This case illustrates the potential utility of cholestyramine to treat L-thyroxine intoxications.
A Rapid, Quantitative Immunofunctional Assay for Measuring Human Leptin
Authors: Kratzsch Jürgen , Berthold Antje , Lammert Alexander , Reuter Wolfgang , Keller Eberhard , Kiess Wieland
Published: April 2003

Background: We have developed a rapid, sensitive and quantitative in vitro assay for leptin based upon its ability to bind to the soluble extracellular domain of the leptin receptor (sOB-R). Such an assay is theoretically capable of differentiating between physiologically active leptin molecules from those with modified, either enhanced or reduced, binding activity. Methods: A preparation of sOB-R was immobilized to capture leptin from serum samples or standards. Anti-leptin antibodies that had been raised in rabbits were added in a second incubation step to identify leptin molecules bound to sOB-R. Signal detection was performed in a third incubation step by anti-rabbit IgG labeled with peroxidase. The immunofunctional assay (IFA) was clinically validated by the comparison of leptin levels in adolescents (n = 41, age range 9–18 years, BMI range 13.4–33.8 kg/m2) and adults (n = 80, age range 18–77 years, BMI range 16.4–54.7 kg/m2) measured using the IFA with data of an in-house RIA performed with the same standards and leptin antibodies. Results: The functional sensitivity of the IFA was 0.4 ng/ml and comparable to the data of the RIA. Intra- and interassay coefficients of variation were below 12.5 % in both methods. Leptin levels correlated well with the BMI of the subjects studied (r = 0.70 for RIA, r = 0.72 for IFA; p < 0.0001) as well as between IFA (y) and RIA (x) (y = x –1.31 ng/ml; r = 0.97, p < 0.0001). The median of the quotient between IFA and RIA levels was 0.86 (quartile range 0.60–1.10) for all samples.Conclusions: So far, only at the most minor differences between leptin measurements using the newly developed IFA and those using a conventional RIA have been detected. Additional studies using the IFA method are required to investigate whether or not discrepant results with the IFA will be seen in various states of relative leptin resistance and whether or not such differences are of biological relevance.
17-Hydroxylase/17,20 Lyase Deficiency Diagnosed during Childhood
Authors: Wolthers O.D. , Rumsby G. , Techatraisak K. , Honour J.W. , Hindmarsh P.C.
Published: April 2003

We present a case of familial 17α-hydroxylase/17,20 lyase (CYP17) deficiency in which the index case, a 14-year-old XX girl, led to the diagnosis of the condition in a 9-year-old XY sister. No mutations in the CYP 17 gene were found in any of the girls.
Recognition of Resveratrol by the Human Estrogen Receptor-Alpha: A Molecular Modeling Approach to Understand Its Biological Actions
Authors: El-Mowafy Abdalla M. , Abou-Zeid Laila A. , Edafiogho Ivan
Published: April 2003

Objectives: Resveratrol (RSVL) is an edible phytoestrogen with multifaceted health benefits that may originate from binding to the estrogen receptors. Despite its structural similarity to the estrogen receptor-α (ERα) agonist diethylstilbestrol (DES), RSVL showed distinct biological profiles in estrogen-responsive biological systems. The molecular basis of such biological profiles has been undefined. Methods: We considered possible orientations for RSVL in ERα binding pocket. These conformations have been analyzed based on: (i) alignment with the key pharmacophoric elements of DES; (ii) computational energy of interaction, and (iii) pattern of accommodation at the ERα binding pocket. The characteristics of the most favored RSVL orientation have been compared with those of DES. Results: Both RSVL and DES interacted with the catalytic amino acid triad of the ERα pocket (His524, Arg394 and Glu 353). However, unlike the Erα agonists DES and estradiol (E2), RSVL formed three additional hydrogen bonds with Gly521 and Leu525, two paramount ligand recognition residues, and with Met343 at the ERα binding cavity. Lastly, RSVL displayed a more favorable energy of interaction with the ERα binding cavity. Conclusions: The present study suggests, for the first time, that RSVL is well recognized by the human ERα but in a manner distinct from the pure agonists DES and E2. These variations may well entail the unique biological responses of RSVL in ER-responsive systems.
Inhibition of Platelet Aggregation by Rat Trophoblasts
Authors: Tewari R. , Singh M.P. , Farheen S. , Dikshit M. , Mehrotra P.K.
Published: April 2003

