bluuebunny/crossref_metadata_2025 huggingface dataset:
Isoproterenol Increases Renal Tubular Reabsorption of Phosphate in X-Linked Hypophosphatemic (Hyp) Mice
Authors: Thornton Lisa R. , Meyer Martha H. , Meyer Jr Ralph A.
Published: April 2003

Hypophosphatemic (Hyp) mice have a reduced renal retention of phosphate. The β-adrenergic agonist isoproterenol reverses phosphaturia induced by parathyroid hormone in the rat. This study determined whether isoproterenol could raise the renal tubular maximum transport of phosphate (TmP) in Hyp mice. Male 10- to 12-week-old normal and Hyp mice were infused with 3H-inulin and isoproterenol (0.0, 0.25, 0.5 and 1.0 µg/kg/min) in 0.9% NaCl. Glomerular filtration rate, plasma phosphate, urinary phosphate excretion, TmP, urinary sodium excretion, and urinary cyclic adenosine monophosphate were measured. As expected, Hypcontrols (0.0 dose) had a TmP which was significantly below that of normal controls: 1.15±(SEM) 0.6 (n = 9) versus 2.13±0.10 (n = 11) µmol P/ml glomerular filtrate (p<0.001). Isoproterenol at doses of 0.5 and 1.0 µg/kg/min elevated the TmP of Hyp mice to the level of normal controls: 1.94±0.19 (n = 7) and 1.98±0.10 (n = 9) µmol P/ml glomerular filtrate, respectively. These results indicate that the low tubular reabsorption of phosphate in Hyp mice is not due to a fixed low level of phosphate transport, but to decreased stimulation of phosphate transporters, since Hyp mouse kidneys increase phosphate reabsorption with suitable stimulus.
Glucocorticoids and Acidification Independently Increase Transcription of Branched-Chain Ketoacid Dehydrogenase Subunit Genes
Authors: Price S. , Wang X.
Published: April 2003

Metabolic acidosis and glucocorticoids act in concert to stimulate branched-chain amino acid (BCAA) oxidation in adrenalectomized rats. In muscles of normal rats, metabolic acidosis increases the maximal activity of the rate-limiting enzyme, branched-chain α-ketoacid dehydrogenase (BCKAD) and a genetic response to catabolic conditions like uremia is implicated by concurrently higher levels of BCKAD subunit mRNA. To determine if acidification or glucocorticoids increase transcription of BCKAD subunit genes, transfection studies were performed with BCKAD promoter-luciferase reporter minigenes in LLC-PK1 cells which do not express gluco-corticoid receptors or LLC-PK1 cells which express a rat glucocorticoid receptor gene (LLC-PK1-GR101). Acidification significantly increased luciferase activity in LLC-PK1 cells and LLC-PK1-GR101 cells transfected with reporter plasmids containing 7.0 kb of E2 subunit or 0.8 kb of E1α subunit promoter region, respectively. Glucocorticoids in the form of dexamethasone induced transcription of these minigenes but only in LLC-PK1-GR101 cells. Using promoter deletion analysis, independent transactivation response elements to acidification or glucocorticoids were localized in the E2 promoter. In summary, catabolic responses to low extracellular pH and glucocorticoids include enhanced expression of genes encoding BCKAD subunits.
Pathophysiologic Glomerulotubular Growth Factor Link
Authors: Wang Shi-Nong , LaPage Janine , Hirschberg Raimund
Published: April 2003

Circumstantial evidence from clinical and pathologic correlations in patients with glomerular diseases and proteinuria suggest that glomerular protein ultrafiltration contributes to tubulointerstitial injury. A series of studies was performed to examine the hypothesis that in rats with adriamycin-induced nephropathy or with diabetic nephropathy (but not in normal rats) high molecular wt. growth factors are ultrafiltered into tubular fluid and act on tubular cells through apical membrane receptors. Analysis of proximal tubular fluid that was collected by nephron micropuncture indicates ultrafiltration of IGF-I, TGF-β and HGF. Respective receptors are also expressed in apical membranes in some parts of the nephron as examined by immunohistochemistry. In vitro cell culture experiments using proximal tubular fluid obtained from rats with experimental glomerular diseases indicate that ultrafiltered IGF-I may contribute to increased distal tubular Na-absorption. Indirect evidence also suggests that this growth factor may increase the secretion of collagen types I and IV in proximal tubular cells. TGF-β and HGF cause increased expression and basolateral secretion of MCP-1 in proximal tubular and collecting duct cells. There may be other biologic effects on tubules that are caused by apical exposure to ultrafiltered growth factors. These studies suggest that the glomerular ultrafiltration of bioactive proteins causes or contributes to tubulo-interstitial pathology in glomerular proteinuria.
Vitamin Replacement Therapy in Renal Failure Patients
Authors: Makoff Rhoda
Published: April 2003

Renal failure patients require vitamin replacement therapy that addresses the specialized needs of renal failure. Four factors including restricted diet, uremic toxins, drug-nutrient interactions, and in ESRD, the dialysis process, affect the normal absorption, retention and activity of necessary micronutrients which support all aspects of carbohydrate, protein, lipid and nucleic acid metabolism. Studies have shown that the typical renal failure diet is low in B vitamins, that uremic factors affect folate and pyridoxine activities and that many B vitamins are lost on dialysis at a rate greater than are lost with normal urinary excretion. In addition, retention of vitamin A or inappropriately high supplementation of vitamin C may cause toxicities which exacerbate existing pathologies. Further, emerging research suggests some vitamins such as folic acid and pyridoxine, if provided in higher than normal amounts, may have an impact on reducing the risk of some aspects of renal cardiovascular disease. It is therefore important to supplement some vitamins, and use restraint in the supplementation of others. It is clear that renal failure patients, including predialysis, ESRD and transplant patients need specialized supplementation that meets the requirements of disease and its management.
Liver Cell Reactive Components in Peritoneal Dialysis Fluids
Authors: Riegel Werner , Ulrich Christof , Friedrichsohn Christian , Paßlick-Deetjen Jutta , Kohler Hans
Published: April 2003

