bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Prolonged Corticosteroid Therapy on the Outcome of Steroid-Responsive Nephrotic Syndrome
Authors: Matsukura Hiro , Inaba Susumu , Shinozaki Kentaro , Yanagihara Toshio , Hara Masanori , Higuchi Akira , Takada Tsuneo , Tanizawa Takakuni , Miyawaki Toshio
Published: April 2003

Eighty-six patients (59 males and 27 females) diagnosed with steroid-responsive nephrotic syndrome during childhood were identified. The patients were 20–40 years of age (mean 27.0 ± 5.0) with a mean follow-up period of 19.5 ± 5.9 years. All patients had been treated with a long-term tapering corticosteroid therapy. Thirty patients had also received a course of cyclophosphamide (2 mg/kg/day for 12 weeks). Sixty-six had achieved sustained remission off corticosteroids, while 20 were still receiving corticosteroids to maintain remission. None of the 86 patients had proteinuria or renal insufficiency at the time of the study. Mean final heights in males and females were similar (–0.51 ± 1.21 and –0.23 ± 1.16 standard deviation score). Mean final height of 20 steroid-dependent patients was significantly less than that of 66 in remission off corticosteroids (p < 0.005). Ten cyclophosphamide-treated patients got married and 9 had at least 1 healthy child. In children with steroid-responsive nephrotic syndrome, the need for corticosteroid therapy to maintain remission may be associated with decreased adult height. Patients who received a 12-week course of cyclophosphamide are likely to be normally fertile as adults.
Ultrastructural ‘Fingerprint’ in Cryoprecipitates and Glomerular Deposits: A Clinicopathologic Analysis of Fingerprint Deposits
Authors: Su Cheng-Fang , Chen Han-Hsiang , Yeh Jui-Chi , Chen Shiu-Ching , Liu Chuan-Chuan , Tzen Chin-Yuan
Published: April 2003

Organized glomerular electron-dense deposits with a fingerprint pattern are well known in some patients of lupus nephritis or cryoglobulinemia. In general, these two diseases are always discussed separately as the causes of such deposits. However, 3 of our 5 lupus patients with glomerular fingerprint deposits also had cryoglobulinemia. One of the remaining 2 patients died and the other was lost to follow-up. The purpose of our study was to seek an appropriate clinicopathologic assessment of fingerprint deposits. All these patients showed overt proteinuria, active urinary sediment, a high degree of activity of lupus nephritis, and diffuse proliferative glomerulonephritis (WHO class IV). Their cryoprecipitates and renal biopsy specimens were investigated by means of immunochemistry, immunofluorescence and electron microscopy. The ultrastructural ‘fingerprint’ structures were exactly the same in the cryoprecipitates and in the glomerular deposits in 2 of 3 lupus patients with cryoglobulinemia, as were IgG, IgM and IgA. Therefore, these observations furnish emerging morphologic evidence for the glomerular deposition of immune complexes of circulating cryoglobulins in lupus nephritis. In addition, electron microscopic fingerprint deposits on renal biopsy or cryoprecipitate can be regarded as a very sensible marker of concomitant or subsequent development of diffuse lupus nephritis. If the patient is accompanied by nephritic syndrome, an early trial of immunosuppressive therapy may be warranted.
Downregulation of Vascular Endothelial Growth Factor and Its Receptors in the Kidney in Rats with Puromycin Aminonucleoside Nephrosis
Authors: Fan Liying , Wakayama Tomohiko , Yokoyama Shigeru , Amano Osamu , Iseki Shoichi
Published: April 2003

Aim: We aimed to examine the possible involvement of vascular endothelial growth factor (VEGF) in the pathogenesis of puromycin aminonucleoside nephrosis (PAN). Methods: The expression and localization of the mRNA of VEGF and its receptors, flt-1 and flk-1, were analyzed in the kidneys of puromycin aminonucleoside-injected rats by use of Northern blotting and in situ hybridization. Results: In association with the induction of proteinuria, VEGF mRNA underwent decrease in amount from 3 days after the injection, reaching the minimum level at 7 days, followed by a gradual recovery by 28 days. The levels of flk-1 and flt-1 mRNA showed similar transient decrease in PAN kidney, whereas the mRNA of von Willebrand factor, a marker of endothelial cells, showed no change in amount. In the normal rat kidney, VEGF mRNA was localized primarily to podocytes, and flk-1 mRNA was localized exclusively to endothelial cells with much higher intensity in glomeruli than in peritubular capillaries. In PAN kidney, the intensities of both VEGF and flk-1 signals in podocytes and glomerular endothelial cells, respectively, appeared much lower at 7 days than in normal kidney. Conclusion: These results indicate that the VEGF-VEGF receptor system is downregulated in PAN, implying that it is not involved in the mechanism of proteinuria in PAN.
Blebs in the Mouse Cerebellar Granular Layer as a Sign of Structural Inhomogeneity
Authors: Hawkes R. , Gallagher E. , Ozol K.
Published: April 2003