Objective: To determine the effect of rat trophoblast cell suspensions on adenosine diphosphate (ADP)-induced platelet aggregation. Materials and Methods: The trophoblasts were isolated from ectoplacental cones (a pre-placental tissue very rich in trophoblasts) developed in rat embryos on day 12 of pregnancy (normal period of gestation: 22–23 days). Platelet-rich plasma (PRP) was obtained from adult male rats. The trophoblasts were preincubated (37°C, 30 min), suspended in the medium, and then re-incubated with PRP for 3–5 min. Results: 5 × 104 and 7 × 104 trophoblasts inhibited ADP-induced platelet aggregation by 10 and 18%, respectively. When the trophoblast cell concentration was increased to 1– 2 × 105 cells, a proaggregatory phenomenon was observed, even in the absence of ADP. However, there was no inhibition of aggregation or promotion of aggregation when fixed trophoblasts or live endometrial stromal cells were incubated with PRP. Conclusion: The results indicate that the aggregation inhibition response was cell specific and concentration dependent. A 68-kD protein was detected in the medium when it was conditioned with 5–7 × 104 but not with 1–2 × 105 trophoblasts. However, the inhibitory or stimulatory effect does not seem to be dependent on the presence of this protein.
Diagnostic Dilemmas in Acute Intermittent Porphyria
Authors: Periasamy Vembu , Al Shubaili Asmahan , Girsh Y.
Published: April 2003

Objective: To present the importance of early diagnosis of acute intermittent porphyria (AIP) in patients with atypical presentation and discuss the diagnostic problems encountered in this case. Clinical Presentation: A 15-year-old girl presented with upper respiratory tract infection, fever, seizures and abdominal pain. An initial diagnosis of encephalitis was made. She received antiviral drugs and anticonvulsants. Two weeks later, she developed progressive flaccid quadriplegia and facial weakness. She also developed respiratory paralysis and was intubated. Cytoalbuminous dissociation was seen in the cerebrospinal fluid. A diagnosis of severe Guillain-Barré syndrome was made. Intervention: The patient received a course of intravenous immunoglobulins which did not result in any clinical improvement. Plasmapheresis, started after 12 weeks, led to partial improvement. The patient continued to have attacks of seizures, abdominal pain and vomitting with severe quadriparesis. A repeat screening test for urine porphyrins was positive, and AIP was confirmed by specific porphobilinogen deaminase in the blood. The patient was treated with large doses of intravenous glucose, followed by injections of hematin. The patient improved remarkably. She was extubated, discharged from Intensive Care Unit and started on a rehabilitation program. Conclusion: This patient was initially diagnosed erroneously with a negative screening test for AIP and consequently treated inappropriately. The proper diagnosis was made after repeating the screening test followed by specific tests of porphobilinogen deaminase.
Clinical Data on Restless Legs Syndrome: A Dose-Finding Study with Cabergoline
Authors: Stiasny Karin
Published: April 2003

Current treatment options for restless legs syndrome (RLS), based on the American Academy of Sleep Medicine practice parameters, favor dopaminergic agents. The drug of first choice is levodopa, which is now licensed for RLS in two European countries. However, the short duration of action and augmentation of symptoms under therapy may limit the clinical use of levodopa, especially in severely affected patients. An open pilot study shows that the long-acting dopamine agonist cabergoline is a promising new tool in the treatment of RLS. Results of a double-blind, controlled trial are pending.
Growth Prediction Models, Concept and Use
Authors: Kriström Berit , Albertsson Wikland Kerstin
Published: April 2003

There is a principal and qualitative difference between using regression results on data from groups of children, and using validated prediction models for individual children. Using accurate models, it is now possible to predict the growth response to growth hormone (GH) treatment in a slowly growing child with GH deficiency (GHD) or in a child with idiopathic short stature (ISS). The growth response to the standard dose of GH can be regarded as a bioassay for GH (i.e. the tissue GH responsiveness) and the information on this growth response can be used for different purposes: to decide about treatment or not, for monitoring, and for adjusting the GH dose in order to reach a defined goal for height. This last concept is now used in an ongoing prospective randomized GH dose-finding trial.
IMAGe Association: Additional Clinical Features and Evidence for Recessive Autosomal Inheritance
Authors: Lienhardt Anne , Mas Jean-Christophe , Kalifa Gabriel , Chaussain Jean-Louis , Tauber Maïthé
Published: April 2003