Metabolic changes in peritoneal dialysis (PD) patients are an important aspect concerning long-term outcome. Liver plays the main role in regulating metabolism. The effects of peritoneal dialysis fluids (PDF) on liver cell function are scarcely investigated. Therefore, we investigated the effects of PDF, different in some components, on liver cell metabolism in vitro. Metabolic activity (MTT), cell integrity (LDH release), proliferation (BrdU incorporation) and synthesis of albumin and transferrin are measured by incubating HepG2 cells for 3 h and 24 h with six different PDFs: (a) lactate-buffered, pH5.5: PDF I (1.5% gluc.); PDF II (4.5% gluc.); (b) bicarbonate-buffered, pH7.4: PDF III (1.5% gluc.), PDF IV (4.5% gluc.); (c) amino acid-based solutions, pH 7.4: PDF V (low AA level) and PDF VI (high AA level). Metabolic activity of bicarbonate-treated cells is greatly enhanced in comparison to lactate-buffered PDFs. These findings are confirmed by proliferation data. Synthesis of albumin and transferrin is significantly enhanced by amino acid-based solutions. Our data demonstrate, that lactate-buffered PDF impair liver cells much stronger than bicarbonate-buffered PDF. pH is the parameter which contributes to cytotoxicity and impaired metabolism to a major extent. In contrast to glucose-containing solutions, amino acid-based PDF stimulate protein synthesis in liver cells.
Advanced Glycation End-Product Levels in Subtotally Nephrectomized Rats: Beneficial Effects of Angiotensin II Receptor 1 Antagonist Losartan
Authors: Šebeková Katarina , Schinzel Reinhard , Münch Gerald , Krivošíková Zora , Dzúrik Rastislav , Heidland August
Published: April 2003

The angiotensin II receptor 1 antagonist losartan (L) inhibited the advanced glycated end-products (AGEs) induced expression of transforming growth factor β1 in in vitro experiments performed on renal tubuloepithelial cells. To test the pathophysiological importance of these findings, the possible link between serum AGEs levels and angiotensin system was investigated in the model of normotensive subtotally nephrectomized rats(4/6-NX). Concentration of AGEs in serum of placebo administered 4/6-NX rats (n = 7, 1.09±0.09 U/l) increased slightly in comparison with sham-operated healthy controls (CTRL, n = 8, 0.94±0.10 U/l, p<0.02) as measured by competitive ELISA. Treatment of 4/6-NX rats with L over 12 weeks ameliorated the rise in serum AGEs concentration (1.00±0.12 U/l, n = 15 <0.005) almost to the level observed for CTRL. This effect was further corroborated by the observation, that the impaired renal excretion of AGEs in 4/6-NX-placebo rats (0.07±0.02 U/µmol creatinine) was significantly restored by L (0.09±0.02 U/µmol creatinine, <0.009) and resembled that of the CTRL (0.10±0.03 U/µmol creatinine). Administration of L to 4/6-NX rats significantly improved renal function as evaluated by a smaller rise in serum creatinine and urea concentration. In spite of the improvement in renal function, there were no differences in concentrations of transforming growth factor β1 in serum and in urine among the two groups. These effects were independent of blood pressure. Our data give first evidence, that long-term treatment with angiotensin II receptor 1 antagonist may exert salutary effects on AGEs levels in the rat remnant kidney model, probably due to improved renal function.
Long, Slow Dialysis
Authors: Charra B. , Chazot C. , Jean G. , Laurent G.
Published: April 2003

Long slow hemodialysis (3×8 hours/week) has been used in Tassin for 30 years without significant change in the method. It provides excellent results in terms of morbidity and mortality. The better survival than usually reported on shorter dialysis is mainly due to lower cardiovascular mortality. The nutritional state of the patient is good, as well as the correction of anemia with low doses of EPO. But the main feature concerns blood pressure; hypertension is very well controlled without need for antihypertensive medications. The gentle ultrafiltration provided by a long session time associated with a low salt diet and a moderate interdialytic weight gain allows for normalization of the extracellular fluid space in most patients (dry weight) without important intradialytic morbidity. This low salt diet has paradoxically been forgotten in recent years while shortened dialysis time renders it more necessary than ever.
Nutritional Status Assessment and Body Composition Analysis in Pre-End Stage Renal Disease Patients
Authors: Dumler Francis , Kilates Christina
Published: April 2003

Malnutrition is a known risk factor for survival in renal failure patients. Of concern, a significant degree of malnutrition may develop in the predialysis period due to dietary restrictions and uremia. To further define this issue, we evaluated 25 predialysis patients using serum chemistries, body mass index (BMI), fat free mass (FFM), body cell mass (BCM), and protein appearance rate (PAR) as surrogates of nutritional status and compared their results to those obtained in established hemodialysis patients and recipients of living donor renal allografts during a nine-month observation period. Pre- dialysis patients had significantly (p<0.0001) higher body weight (28%), body mass index (26%), body cell mass (17%) and fat free mass (15%) than hemodialysis and transplant patients. Intracellular water content was similar in all groups. As many patients do not start dialysis until clearance values fall below 10 ml/min, it is possible that greater tissue mass losses occur in the weeks preceding initiation of dialytic therapy. Why renal transplant recipients fail to increase tissue mass may relate to the catabolic effects of immunosuppression. We conclude that the early stages of pre-end stage renal disease are associated with relatively good preservation of body cell mass.
Fiber Connections of the Nucleus isthmi in the Carp (Cyprinus carpio) and Tilapia (Oreochromis niloticus)
Authors: Xue Hao-Gang , Yamamoto Naoyuki , Yoshimoto Masami , Yang Chun-Ying , Ito Hironobu
Published: April 2003