When the adult mouse cerebellum is perfusion-fixed with 70% ethanol, paraffin-embedded, sectioned, and the sections are rehydrated, the granular layer wrinkles into an elaborate array of blebs. In the posterior lobe vermis these blebs are seen in both transverse and sagittal sections, are symmetrical about the midline, reproducible between neighboring sections and between individuals, and bear a constant relationship to the Purkinje cell bands as revealed by zebrin II immunocytochemistry. The data suggest that blebs represent individual cytoarchitectonic units and thus that the mouse cerebellum is subdivided into several thousand modules, each comprising >102 Purkinje cells and their associated interneurons and glial cells.
Hereditary Dominance of Fast-Twitch Fibers in Skeletal Muscles and Relation of Thyroid Hormone under Physiological Conditions in Rats
Authors: Suwa M. , Miyazaki T. , Nakamura T. , Sasaki S. , Ohmori H. , Katsuta S.
Published: April 2003

To investigate whether muscle fiber compositions of various skeletal muscles were correlated with each other and whether muscle fiber type composition was related to the serum thyroid hormone level, fast-twitch fiber dominant rats (FFDR), which had a higher percentage of fast-twitch (FT) fibers in the deep portion of the lateral head of the gastrocnemius muscle (GAS), were compared to a control group. The FFDR group was obtained by the selective breeding for high-percentage FT fibers in the GAS, and the control group was obtained by random breeding from the same base population. The percentages of FT fibers of the GAS, soleus (SOL), vastus intermedius (VI), biceps brachii (BB), rectus abdominis (RA) and extensor digitorum longus (EDL) muscles were analyzed. The percentages of FT fibers of the GAS, SOL, VI and BB in the FFDR group were significantly higher than in the control group (p<0.05), and percent FT fibers of the GAS were significantly correlated with those of the SOL (r = 0.62, p<0.01), VI (r = 0.45, p <0.05) and BB (r = 0.43, p<0.05). On the other hand, no significant differences between FFDR and the control group and no significant correlations with the GAS were observed in percent FT fibers of the RA and EDL. The total 3,3′,5-triiodo-L-thyronine (T3) level in FFDR was not significantly different from the control group and was not significantly correlated with the percentage of FT fibers. These data suggest that the percentages of FT fibers of various skeletal muscles are genetically correlated with each other, but some FT muscles are not because they might be close to the upper limits of the genetic adaptive range. In addition, percentages of FT fibers are independent of the total T3 level under physiological conditions.
Anatomical Description and Frequencies of Bony Projections on the Cerebral Aspect of the Petromastoid Part of the Temporal Bone in Dry Adult Human Skulls
Authors: Choudhry R. , Tuli A. , Choudhry S. , Kakar S. , Raheja S.
Published: April 2003

A morphological peculiarity was observed in the form of bony projections on the upper part of the medial border of the groove for the sigmoid sulcus on the internal surface of the mastoid part of the temporal bones. In a study on 636 temporal regions of 318 dry unsexed adult human skulls of Indian origin, 101 (15.9%) temporal bones exhibited these elevations. These ranged from being inconspicuous tubercles to well-defined sharp spines. In 73 (72.3%) cases, a projection was present unilaterally, more commonly on the right side and in 28 (27.7%) it was bilateral. A subjective assessment of the size showed the projections to be small (70; 69.3%), medium (16; 15.8%) and large (15; 14.8%).
Recent Advances in the Molecular Genetics of Hereditary Retinal Dystrophies with Primary Involvement of the Macula
Authors: Weber B.H.F.
Published: April 2003

Hereditary dystrophies of the central retina and choroid are a heterogeneous group of disorders characterized by preferential loss of macular function and consequently loss of central and color vision. The primary causes leading to the degenerative processes are largely unknown although recent progress in human molecular genetics is most promising in providing novel insights into the basic biochemical mechanisms of these dystrophies. To date, the disease loci of more than 20 maculopathies including cone and cone-rod dystrophies have been mapped to specific chromosomal regions of which seven disease genes have already been identified. As the goals of the Human Genome Initiative approach completion, the cloning of the genes involved in the etiology of human retinopathies will be greatly simplified providing the basis for a more comprehensive understanding of retinal function and dysfunction. In addition, these advances will facilitate the identification of individuals at risk at a presymptomatic or initial stage of disease, thus creating a unique opportunity to devise novel therapeutic strategies that will primarily be aimed at an early intervention with the potential to either delay or even prevent the development of disease pathology.
Impaired Function of Bipolar Cells in the Royal College of Surgeons Rat
Authors: Hanitzsch R. , Zeumer C. , Lichtenberger T. , Wurziger K.
Published: April 2003