Congenital adrenal hypoplasia (CAH) normally occurs in the neonatal period, with patients presenting with more or less severe salt-wasting syndrome. X-linked CAH has been associated with mutations in the DAX-1 gene, and boys have also been shown to have hypogonadotrophic hypogonadism. Recently, in three unrelated boys, CAH was associated with intrauterine growth retardation (IUGR), metaphyseal dysplasia and genital abnormalities, defining a new association called IMAGe. We now report four additional patients with this association, including the first living female. The four patients belong to two unrelated families (one brother and one sister from each family). These patients have the main clinical characteristics of IMAGe association: IUGR, facial dysmorphy (frontal bossing, broad nasal bridge, low-set ears), short limbs due to metaphyseal dysplasia, and adrenal insufficiency. As these patients are older than the initial three patients, we can also describe additional features: short adult height, normal puberty in boys as well as in the living girl. The boys have hypospadias associated with micropenis. The living girl came to clinical attention at the age of 5 years as a result of a familial survey, and careful questioning revealed that she had been suffering from mild adrenal insufficiency since early childhood. At least one boy has congenital hypotonia due to muscular dystrophy. In conclusion, these four new cases display familial transmission, strongly suggesting Mendelian autosomal recessive inheritance. Adrenal insufficiency may be mild. Hypotonia, described in all the patients, might be related to paucisymptomatic muscular dystrophy, as this condition is clearly heterogeneous varying with regard to severity, associated manifestations and outcome. If this symptom is part of the syndrome, which we cannot assume, it could help to localize the candidate gene.
Posterior Cortical Atrophy: Clinical Characteristics and Differences Compared to Alzheimer’s Disease
Authors: Mendez Mario F. , Ghajarania Mehdi , Perryman Kent M.
Published: April 2003

Background: Predominant and progressive complex visual disorders are often due to posterior cortical atrophy (PCA), a rare early-onset dementing syndrome presenting with visual complaints. In clinicopathological studies, PCA is most commonly considered a form of Alzheimer’s disease (AD); no prior study has evaluated clinical differences between PCA and AD. Methods: This study identified 15 patients who presented with progressive complex visual disorders and predominant occipitoparietal hypoperfusion on SPECT. These patients were retrospectively compared on clinical variables with 30 patients with clinically probable AD matched for gender, age and duration of illness. Results: The PCA patients presented with alexia, elements of Balint’s syndrome, apperceptive visual agnosia, dressing apraxia and environmental disorientation along with elements of Gerstmann’s syndrome. Compared to the AD patients, the 15 PCA patients (mean age of onset 58 years, range 51–64) had significantly better verbal fluency, less memory difficulty, more depression and greater insight into their illness but similar familial and apolipoprotein E risk factors. In the PCA patients, MRI often showed occipitoparietal atrophy without detectable mesiotemporal atrophy. Conclusions: PCA is a distinct clinical syndrome and not just AD with prominent visual deficits. Compared to AD controls, PCA patients have better language and memory but more insight and depression and more posterior atrophy on MRI. These results indicate clinical criteria for the diagnosis of PCA and recommend specific interventions such as visual aids and antidepressant medications. Similar risk factors and course suggest that PCA is most commonly an early-onset posteriorly shifted AD variant.
Historadioautographic Localization of Oxytocin and V1a Vasopressin Binding Sites in the Kidney of Developing and Adult Rabbit, Mouse and Merione and of Adult Human
Authors: Arpin-Bott M.P. , Kaissling B. , Waltisperger E. , Rabhi M. , Saussine P. , Freund-Mercier M.J. , Stoeckel M.E.
Published: April 2003