The nucleus pretectalis (NP) is a prominent nucleus in the percomorph pretectum and has been shown to project to the nucleus isthmi in the filefish by an HRP tract-tracing method [Ito et al., 1981], but a homologous nucleus to the NP is apparently lacking in ostariophysans. The present study examined fiber connections of the nucleus isthmi in an ostariophysan teleost, the carp (Cyprinidae, Cyprinus carpio), to identify a nucleus homologous to the percomorph nucleus pretectalis. Identical studies in a percomorph tilapia (Cichlidae, Oreochromis niloticus) were also performed. Injections of biotinylated dextran amine (BDA) or biocytin to the carp nucleus isthmi labeled cells in the ipsilateral optic tectum and nucleus ruber of Goldstein [1905]. Labeled tectal neurons were located in the stratum periventriculare (SPV) and the stratum fibrosum et griseum superficiale (SFGS). The somata in the SPV were pyriform and those in the SFGS were fusiform. No labeled cells were found in the pretectum. Labeled terminals were seen in the ipsilateral nucleus pretectalis superficialis pars parvocellularis (PSp), optic tectum, and bilateral nucleus ruber. Terminals in the nucleus ruber appear to come from tectal neurons in the SFGS labeled by isthmic injections. Thus the nucleus isthmi has reciprocal fiber connections with the ipsilateral optic tectum, receives projections from the ipsilateral nucleus ruber, and projects to the ipsilateral PSp. The nucleus pretectalis homologue is apparently absent in the carp. Studies in tilapia showed that the nucleus isthmi receives bilateral projections from the NP and optic tectum. In addition, the present study revealed a previously unknown afferent from the nucleus ruber to the percomorph nucleus isthmi. The tilapia nucleus isthmi projects to the same targets as in the carp. Isthmic projection neurons in the tilapia optic tectum were located in the SPV and pyriform with a similar shape to the carp SPV neurons that project to the nucleus isthmi. No labeled cells were found in the SFGS of tilapia optic tectum. The fusiform neurons in the SFGS of the carp optic tectum possess various hodological similarities with the NP and may correspond to the NP neurons of percomorphs.
Urinary Sodium and Potassium Excretion in Idiopathic Hypercalciuria of Children
Authors: Polito Cesare , La Manna Angela , Maiello Rita , Nappi Barbara , Siciliano Maria Carmen , Di Domenico Maria Rosaria , Di Toro Rosario
Published: April 2003

Background: An increased spot urine Na/K ratio (UNa/K) has been found to be related to urinary stone disease in adults with a history of nephrolithiasis and in children with idiopathic hypercalciuria (HC). However, the respective role played by Na and K excretion in the rise of the UNa/K in growing individuals is not well clarified. Methods: The urinary excretion of Na and K was evaluated in fasting morning and 24-hour urine samples of 37 consecutive children with HC and of 21 previously HC children who were normocalciuric at the time of the study (ExHC). None of them had received any dietary or specific drug prescription. Results: In the HC and in the ExHC group, respectively, the Na excretion was 4 ± (SD) 2.4 and 2.9 ± 1.3 mmol/kg/day (p = 0.009); the K excretion was 1.1 ± 0.4 and 1.2 ± 0.7 mmol/kg/day (p = 0.86); the fasting UNa/K was 3 ± 1.6 and 2.1 ± 1 mmol/mmol (p = 0.044), and the 24-hour UNa/K was 4.2 ± 3.9 and 2.8 ± 1.5 mmol/ mmol (p = 0.045). The 24-hour UNa/K was significantly higher than the fasting UNa/K in both HC (p = 0.002) and ExHC (p = 0.002) subjects. The 24-hour UNa/K significantly increased with age in both HC (p = 0.02) and ExHC (p = 0.015) children. The K excretion significantly decreased with age in HC (p = 0.0001) and ExHC (p = 0.005) subjects, as well as with body weight gain in HC (p = 0.005) and ExHC (p = 0.0001) children and with increasing body height in HC (p = 0.006) and ExHC (p = 0.001) subjects. In neither group was the K excretion significantly related to body mass index Z score nor to height Z score. No significant relation resulted between Na excretion and age, body weight and height, and body mass index Z score and height Z score. Conclusions: HC children have a higher Na excretion as well as a higher fasting and 24-hour UNa/K than ExHC children, but no different K excretion. Meals are accompanied by a significant rise in UNa/K. The rise in UNa/K with age is mostly due to a decrease in K excretion which possibly depends on childhood body growth.
Randomized Trial of Methylcobalamin and Folate Effects on Homocysteine in Hemodialysis Patients
Authors: Trimarchi Hernán , Schiel Amalia , Freixas Emilio , Díaz Marisa
Published: April 2003