The retina of the Royal College of Surgeons (RCS) strain of rat, which is being used as an animal model for human retinal degenerations, has been employed in the study of the function of second order neurons. By about the 33rd postnatal day the dendritic branching of isolated bipolar cells is more sparse than in bipolar cells of the normal rat retina, but their GABA channels are as in the normal rat retina. The normally occurring light-induced distal potassium increase has been used as the indicator of the functional competence of second order neurons in the isolated RCS rat retina. These are dependent upon the integrity of ionotropic and metabotropic synapses. At about the 22nd postnatal day MgCl2 enlarges the light-induced distal potassium increase in the young RCS rat retina as in the normal rat retina. It seems that MgCl2 does not block the metabotropic synapses of on-bipolar cells. At about postnatal day 33, at which time the photoreceptors of the RCS rat retina had become severely damaged, the size of this light-induced distal potassium increase was not changed, but it was abolished by MgCl2. This indicates that bipolar cells are still active but that the synaptic function of on-bipolar cells has become vulnerable to MgCl2. The conclusion is that at a time when photoreceptor degeneration is already severe bipolar cells are still active, but that on-bipolars, mainly rod bipolar cells, have some functional deficit.
Complex Movement Patterns: Modifiability and Constraints
Authors: Bout R.G.
Published: April 2003

Most behaviours involve complex morphological systems and vice versa morphological systems are used by the organism in many different ways. During evolution and ontogeny changes in kinematics and function of skeletal and muscular systems must be coordinated with changes in their neural control. Neuromotor patterns are sometimes believed to be conserved in evolution, leading to diversification at the level of musculoskeletal design. Vertebrate motor patterns used in feeding are reviewed to examine this hypothesis. Stereotyped behaviour is not necessarily the result of phylogenetic constraints but may also result from the functional demands imposed by the mechanics of the jaw apparatus and the nature of the task performed. Sensory feedback and descending control not only contribute to ‘online’ control of movement but also shape the development of motor patterns and learning behaviour and indicate a potentially large flexibility. The neural and sensory apparatus that produces this flexibility will be subject to evolutionary modification. In the absence of a demand for flexibility motor patterns may become stereotyped in some species, while they are very flexible in others. To the extent that morphological systems perform independent movements during different behaviours, separate basic motor patterns may be required, which may be coordinated in different ways.
Immunological Evaluation of Patients with Beta-Thalassemia major
Authors: Consolini Rita , Calleri Angelica , Legitimo Annalisa , Massei Francesco
Published: April 2003

Abnormalities in the immune system and zinc homeostasis in patients with β-thalassemia major (TM) have been reported. Since zinc ion is essential for the efficiency of the immune system and is required to induce biological activity to thymulin (Zn-FTS), a biochemically defined thymic hormone, we investigated the plasma levels of zinc and both active thymulin (Zn-FTS) and total zinc saturable thymulin (Zn-FTS+FTS) in 18 patients with TM aged between 2 and 31 years and 22 normal controls of the same age. Inhibitory molecules anti-thymulin and the distribution of lymphocyte subsets were also analyzed. Patients with TM presented significantly lowered plasma zinc and thymulin levels when compared to normal subjects. The significant enhancement of the active form of the hormone after zinc addition in vitro suggests that low thymulin values found in TM are due not to a thymic failure in synthesizing and secreting the thymic hormone, but a defect in zinc saturation of the hormone. An impairment of cell subset distribution was also demonstrated. This study shows that zinc and thymulin deficiency contribute to the complex mechanisms underlying immune dysfunction in TM.
Non Hypoxia-Related Splenic Infarct in a Patient with Sickle Cell Trait and Infectious Mononucleosis
Authors: Symeonidis Argiris , Papakonstantinou Christos , Seimeni Urania , Sougleri Maria , Kouraklis-Symeonidis Alexandra , Lambropoulou-Karatza Chrysoula , Vagenakis Apostolos , Zoumbos Nicholas
Published: April 2003

Splenic infarction in patients with sickle cell trait is usually related to hypoxic conditions, while non-hypoxia-related infarcts are extremely rare. We report on a case of a 17-year-old male patient, living at sea level, who developed a severe left upper quadrant abdominal pain during the course of a febrile episode. On physical examination he had a mildly palpable but extremely painful spleen. A spleen scan revealed 2 areas of impaired radionucleide distribution. Hepatic enzymes were moderately increased and the IgM anti-EBV antibodies positive. Hemoglobin electrophoresis revealed the presence of 42% of hemoglobin S. A probable diagnosis of splenic infarction was established in a patient with sickle cell trait, during the course of infectious mononucleosis. The patient was treated symptomatically. The conditions of splenic congestion induced by the EBV infection and the high-grade fever may have contributed to splenic sequestration and subsequent infarcts.
Factors Determining the Actual Received Dose Intensity in a Program of Multicyclic Dose-Intensive Alternating Chemotherapy with Sequential Stem Cell Support
Authors: Pérez-Calvo Javier , Martínez-Aguillo Maite , García-Rayo Susana , Ramón y Cajal Teresa , Santisteban Marta , Ordóñez Jose Manuel , Inogés Susana , Subirá Maria Luisa , Martín-Algarra Salvador , Brugarolas Antonio
Published: April 2003