The localization of oxytocin (OT) binding sites and vasopressin (VP) binding sites of the V1a subtype was investigated by radioautography in kidneys of rabbits, mice and meriones during postnatal development and in the adult, and in the human kidney. Kidney sections were incubated in the presence of selective radioiodinated OT and V1a antagonists, respectively. The localizations were compared with those previously described in the rat. The main finding of the study was the almost constant presence in the cortex of V1a binding sites in the connecting tubule, the cortical collecting duct and in the juxtaglomerular apparatus (on the intra- and extraglomerular mesangium and the afferent arteriole). This distribution suggests an interaction of VP via V1a receptors and the kallikrein-kinin system in the kidney. OT binding sites, in comparison with V1a binding sites, were fewer and less constantly detectable in the kidney of the different species. In the mouse, their presence on the limbs of Henle’s loop in the medulla points to the possibility of their involvement in the medullary concentrating process. In the kidneys of the various species, OT and V1a binding sites occurred always in differential structures. In contrast, in the human kidney cortex, a colocalization of OT and V1a binding sites was almost constantly observed. This raises the question as to the specificity of the neurohypophysial hormone receptors in the human kidney.
Foot Dimensions of Elderly People with and without Diabetes mellitus – a Data Basis for Shoe Design
Authors: Chantelau E. , Gede A.
Published: April 2003

Background: Injuries from footwear are common in elderly people, particularly in those with diabetes mellitus and polyneuropathy. A common cause is a mismatch between foot and shoe. Objective: To assess the length and the breadth of the feet by an automatic measuring device in 568 patients with diabetic polyneuropathy and in 100 nondiabetic control subjects of the same mean age of 64 years. Results: While the foot length in all cases matched well with the size of the normal footwear available on the market, more than two thirds of the feet were considerably broader than the normal footwear available. The foot breadth correlated variably with the foot length. Tables of foot dimensions for men and women are provided over the complete range of shoe sizes. Conclusions: This anthropometric data set on feet, which is the first conducted in elderly people, proves that most feet of elderly people with or without diabetic neuropathy do not fit ordinary casual footwear. Therefore, the construction of shoes according to the anthropometric data of elderly people is required in order to prevent foot injuries in this particular population.
Dehydroepiandrosterone Sulfate and Growth Axis Hormones in Patients with Ischemic Heart Disease
Authors: Osorio A. , Gutierrez M.A. , Ortega E. , Ruiz-Requena E.
Published: April 2003

Background: The present study aimed to determine whether decreases in dehydroepiandrosterone sulfate (DHEA-S) and growth axis components precede cardiovascular disease or are a consequence of it. Methods: We measured the concentrations in serum of DHEA-S, ACTH, cortisol, growth hormone, insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 in 30 male controls and also in 37 male patients on days 0, 2, 5, 7 and 9 after suffering a myocardial infarction (MI). Results: There was no significant variation in any of these parameters between the controls and the patients on day 0. However, we found a significant (p < 0.001) reduction in the DHEA-S concentrations of the patients between day 0 and subsequent days (days 2, 5, 7and 9). Conclusion: We conclude that the decrease in DHEA-S in patients with MI is a consequence and not a cause of the disease.
Serum Levels of Soluble CD26 and CD30 in Patients on Hemodialysis
Authors: Nakao Kazushi , Nagake Yoshio , Okamoto Akira , Ichikawa Haruo , Yamamura Masahiro , Makino Hirofumi
Published: April 2003

Background/Aims: Various abnormalities of the immune system have been demonstrated in patients on hemodialysis (HD). We hypothesize that the imbalance between type 1 helper T (Th1) cells and type 2 helper T (Th2) cells in patients on HD contributes to these abnormalities. Furthermore, we investigate the relationship between the Th1/Th2 imbalance and HD duration. Methods: We measured the serum levels of soluble CD26 (sCD26) and soluble CD30 (sCD30) in 47 patients on HD and in 13 patients with chronic renal failure not on HD and analyzed the effect of HD duration on the serum levels of sCD26 and sCD30. Results: The serum level of sCD26 in the HD group was significantly lower than that in the control group. On the other hand, the serum levels of sCD30 in the HD group and in the CRF group were significantly higher than in the control group. In the short-term HD group (<1 year), the serum levels of sCD26 were lower and the sCD30 levels higher than those in middle-term HD group (1–10 years). Conclusions: In the HD group, the Th1/Th2 balance may shift towards Th2 dominance. It is possible that this imbalance contributes to the abnormality of the immune system in HD patients.