Background: There are no data available on the effects of intravenous (i.v.) methylcobalamin (Me-Cbl), the coenzymatically active form of vitamin B12 that acts as a cofactor for methionine synthase in the conversion of total homocysteine (tHcy) to methionine, with or without oral folic acid (FA) supplementation, on fasting tHcy levels in hemodialysis (HD) patients. Methods: We performed a prospective randomized trial in which 62 chronic HD patients without previous vitamin supplementation were divided into four groups. Group A received Me-Cbl 500 µg twice/week plus FA 10 mg/day; group B received FA 10 mg/day alone; group C received no vitamin supplementation, and group D was on Me-Cbl 500 µg twice/week alone. Fasting tHcy, vitamin B12, serum (s) FA and erythrocytic (e) FA were measured predialysis before and after 4 months of therapy. Results: Final tHcy levels were significantly lower in group A (10.2 ± 3.1 µmol/l) compared to groups C (27.3 ± 9.7 µmol/l, p < 0.001) and group D (24.3 ± 11.8 µmol/l, p < 0.001) and similar to group B (11.2 ± 1.9 µmol/l, p = n.s.). Mean tHcy levels showed a significant decrease in group A from 22.5 ± 15.6 to 10.2 ± 3.1 µmol/l (p = 0.003) and in group B from 19.9 ± 4.0 to 11.2 ± 1.9 µmol/l (p = 0.012), while no significant changes were observed in groups C (25.9 ± 9.3 vs. 27.3 ± 9.7 µmol/l, p = n.s.) and D (26.6 ± 14.3 vs. 24.3 ± 11.8 µmol/l, p = n.s.). Conclusion: Oral FA (10 mg/day) supplementation appears to be an effective approach to normalize plasma tHcy in chronic HD patients; the addition of i.v. Me-Cbl (500 µg twice/week) to this regimen showed no benefit. Separately, FA corrected hyperhomocysteinemia (HtHcy), while Me-Cbl showed no change.
Urinary Excretion of Aquaporin-2 Water Channel in Diabetic Ketoacidosis
Authors: Kusaka Ikuyo , Saito Takako , Nakamura Tomoatsu , Nagasaka Shoichiro , Ishibashi Shun , Ishikawa San-e
Published: April 2003

We studied the changes in plasma arginine vasopressin (AVP) and urinary excretion of aquaporin-2 (UAQP-2) water channel in 3 patients with diabetic ketoacidosis. They had marked hyperglycemia of 27.9 ± 2.8 mmol/l (mean ± SEM), and elevated hemoglobin A1c of 8.8 ± 1.4%. Circulatory blood volume was decreased by approximately 25%, which was determined by the changes in hematocrit. Plasma AVP levels were elevated to 10.3 ± 3.0 pmol/l and UAQP-2, 578 ± 200 fmol/mg creatinine (normal, 153 ± 28) at the hospitalization. When hyperglycemia was improved by the intravenous infusion of a small dose of insulin plus fluid administration, both plasma AVP and UAQP-2 promptly decreased to 1.2 ± 0.2 pmol/l and 252 ± 29 fmol/mg creatinine on day 7, respectively. These alterations were concomitant with the recovery of circulatory blood volume. In the present study, UAQP-2, in addition to plasma AVP, indicates circulatory blood volume depletion, and the changes in UAQP-2 estimates the AVP-dependent recovery of circulatory blood volume during the therapeutic period in the patients with diabetic ketoacidosis.
Relationship of Body Iron Stores to Levels of Serum Ferritin, Serum Iron, Unsaturated Iron Binding Capacity and Transferrin Saturation in Patients with Iron Storage Disease
Authors: Beutler Ernest , Felitti Vincent , Ho Ngoc J. , Gelbart Terri
Published: April 2003

None of the methods for assessing total body iron burden in patients with hemochromatosis is satisfactory. Although it is commonly believed that a relationship exists between serum ferritin levels and total iron burden, the extent of this relationship has not previously been documented. In the present investigation we measured the total body iron burden of 88 patients with putative hemochromatosis, 54 of whom were homozygotes for the 845G→A (C282Y) mutation. The total body iron stores were estimated from the volume of red cells removed during therapeutic phlebotomy corrected for an estimated 2 mg/day dietary iron absorbed during the phlebotomy period; the amount of storage iron was compared to the serum ferritin, serum iron, unsaturated iron binding capacity, and transferrin saturation before the beginning of phlebotomy. The serum ferritin proved to be the best predictor of body iron stores. The correlation between all of the analytes and the body iron burden was greater in patients homozygous for the C282Y mutation than in those who were not, including the compound heterozygotes for C282Y and H63D. The body iron burden tended to be greater in patients homozygous for the C282Y mutation than the other patients at any other given ferritin level. We conclude that the serum ferritin level does provide some information regarding total iron burden but even in the case of C282Y homozygotes, the correlation is not very strong.
Verantwortung, Respekt und Mitgefühl: Eine Trias der Conditio humana in der philosophischen Tradition
Authors: Bernath Klaus
Published: April 2003

Leider besteht für diesen Artikel keine Zusammenfassung. Als Einstieg stellen wir den Textanfang zur Verfügung Mit diesem von unserem Jubilar formulierten Thema ist mir eine schwierige Aufgabe gestellt worden. Ob ich wohl diesen Wunsch wenigstens ansatzweise erfüllen kann? Genau gesehen, sind es gleich mehrere Aufgaben, die in dieser knappen Darstellung bearbeitet werden sollen. Da ist zunächst eine Klärung der drei Begriffe selbst. Dann ist zu fragen, ob sie wirklich eine Trias bilden,d.h. ob und wie sie sachlich zusammengehören. Schliesslich ist dann nach ihrer Verwurzelung in der philosophischen Tradition gefragt – und alle zusammen sollen auch etwas Wesentliches über die Conditio humana aussagen, wobei stillschweigend vorausgesetzt ist, dass diese überhaupt so im direkten Zugriff und rein aus sich selbst verständlich gemacht werden kann.
Human Auditory Steady-State Responses during Repeated Exposure to Hypobaric Hypoxia
Authors: Lucertini Marco , Verde Paola , De Santis Stefano
Published: April 2003