Dose intensity has been related to clinical outcome in several solid tumors. We studied the influence of clinical and cellular parameters on dose intensity received in a series of 53 patients with metastatic breast cancer or advanced ovarian cancer. They received courses of cisplatin 120 mg/m2 plus etoposide 600 mg/m2 alternating every 14 days with ifosfamide 8 g/m2 plus paclitaxel 200–350 mg/m2. Blood stem cell support was administered after every course except for the first one. Patients with excellent mobilization underwent immunomagnetic selection of CD34+ cells. We found a significant inverse correlation between the CD34+ cell dose infused and the delay for the administration of the next cycle. A CD34+ cell dose between 1.5 and 5 × 106/kg per cycle was found to be feasible and was followed by a median delay of 1day (not different from doses above 5 × 106/kg). Three factors independently predicted the actually received dose intensity in a multiple regression model (R2 = 0.4): previous autologous transplantation, eligibility for immunomagnetic selection (excellent response to mobilization) and median CD34+ cell dose received along the treatment.
Stem Cell Factor: Biology and Relevance to Clinical Practice
Authors: Smith M.A. , Pallister C.J. , Smith J.G.
Published: April 2003

The type III tyrosine kinase receptor c-KIT and its ligand stem cell factor (SCF; also known as KIT ligand, mast cell growth factor and steel factor) are closely involved in the regulation of a wide range of tissues at different stages of life. This review provides an outline of the discovery, structure and expression of SCF and c-KIT but concentrates on their respective roles in the regulation of human haemopoiesis and how this knowledge might be exploited in the clinical setting.
Direct-Antiglobulin-Test-Negative Immune Haemolytic Anaemia and Thrombocytopenia in a Patient with Hodgkin’s Disease
Authors: Kondo Haruki , Oyamada Takashi , Mori Akinori , Sumi Hajime , Kurosu Katsushi , Kajii Eiji , Mikata Atsuo
Published: April 2003

A case of direct-antiglobulin-test (DAT)-negative auto-immune haemolytic anaemia (AIHA) and immune thrombocytopenia (ITP) associated with Hodgkin’s disease (HD) is reported. A 52-year-old male was admitted with anaemia, thrombocytopenia, and lymphadenopathy. The patient was DAT negative, although he exhibited the clinical features of warm-type AIHA and elevated levels of red-blood-cell-associated IgG (RBC-IgG). The serum level of platelet-associated IgG (PA-IgG) was markedly increased. A biopsy specimen of the inguinal lymph nodes showed HD of mixed cellularity. Marked improvement of subjective symptoms, normalization of haematological values and a decrease in the level of both RBC- and PA-IgG were observed after the start of combination chemotherapy for HD. Although the association of HD, ITP, and/or AIHA has been infrequently reported, the measurement of RBC-IgG is recommended in cases of HD with anaemia even though DAT is negative, since HD is known to be associated with various protean immunological abnormalities.
Primary Hepatic Burkitt’s Lymphoma with Chronic Hepatitis C
Authors: Kuroda Junya , Omoto Atsushi , Fujiki Hiroshi , Okugawa Kaori , Tamai Hidemasa , Yamagishi Hisakazu , Kobayashi Yutaka , Yoshikawa Toshikazu
Published: April 2003

The liver is an uncommon primary site for malignant lymphoma, and primary hepatic lymphoma has been found to make up 0.4% of all extranodal lymphomas. We report a rare case of a 75-year-old Japanese male with primary hepatic Burkitt’s lymphoma, according to both the revised European-American Lymphoma classification and the new World Health Organization classification. As not only histological findings but also immunological features are deemed essential in the diagnosis of Burkitt’s lymphoma, the previous 7 cases of primary hepatic Burkitt’s lymphoma were not fully evaluated, using these criteria. As far as we know, this is the first case of primary hepatic Burkitt’s lymphoma with typical features on histological, immunological and cytogenetical analysis. He had a history of chronic hepatitis C over several decades with subsequent liver cirrhosis. From our review of the literature and our case, the relationship between hepatitis C virus infection and the development of primary hepatic Burkitt’s lymphoma remains obscure.
Ten-Year Survivor with Multiple Myeloma in First Complete Remission following Treatment with Conventional Chemotherapy
Authors: Abe Rokuo , Ishibashi Toshiyuki , Shichishima Tsutomu , Maruyama Yukio
Published: April 2003

A 62-year-old woman with multiple myeloma, who has been in complete remission (CR) for 10 years, is reported. The patient was treated with conventional chemotherapy, including nitrosourea derivatives. Five patients with myeloma, including the present case, who have survived for 10 years or more in CR and on whom detailed clinical descriptions were published, are reviewed. Their disease condition represented ‘a cure’ or ‘a state extremely close to cure’. The review indicates the following favorable prognostic factors common to these patients: age ≤65 years and a rapid response to treatment. Progressive bone destruction and/or lytic changes at disease onset is perhaps not a bad prognostic factor in myeloma patients with excellent outcome.
The Picture of Inflammation: A New Concept That Combines the White Blood Cell Count and Erythrocyte Sedimentation Rate into a New Hematologic Diagnostic Modality
Authors: Rotstein Rivka , Fusman Renato , Zeltser David , Shapira Itzhak , Shabtai Esther , Avitzour Dani , Sadees Nicole , Levartovsky David , Arber Nadir , Eldor Amiram , Berliner Shlomo
Published: April 2003