This study was aimed at evaluating the time course of auditory steady-state response (SSR) variations during two consecutive exposures to hypobaric hypoxia. Six normal subjects were examined in a hypobaric chamber at ground level. Then, they climbed to a simulated altitude of 17000 ft (5182 m), where SSRs were recorded after 6, 12, 18, 24 and 30 min. Thereafter, they breathed 100% O2 and SSRs were recorded after 2 min of reoxygenation. A second exposure to hypoxia followed, with SSR recordings after 6 and 12 min. Finally, the subjects returned to ground level for recovery recording. A phase shift of SSR sinus wave was observed at the beginning of both exposures to hypoxia, although in the first recording (i.e. at 6 min) during the first exposure, the result was not statistically significant. A slight SSR phase shift was still detectable on return to ground level. The central acoustic pathway involved in SSR genesis was probably the area which was found to be most sensitive to hypoxia, compared to other parts of the auditory apparatus (e.g. the cochlea). This data could suggest an impairment of compensation mechanisms when consecutive exposures to hypoxia are performed.
Characteristics of Tinnitus Induced by Acute Acoustic Trauma: A Long-Term Follow-Up
Authors: Mrena Roderik , Savolainen Seppo , Kuokkanen Juha T. , Ylikoski Jukka
Published: April 2003

We investigated the prevalence, characteristics and subjective perceived handicap caused by long-term tinnitus induced by acute acoustic trauma (AAT) in 418 former military conscripts. They had been treated between 1984 and 1989 because of AAT from exposure to impulse noise caused by firearm shooting. All 418 patients reported tinnitus after the AAT. At discharge from the military service, 122 (29%) still reported tinnitus. In 1999, of these 122 patients, 101 were reached and 66 still had tinnitus. The Tinnitus Handicap Questionnaire demonstrated various difficulties in life because of tinnitus, not attributable only to tinnitus loudness. Psychological factors also seem to play an important role. The effects of AAT and possible compensation have been evaluated so far mostly by audiometric findings, but in some cases tinnitus may be an even more serious threat to life satisfaction than mild hearing impairment.
The 27-bp Tandem Repeat Polymorphism in Intron 4 of the Endothelial Nitric Oxide Synthase Gene Is Not Associated with Coronary Artery Disease in a Hospital-Based Taiwanese Population
Authors: Hwang Juey-Jen , Tsai Chia-Ti , Yeh Huei-Ming , Chiang Fu-Tien , Hsu Kuan-Lih , Tseng Chuen-Den , Liau Chiau-Suong , Tseng Yung-Zu , Lai Ling-Ping
Published: April 2003

We studied whether the 27 base pair (bp) tandem repeat polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) gene was associated with coronary artery disease (CAD) in a hospital-based Taiwanese population. We included 219 consecutive patients who underwent coronary angiography at our institution. Two alleles, containing 4 (eNOS4a) and 5 repeats (eNOS4b), were identified after polymerase chain reaction amplifying intron 4 of the eNOS gene. The genotype frequencies for eNOS4b/b, eNOS4a/b and eNOS4a/a were 77.9, 21.5 and 0.6% in CAD subjects, and 80, 20 and 0% in control subjects (Fisher’s exact test, p = 0.90), respectively. The odds ratio (OR) for CAD in patients with at least one eNOSa allele was 1.2 (0.5–2.9) after adjustment for classical CAD risk factors. The eNOS4a allele was not associated with the severity of CAD (Fisher’s exact test, p = 0.90) and the occurrence of acute myocardial infarction (AMI) or unstable angina (adjusted OR 0.6, 0.3–1.6) in patients with CAD. In conclusion, the 27-bp repeat polymorphism of the eNOS gene was not associated with CAD and the occurrence of AMI or unstable angina in a hospital-based Taiwanese population.
Nicotinamide Modulates Mitochondrial Membrane Potential and Cysteine Protease Activity during Cerebral Vascular Endothelial Cell Injury
Authors: Chong Zhao Zhong , Lin Shi-Hua , Maiese Kenneth
Published: April 2003

Microvascular endothelial cell (EC) apoptosis or programmed cell death (PCD) during free radical injury may be involved in the development of cerebral ischemic and degenerative diseases. Yet, the cellular mechanisms that mediate cerebral EC injury require further definition. We therefore used the agent nicotinamide as an investigative tool in EC cultures to examine the role of free radical nitric oxide (NO)-induced PCD. EC injury was evaluated by the trypan blue dye exclusion method, DNA fragmentation, membrane phosphatidylserine (PS) exposure, cysteine protease activity, mitochondrial membrane potential, and mitogen-activated protein kinase phosphorylation. We demonstrate that cerebrovascular PCD consists of two distinct pathways that involve the degradation of genomic DNA and the exposure of membrane PS residues. Each of these pathways is reversible in nature and is controlled independently by caspase 8, caspase 1, and caspase 3. As a cytoprotectant, nicotinamide is novel in the vascular system and functions at two levels. Nicotinamide not only maintains the mitochondrial membrane potential and the prevention of cytochrome c release, but also prevents the induction of caspase-8-, caspase-1- and caspase-3-like activities linked to the DNA repair enzyme poly(ADP-ribose) polymerase through mechanisms that are independent from the MAP kinase systems of p38 and JNK. The work begins to identify therapeutic strategies for the protection of the cerebral vasculature during both acute and chronic degenerative disorders.
Neuroendocrine Neoplasms of the Larynx: Diagnosis, Treatment and Prognosis
Authors: Ferlito Alfio , Shaha Ashok R. , Rinaldo Alessandra
Published: April 2003

The authors discuss the terminology, classification, diagnosis, treatment and prognosis of neuroendocrine neoplasms of the larynx.
Comparison of Side Effects of Levofloxacin versus Other Fluoroquinolones
Authors: Carbon Claude
Published: April 2003