Background: Physicians who work in small clinics, far away from medical centers, cannot obtain relevant information regarding the acute phase response at low cost and real time. Methods: We adopted a simple slide test and image analysis to determine the number of white blood cells in the peripheral blood, their degree of adhesiveness/aggregation as well as that of the red blood cells. Three independent observers scored the images into categories of no (1), mild (2), moderate (3) or severe (4) inflammation. Results: A substantial interobserver agreement was noted for all three observers. No patient classified as having no (1) inflammation was given a score of moderate (3) or severe (4) inflammation and vice versa. The one-way analysis of variance (age- and gender-adjusted) confirmed that the data obtained from the image analyzer are significantly different between the above-mentioned four categories. Conclusions: It is possible to use a simple slide test and image analysis to discriminate effectively between various degrees of inflammation intensity. Since it is possible to send the pictures via telephone, Inter- or Intranet to a physician somewhere else, it might be attractive for medical personnel who work in small clinics not equipped with sophisticated laboratory facilities. This technique is currently being evaluated for possible Telemedicine and E-Health uses.
Leukaemic Transformation in a Case of Thrombocythaemia
Authors: Quaglino Dennis , Di Leonardo Gabriella , Stati Massimo
Published: April 2003

The authors describe a case of thrombocythaemia, with subsequent leukaemic transformation. Cytochemical and immunocytochemical investigations indicated a trilineage involvement of the myeloid series, compatible with a leukaemic transformation at the level of the colony-forming unit granulocytes, erythrocytes, macrophages, megakaryocytes. No cytogenetic abnormalities were observed. The criteria which have been proposed to differentiate essential thrombocythaemia from pre-fibrotic thrombocythaemia, as an early phase of idiopathic myelofibrosis, are discussed. The differentiation is not only of academic interest but has relevant practical implications, since survival in the two conditions is significantly different. The possible significance of an accompanying monoclonal gammopathy is discussed.
An Alu Insert as the Cause of a Severe Form of Hemophilia A
Authors: Sukarova E. , Dimovski A.J. , Tchacarova P. , Petkov G.H. , Efremov G.D.
Published: April 2003

Alu sequences represent a specific human family of interspersed repetitive DNA, with a copy number in excess of 500,000 within the human genome. Alu repeats are rarely present in protein-coding regions of mature RNA, and only a few Alu insert mutations have been described so far. In this paper we present an Alu retroposition event in a family with a severe form of hemophilia A. The inserted Alu element belonging to the youngest Yb8 subfamily disrupts the reading frame at methionine 1224, exon 14 of the factor VIII gene, leading to a stop codon within the inserted sequence. This observation indicates that the retroposition of Alu elements is a continuing process possibly generating various human genetic defects.
Effect of Cerivastatin on Urinary Albumin Excretion and Plasma Endothelin-1 Concentrations in Type 2 Diabetes Patients with Microalbuminuria and Dyslipidemia
Authors: Nakamura Tsukasa , Ushiyama Chifuyu , Hirokawa Kaoru , Osada Shiwori , Shimada Noriaki , Koide Hikaru
Published: April 2003

Background/Aims: To determine whether cerivastatin, a newly developed novel synthetic potent statin, exerts a renoprotective effect, we assessed urinary albumin excretion (UAE) and plasma and urinary endothelin (ET)-1 concentrations in normotensive microalbuminuric type 2 diabetes patients with dyslipidemia. Methods: Sixty normotensive type 2 diabetic patients (38 men and 22 women; mean age 56.5 years) with microalbuminuria (20–200 µg/min) and dyslipidemia (total cholesterol >200 mg/dl, LDL cholesterol >160 mg/dl, HDL cholesterol <35 mg/dl, and triglyceride >150 mg/dl) were enrolled in a double-blind study for 6 months, receiving either cerivastatin (0.15 mg/day) or placebo. Plasma and urinary ET-1 concentrations were measured by radioimmunoassay. Results: Cerivastatin did not affect serum creatinine and HbA1c levels, and reduced systolic blood pressure slightly, but not significantly. Plasma levels of total cholesterol and LDL cholesterol were significantly reduced (p < 0.01), and plasma triglyceride levels were also reduced significantly (p < 0.05) after 6 months of cerivastatin treatment. A concomitant significant decrease in UAE (p < 0.01), and urinary and plasma ET-1 concentrations (p < 0.01) were found during this period. Conclusion: The use of cerivastatin is associated with decreased microalbuminuria and plasma and urinary ET-1 levels in microalbuminuric patients with type 2 diabetic mellitus and speculate that this may represent an amelioration of renal injury.
Minimal Change Glomerulonephritis following a Wasp Sting
Authors: Zaman F. , Saccaro S. , Latif S. , Atray N. , Abreo K.
Published: April 2003

We report the case of a young white male who developed the nephrotic syndrome after being stung by a wasp. A percutaneous renal biopsy was done revealing minimal change glomerulonephritis. The patient was treated with oral prednisone with resolution of proteinuria. Corticosteroids were gradually tapered, the patient did not experience a relapse, and remains in good health with normal renal function. Herein, we also include a review of the literature on wasp bite associated nephrotic syndrome in patients who underwent a renal biopsy.
Increased Incidence of Tuberculosis in Chronic Hemodialysis Patients
Authors: Kürşat Seyhun , Özgür Bülent
Published: April 2003

We encountered 9 cases of tuberculosis out of our 157 chronic HD patients in 36 months. Four pulmonary, 4 lymph nodal and one isolated dermal involvement were detected. Therapy was commenced without waiting for absolute cultural or pathologic diagnosis because of the high index of clinical suspicion. All cases except one recovered completely. Among associated conditions, peptic ulcer disease, anti-HCV positivity, and diabetes mellitus were noted, though the last two did not reach statistical significance. Prompt institution of the specific therapy and close supervision of the cases during treatment enabled us to obtain a cure in all cases except one and to discern adverse drug effects immediately and to make appropriate changes in the therapy. Thus, no morbidity due to the disease itself or drugs was observed.
CAPD-Associated Peritonitis Caused by Alcaligenes xylosoxidans sp. xylosoxidans
Authors: Tang Sydney , Cheng Chi Chung , Tse Kai Chung , Li Fu Keung , Choy Bo Ying , Chan Tak Mao , Lai Kar Neng
Published: April 2003

Alcaligenes xylosoxidans is an uncommon cause of peritonitis in patients on maintenance continuous ambulatory peritoneal dialysis (CAPD). Peritonitis caused by A. xylosoxidans usually carries a poor prognosis because of the pathogen’s virulence and its universal resistance to most antimicrobial agents. Even after early Tenckhoff catheter removal, the transport property of the peritoneum is often irreversibly damaged, leading to permanent technique failure. We report 2 patients with CAPD-associated peritonitis due to A. xylosoxidans sp. xylosoxidans who were successfully cured with a combination of piperacillin and tazobactam. One of them subsequently returned uneventfully to CAPD.
Homocysteine-Lowering Effect of 500 μg Folic Acid Every Other Day versus 250 μg/Day
Authors: Brouwer I.A. , van Rooij I.A.L.M. , van Dusseldorp M. , Thomas C.M.G. , Blom H.J. , Hautvast J.G.A.J. , Eskes T.K.A.B. , Steegers-Theunissen R.P.M.
Published: April 2003

Background/Aims: Elevated plasma total homocysteine (tHcy) concentrations are a risk factor for neural tube defects and vascular diseases. Supplementation with folic acid decreases tHcy. We investigated whether supplementation with 500 µg folic acid every other day is as effective in lowering tHcy as 250 µg folic acid each day. Methods: In a 4-week intervention study, 22 healthy young women (18–40 years old) took either 500 µg folic acid every other day (500-µg/2d group) or 250 µg folic acid each day (250-µg/d group). Fasting blood was collected on days 0 and 28. Results: Plasma folate concentrations increased by 11.4 nmol/l (6.8–15.9) in the 250-µg/d group and by 9.1 nmol/l (95% Cl 1.9–16.3) in the 500-µg/2d group. These increases were not significantly different from each other. THcy concentrations decreased by 1.52 µmol/l (95% Cl –2.09 to –0.95; p < 0.001) in the 250-µg/d group and by 0.88 µmol/l (–1.53 to –0.23; p < 0.05) in the 500-µg/2d group. The difference in decrease between the 250-µg/d group and the 500-µg/2d group was 0.64 µmol/l (p = 0.11). Conclusion: Although not conclusive, this study suggests that supplying subjects with folic acid each day decreases tHcy more effectively than a double dose every other day.
Hypocholesterolemic Effect of Dietary Psyllium in Female Rats
Authors: Terpstra A.H.M. , Lapré J.A. , de Vries H.T. , Beynen A.C.
Published: April 2003

We fed cholesterol-enriched (1% cholesterol and 0.2% cholic acid) semipurified diets containing either 3% cellulose or psyllium to 2 groups of female Wistar rats for a period of 8 weeks. The feeding of the cholesterol-enriched semipurified diets resulted in a progressive increase in plasma cholesterol levels in both groups during the 8 weeks of the experiment. The rats fed psyllium, however, had significantly lower plasma cholesterol concentrations than the animals fed cellulose throughout the experimental period (at 8 weeks, 8.92 ± 4.42 and 16.47 ± 8 mmol/l, respectively, means ± SD, n = 14, p < 0.01). Most of the plasma cholesterol in both groups at the end of the study was located in the very low-density lipoprotein (VLDL) fraction (91%) and differences in total plasma cholesterol concentrations were predominantly reflected in differences in VLDL cholesterol. Plasma triglyceride concentrations were not significantly different between the 2 groups. Liver cholesterol concentrations paralleled the concentrations of plasma cholesterol and were significantly lower (p < 0.001) in the psyllium-fed rats (90.31 ± 13.81 µmol/g liver) than in the cellulose-fed rats (60.49 ± 15.25 µmol/g liver). Substitution of psyllium for cellulose resulted in an increase in the excretion of fecal bile acids by 26%, and this increase was predominantly caused by an increased excretion of β-muricholic acid and the bile acids derived from β-muricholic acid (ω-muricholic acid and hyodeoxycholic acid).
Influence of a Probiotic Yoghurt on the Status of Vitamins B1, B2 and B6 in the Healthy Adult Human
Authors: Elmadfa Ibrahim , Heinzle Cornelia , Majchrzak Dorota , Foissy Helmut
Published: April 2003