The side-effect profile of levofloxacin was compared with that of other fluoroquinolones based on European and international data from approximately 130 million prescriptions. Levofloxacin was found to be very safe with a low rate of hepatic abnormalities (1/650,000). In contrast, 140 trovafloxacin-treated patients developed hepatic problems, 14 of which were severe, and 8 required transplantation. The main CNS problems associated with fluoroquinolones include dizziness, convulsions, psychosis, and insomnia. Levofloxacin, ofloxacin, and moxifloxacin reportedly have the lowest potential of inducing central nervous system (CNS) adverse events among the fluoroquinolones currently available. Cardiovascular problems were seen in 1/15 million levofloxacin prescriptions compared to 1–3% of sparfloxacin patients having QTc prolongation of greater than 500 msec. Moxifloxacin was also associated with QTc prolongation when compared to non-fluoroquinolone comparators. Nausea, vomiting, and diarrhoea remain the main adverse drug reactions (ADRs) associated with levofloxacin. However, the ADR rate for levofloxacin is still one of the lowest of any fluoroquinolone at 2% (compared to 2–10% for other fluoroquinolones). Ofloxacin and levofloxacin have a very low phototoxic potential, whereas this is a problem for sparfloxacin, enoxacin, and pefloxacin. The tolerance profile of levofloxacin can be considered to be very good, and better than most, if not all of the fluoroquinolones available.
Peak Systolic Velocity Doppler Index Reflects Most Appropriately the Dynamic Time Course of Intact Cerebral Autoregulation
Authors: Rosengarten B. , Kaps M.
Published: April 2003

Background: Transcranial Doppler sonography measures blood flow velocity in basal cerebral vessels with high accuracy and time resolution. Dynamic blood flow tests were used to investigate functional integrity of the cerebral autoregulation (CA) mechanism. It is known from cortical activation studies that velocity indices differ in their appropriateness to measure changes in blood flow velocity. We aimed to compare the peak systolic, enddiastolic and time-averaged mean flow velocity indices for their use in measuring the effectiveness of the CA mechanism. Methods: We performed the leg cuff test to induce in 15 healthy volunteers (aged 24.8 ± 0.4 years, 9 males) CA due to a sudden arterial blood pressure decrease. Data from the middle and posterior cerebral arteries were measured continuously with transcranial Doppler ultrasound, and the arterial blood pressure with a noninvasive photoplethysmographic method. After transforming all variables to relative changes, velocity-pressure diagrams were calculated for each velocity-pressure index. Additionally, we calculated the autoregulation index. Results: The step decrease in arterial blood pressure resulted in an initial drop, which is followed by a rapid recovery of cerebral blood flow velocity. The autoregulation index was 5.5 ± 1. Efficacy of CA is illustrated more accurately by peak systolic velocity-pressure curves, which lie continuously above a passive velocity-pressure relationship assuming CA to be absent. Conclusions: Our data show peak systolic blood flow velocity index to be most accurate for measuring effectiveness of the dynamic CA mechanism. No differences in the CA were found between the vascular territory of the middle and posterior cerebral arteries.
Recurrent Pontine Base Infarction: A Controlled Study
Authors: Kim Jong S.
Published: April 2003

Objectives: To assess the clinical features of and risk factors for recurrent pontine base infarction. Methods: This study includes 5 patients with unilateral pontine base infarction who developed another infarction on the opposite side and, for comparison, 10 follow-up period-matched patients with unilateral pontine base infarction who did not develop recurrent pontine infarction. MRI and angiogram studies were performed in all cases. The two groups were compared. Results: The patients with recurrent pontine base infarction developed quadriparesis, dysarthria and dysphagia. MRI showed bilateral infarcts abutting on the basal surface of the pons. Angiogram studies revealed diseased basilar artery in 3 patients. There were no differences regarding age, gender, angiogram findings and frequency of hypertension, diabetes mellitus, cigarette smoking and hypercholesterolemia between the patients with recurrent stroke and those without. However, the former had a significantly higher number of risk factors for atherosclerosis (p < 0.05) and higher frequency of coronary heart disease (p < 0.05) than the latter. Conclusions: The number of risk factors for atherosclerosis and a concomitant presence of coronary heart disease may be factors related to recurrent pontine base infarction in patients with unilateral pontine infarction. The main pathogenesis of recurrent pontine base infarction seems to be basilar artery branch atherothrombosis.
Effects of Glucose and Fluoride on Competition and Metabolism within in vitro Dental Bacterial Communities and Biofilms
Authors: Bradshaw D.J. , Marsh P.D. , Hodgson R.J. , Visser J.M.
Published: April 2003