Background/Aims: The main reason for this study was to determine whether yoghurt bacteria, being rich in some water-soluble vitamins, release them or utilize vitamins from their surroundings. Our study was trying to determine for the first time, if the viable bacteria of probiotic yoghurt are able to influence the parameters of the B-vitamin (B1, B2, B6) status of the healthy adult human. Methods: The test yoghurt was commercially available probiotic yoghurt prepared with Streptococcus thermophilus and Lactobacillus acidophilus, enriched with Lactobacillus casei GG. Different chemical forms of all investigated B-vitamins were determined by HPLC methods. In order to determine the influence of the yoghurt flora, each of 12 subjects consumed four yoghurt portions 125 g each ( = 500 g) a day, containing thermally inactivated cultures during the first 2-week period and yoghurt without heat treatment during the second 2-week period. Results: The heat treatment of the probiotic yoghurt caused negligible changes in vitamin contents. The plasma levels of thiamin decreased significantly (p < 0.01) after the first 2-week period and kept on decreasing during the second 2-week period. A similar trend was found in the urinary excretion. The plasma levels of the B2-vitamers were different. The flavin adenine dinucleotide concentrations increased significantly (p < 0.01) after the consumption of heat-treated yoghurt and decreased significantly (p < 0.05) after the following 2 weeks, in which the subjects received the untreated yoghurt. In contrast, the flavin mononucleotide plasma levels decreased during the first 2-week period and increased during the second part of the study, but the change was not statistically significant. The free riboflavin concentrations in plasma and urine showed a continuous but not significant increase. The concentrations of pyridoxal-5-phosphate in plasma increased after the consumption of yoghurt with the inactivated bacteria and decreased in the second part of the study. However, the differences were not significant. The excretion of thiamin, B2- and B6-vitamers in the faeces did not significantly change throughout the study period (p > 0.05). Conclusions: Our observations show that the bacterial flora of the examined yoghurt does not influence the vitamin B1, B2 and B6 status of man. It seems likely that even lactobacilli of the ‘probiotic’ type which are vitamin B consumers can decrease the bioavailability of these vitamins for man. Obviously a thermal death of the cells did not induce a release of physiologically active vitamins.
Fat Absorption and Metabolism in Bile Duct Ligated Rats
Authors: De Vriese S.R. , Savelii J.L. , Poisson J.-P. , Narce M. , Kerremans I. , Lefebvre R. , Dhooge W.S. , De Greyt W. , Christophe A.B.
Published: April 2003

Background: Bile excretion is obstructed in children with extrahepatic bile duct atresia (EHBA) resulting in fat malabsorption and disturbed lipid metabolism. Aim: Investigate if the bile duct ligated rat exhibits similar deviations as patients with EHBA under different feeding conditions. Methods: 6 bile duct ligated Wistar rats and 12 matched paired controls were randomised over 3 feeding groups. Rats were killed 16 or 30 days postsurgery. Faeces, blood and livers were collected. Fat absorption was evaluated, markers for cholestasis and the fatty acid composition of serum phospholipids (PL) and cholesterol esters (CE) were determined. Fatty acid desaturation activities in liver microsomes were measured. Results: Cholestatic bile duct ligated rats have a lower fat absorption coefficient and a lower fraction of 18:2n–6 and 18:3n–3 in serum triglycerides than their controls. This demonstrates that bile duct ligated rats suffer from fat malabsorption. In contrast to the observations in serum triglycerides, 18:2n–6 and 18:3n–3 were not reduced in serum PL and CE of cholestatic rats. Overflow of 18:2n–6 rich biliary PL in the general circulation could contribute to this observation. In agreement with what was found in man, serum PL of cholestatic rats have a higher 16:0/18:0 ratio, increased monoenes and reduced unsaturated fatty acids. However, no differences were observed in microsomal desaturation activities. Conclusion: Cholestatic bile duct ligated rats exhibit similar deviations in serum fatty acid composition as found in patients with EHBA, therefore they can be used as a model for this human disease.
Use of the Pinna Reflex as a Test of Hearing in Mutant Mice
Authors: Cheatham Mary Ann , Pearce Malini , Richter Claus-Peter , Onodera Ko , Shavit Jordan A.
Published: April 2003