Antimicrobial effects of fluoride in vivo remain contentious. Previous studies suggested that 1 mM NaF reduced acid production from glucose, and prevented the enrichment of bacteria associated with caries in a chemostat model. The present study examines the effects of a lower fluoride concentration (0.53 mM, 10 ppm NaF) in both biofilm and planktonic microbial communities. Nine oral species were grown at pH 7.0 and pulsed on 10 successive days with glucose; bacterial metabolism was allowed to reduce the pH for 6 h before being returned to neutrality, either in the presence or absence of NaF. In addition, 10-day-old mixed culture biofilms were overlaid with glucose, with or without NaF, and the pH change followed by microelectrode. After 10 days, chemostat pH dropped to ca. pH 4.5 following glucose pulses, and the community was dominated by Streptococcus mutans (rising from 4 to 23% of total CFU) and Veillonella dispar (16 to 73%). In comparison, after 10 days pulsing with glucose + fluoride, the final pH was significantly higher (ca. pH 4.9) (paired t test, p < 0.0001). The culture was predominated by V. dispar (70%) and Actinomyces naeslundii (13%), whereas S. mutans proportions were significantly lower (t test, p = 0.04), remaining <3% of the total flora, compared to the culture without fluoride. Biofilm pH fell to only pH 5.55 1 h after glucose/fluoride overlay, compared to 4.55 with glucose alone (paired t test, p < 0.000001). Analysis of the data suggests that fluoride exerts dual antimicrobial modes of action. Fluoride prevents enrichment of S. mutans by inhibiting critical metabolic processes (direct effect) and, in an inter-related way, by reducing environmental acidification (indirect effect) in biofilms.
Effect of Amine Fluoride Toothpaste and Gel in High Risk Groups of Hungarian Adolescents: Results of a Longitudinal Study
Authors: Madléna Melinda , Nagy Gábor , Gábris Katalin , Márton Sándor , Keszthelyi Gusztáv , Bánóczy Jolán
Published: April 2003

The aim of the study was to establish a preventive program with the combined use of amine fluoride toothpaste and gel in groups of adolescents living in different locations in Hungary. Caries and oral hygiene examinations were performed at the beginning of the study and repeated after 1 and 2 years. The adolescents were divided into 3 groups: 1 control and 2 test groups. The control group continued its usual oral care habits. One of the test groups received Elmex toothpaste for unsupervised home use daily and Elmex gel for use once a week, and the other test group received Elmex toothpaste and only placebo gel. The combined use of amine fluoride-containing toothpaste and gel provided a significant reduction in DMFS mean values (38% including white spot lesions, 34% not including white spot lesions, p < 0.05) and in visible plaque index values (18%, p < 0.05) compared to the control group.
Decreased Photodamage and Low Incidence of Non-Melanoma Skin Cancer in 136 Sun-Exposed Caucasian Patients with Vitiligo
Authors: Schallreuter Karin U. , Tobin Desmond J. , Panske Angela
Published: April 2003

Background: It is well established that ultraviolet radiation is related to non-melanoma skin cancer (NMSC) in Caucasians. Considering that patients with vitiligo have often no protective pigment in sun-exposed depigmented/white skin together with severe oxidative stress due to accumulation of millimolar epidermal hydrogen peroxide (H2O2), it would be expected that these patients develop a higher risk for early photodamage and NMSC. However, scattered reports on low patient numbers documented no increased risk for sun-induced skin cancers in this disease. Objective: The aim of this study was to validate the possible photodamage and the development of epidermal neoplasia in a randomly selected larger patient group with emphasis on each patient’s sun sensitivity and the history of solar habits. Furthermore we wished to compare histological signs for epidermal photodamage in a random representative patient group (mean age >30 years) and age-matched healthy controls. Methods: One hundred and thirty-six randomly selected patients (females n = 93; males n = 43; mean age 42.4 years, range 14–70 years) were included in this study. To assess signs of photodamage and skin cancer, all patients underwent a thorough full-body examination by Wood’s light and dermatoscopy. In order to learn about each patient’s individual sun sensitivity and solar habits, a direct questionnaire was used. In addition full skin punch biopsies of sun-exposed depigmented/pigmented skin were taken under local anaesthesia and evaluated by light microscopy. Results: There was no evidence for sun-related damage in the entire patient group, despite a significant number of positive cases with a history of sunburns in early childhood and continuous accumulation of epidermal H2O2. Histological examination of the epidermis showed no signs of increased photo-ageing and confirmed the absence of apoptosis in these patients. Furthermore surprisingly there was no increased risk for photosensitivity disorders, i.e. polymorphous light reaction, solar urticaria and acute actinic dermatitis. Conclusion: The results of this study confirm in a large group of patients with vitiligo the absence of an expected high risk for sun-induced damage and skin cancer. Based on these results together with a recent report on increased functional wild-type p53 expression in these patients we would like to propose that in vitiligo there may be a direct association between this important tumour suppressor and the absence of photodamage and NMSC.
Safety and Efficacy of Combined High-Dose Treatment with Calcipotriol Ointment and Solution in Patients with Psoriasis
Authors: van de Kerkhof P.C.M. , Green C. , Hamberg K.J. , Hutchinson P.E. , Jensen J.K. , Kidson P. , Kragballe K. , Larsen F.G. , Munro C.S. , Tillman D.M.
Published: April 2003

Background: In the vast majority of psoriatic patients, psoriatic lesions are localised on the body as well as on the scalp. Therefore, safety data on the combined use of calcipotriol in lotion and calcipotriol in ointment are needed. Objective: This study investigated the effect of high-dose treatment with a combination of calcipotriol ointment and scalp solution on calcium metabolism, indices of bone turnover and PASI in patients with extensive psoriasis. Methods: Following a 2-week wash-out period, 88 patients were randomised to 4 weeks of treatment with either calcipotriol ointment/scalp solution (80–100 g/week and 30–50 ml/week, respectively; n = 41) or with a dithranol/tar regimen (n = 47). Patients were seen at weeks 1, 2 and 4 during treatment and 1 week following cessation of treatment. Results: No significant differences at the end of treatment were found between the 2 groups with respect to 24-hour urinary excretion of calcium (expressed as calcium/creatinine ratio), phosphate or pyridinoline, serum concentrations of calcium (albumin corrected), creatinine, phosphate, parathyroid hormone, 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, osteocalcin, alkaline phosphatase (total and bone-specific iso-enzymes) or 1-collagen telopeptide. At the end of treatment, the psoriasis area and severity index had decreased by 57.4% in the calcipotriol group and by 36.1% in the dithranol/tar group (p = 0.004). Investigators’ and patients’ assessments of overall efficacy also favoured treatment with calcipotriol (p < 0.001). Conclusion: The combined use of calcipotriol ointment/scalp solution did not affect the indices of calcium metabolism or bone turnover and was significantly more effective than dithranol/tar in reducing disease severity and extent in patients with extensive psoriasis.
Japanese Speech Therapy (Logopedics) Education after the Presentation of the Education Guidelines in the 1995 IALP General Assembly
Authors: Iitaka Kyoko
Published: April 2003

The background of the education system for Japanese speech therapists (logopedists) is reported. It took nearly 40 years for speech therapists and medical doctors to come to a consensus in order to define the status and educational system for the 1997 Law for Japanese Speech Therapists. Unfortunately, the IALP Education Guidelines of 1995 received little respect in the process of long negotiation. The present situation and the future goals for Japanese speech therapists are discussed.
Treatment Program Planning by Speech Therapists in Taiwan
Authors: Tseng Chin-Hsing , Wen Yi-Chang
Published: April 2003

Speech-language pathology is a rapidly growing profession in Taiwan. To assess its autonomy and maturity, a survey on the treatment program with the help of a 14-item questionnaire was conducted among 90 speech therapists from health care settings. Questions about the planning of the treatment program, its components, and the employed therapeutic methods were addressed in the study. The survey findings helped clarify the current role of speech therapists in Taiwan.
Inverse Correlation between Insulin-Like Growth Factor (IGF)-Binding Protein-5 and IGF-I and II during Postnatal Development of the Anterior Pituitary Gland
Authors: González-Parra Silvia , Rosato Roberto R. , Chowen Julie A. , Argente Jesús , Groffen Cora , Dits Natasja , Drop Stenvert L.S.
Published: April 2003

Background: The insulin-like growth factor (IGF) system is important for pituitary development and control, with each member of this axis having a specific temporal and spatial expression. Because IGF-binding protein-5 (IGFBP-5) is one of the most highly expressed binding proteins in the anterior pituitary (AP), it might be of special importance in this gland. Objective: The purpose of this study was to examine the temporal relationship between the expression of the IGFs and IGFBP-5 in the AP during postnatal development. Design and Methods: Quantitative reverse transcription polymerase chain reaction was used to study the mRNA levels of these proteins in the AP of male and female rats at 10, 20, 30, 40 and 60 days of age. Results: The highest mRNA levels of IGF-I and II occurred at 10 and 20 days of age with a dramatic decrease at 30 days (p < 0.0001). IGF-I, but not IGF-II, mRNA levels increased again during adulthood (60 days). The pattern of IGFBP-5 mRNA was inversely expressed, with maximum values occurring at 40 days. IGF-I mRNA levels were higher in males at 10 days, but higher in females at 20 days. The expression of IGF-II was higher in males both at 10 and 20 days. IGFBP-5 gene expression was higher in females at 40 days. Conclusion: The dramatic changes in the expression of IGF-I, IGF-II and IGFBP-5 throughout postnatal development suggest that these factors play important roles in the development of this gland and that their actions are highly interrelated.
Graves’ Disease Presented as Painful Goiter
Authors: Chao Chen-Shun , Lin Shih-Yi , Sheu Wayne Huey-Herng
Published: April 2003

Pain in the thyroid gland is rarely present in Graves’ disease. We describe a 32-year-old female hyperthyroid Graves’ disease patient with an initial manifestation of painful goiter. On physical examination, the thyroid gland was diffusely enlarged and tender. The laboratory examinations showed high serum thyroid hormone and low thyrotropin values. Serum inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate, were elevated. Thyroid ultrasound revealed multiple focal hypoechoic areas. All these findings gave an initial impression of an acute inflammatory and destructive process in the thyroid gland. However, subsequent thyroid scintigraphy demonstrated a diffuse radioactive iodide uptake pattern with positive serum thyrotropin receptor antibodies. Fine-needle aspiration cytology showed only the presence of lymphocytes. She was diagnosed as having Graves’ disease and was treated with propylthiouracil, and prednisolone was given for neck pain. Within a few days, the thyroid tenderness dramatically improved, and the erythrocyte sedimentation rate progressively normalized. However, follow-up thyroid function tests still showed high serum thyroid hormone levels. The possible etiologies of a painful thyroid gland in Graves’ disease will be discussed.
‘Suppressed’ Double Adenoma – A Rare Pitfall in Minimally Invasive Parathyroidectomy
Authors: Zettinig Georg , Kurtaran Amir , Prager Gerhard , Kaserer Klaus , Dudczak Robert , Niederle Bruno
Published: April 2003

Since the introduction of a quick intraoperative parathyroid hormone (QPTH) assay, complete removal of hyperfunctioning parathyroid tissue can be proven during surgery. We report on a scintigraphically and biochemically documented patient with persistent primary hyperparathyroidism (PHPT) caused by suppressed hyperfunctioning parathyroid tissue. A left lower enlarged parathyroid gland was resected by minimally invasive open parathyroidectomy. QPTH measurements confirmed complete resection of hyperfunctioning tissue and histology showed a tumorous enlarged left lower parathyroid gland. The patient was normocalcemic until 1 month after surgery, when serum calcium increased again. A MIBI scan 6 months after surgery showed no evidence of hyperfunctioning parathyroid tissue. After an increase of PTH, a third MIBI scan another 3 months later was performed. Increased tracer uptake behind the lower pole of the right thyroid lobe was seen and confirmed by ultrasonography. Another tumorous enlarged parathyroid gland was removed. These findings support the hypothesis that smaller yet abnormal parathyroid glands can be suppressed and may become hypersecretory if left in situ after surgical removal of the larger gland.