Although it is a gross measure, the pinna reflex test is easily administered and is, therefore, incorporated as a general screening tool in mutagenesis programs. Our recent application of this approach indicated that mutant mice lacking one of the small Maf proteins, in this case MafG, failed to exhibit a pinna reflex. In contrast, littermate controls, with the same mixed 129/CD1 background, and including both wild type and heterozygous mutant animals, passed the test. Because previous studies indicate that mafG is expressed in both cochlear and vestibular parts of the mouse inner ear, the source of this ‘presumed deafness’ was further assessed by making round window recordings to determine compound action potential thresholds. Auditory brainstem responses were also acquired to assess function along portions of the central auditory pathway. In all cases, responses in homozygous mutants (–/–) were comparable to those obtained from littermate controls, either wild type (+/+) or heterozygous mutants (+/–). Gross anatomy of the organ of Corti was also found to be similar in all three groups of mice. Hence, the lack of a pinna reflex must relate to nonauditory causes.
Overexpression of Copper/Zinc- Superoxide Dismutase Protects from Kanamycin-Induced Hearing Loss
Authors: Sha Su-Hua , Zajic Gary , Epstein Charles J. , Schacht Jochen
Published: April 2003

The participation of reactive oxygen species in aminoglycoside-induced ototoxicity has been deduced from observations that aminoglycoside-iron complexes catalyze the formation of superoxide radicals in vitro and that antioxidants attenuate ototoxicity in vivo. We therefore hypothesized that overexpression of Cu/Zn-superoxide dismutase (h-SOD1) should protect transgenic mice from ototoxicity. Immunocytochemistry confirmed expression of h-SOD1 in inner ear tissues of transgenic C57BL/6-TgN[SOD1]3Cje mice. Transgenic and nontransgenic littermates received kanamycin (400 mg/kg body weight/day) for 10 days beginning on day 10 after birth. Auditory thresholds were tested by evoked auditory brain stem responses at 1 month after birth. In nontransgenic animals, the threshold in the kanamycin-treated group was 45–50 dB higher than in saline-injected controls. In the transgenic group, kanamycin increased the threshold by only 15 dB over the respective controls. The effects were similar at 12 and 24 kHz. The protection by overexpression of superoxide dismutase supports the hypothesis that oxidant stress plays a significant role in aminoglycoside-induced ototoxicity. The results also suggest transgenic animals as suitable models to investigate the underlying mechanisms and possible strategies for prevention.
Epidemiology of Vascular Disease in Renal Failure
Authors: Ikizler T. Alp
Published: April 2003

Cardiovascular disease (CVD) is the leading cause of death in the general population and a major cause of morbidity and mortality chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. The high prevalence of CVD in incident dialysis populations suggests that CVD begins during or before the stage of chronic renal insufficiency. While traditional risk factors observed in the general population may play a role in the progression of CVD in CKD and ESRD patients, the presence of several nontraditional factors related to the extent of uremia seems to be the more significant feature of CVD in this patient population. Recently, there have been significant advances in our understanding of how inflammation contributes to the pathogenesis of atherosclerosis and myocardial infarction. The fact that chronic inflammation and CVD are highly prevalent in ESRD patients, it is probable that chronic inflammation may be a causative factor for accelerated atherosclerosis observed in CKD and ESRD patients. Given the extent of the problem, efforts to lower the mortality rate among ESRD patients will require new approaches to reduce and/or prevent cardiovascular morbidity and mortality.
Preventing Vascular Access Dysfunction: Which Policy to Follow
Authors: Besarab Anatole
Published: April 2003

In the USA, three Clinical Performance Measures are currently in place: increasing the number of autologous arteriovenous fistulas (AVFs) among incident hemodialysis patients to 50% and to 40% in prevalent hemodialysis patients; to foster the surveillance of accesses with pre-emptive correction of problems before accesses thrombose or fail, and to reduce the use of catheters in prevalent patients to less than 10%. Reduction of catheters will automatically result from initiatives that increase the construction of AVFs and pre-emptive monitoring and surveillance of accesses for dysfunction. Therefore, policies that promote the latter two vascular access aspects are most important to develop and follow. Of these two, however, the most impact will be made by promoting a policy to increase AVF creation in the timeliest manner possible. Strategies and resources needed to achieve these policies are presented. The need for a team approach is emphasized.
Perinatal Development of the Rat Kidney: Proliferative Activity and Epidermal Growth Factor
Authors: Okada Toshiya , Iwamoto Asako , Kusakabe Ken , Mukamoto Masafumi , Kiso Yasuo , Morioka Hiroshi , Sasaki Fumihiko , Morikawa Yoshio
Published: April 2003

The immunolocalization of proliferating cell nuclear antigen (PCNA), epidermal growth factor (EGF) and its receptor (EGFR) was examined in the perinatal rat kidney. As the index of proliferative activity, PCNA-positive cell ratios in glomeruli and proximal tubules were determined. The PCNA-positive ratios in both glomeruli and proximal tubules decreased significantly during the perinatal period and tended to decrease as the glomerular developmental stage proceeded as well. PCNA-positive cells were seen predominantly in the nephrogenic zone of the kidney throughout the period examined. They were noted in the collecting ducts of the nephrogenic zone and were rarely seen in those of the central zone of the kidney. On the other hand, PCNA-positive cells were noted in the straight portion of the proximal tubules and were rarely seen in the convoluted one. EGF-positive cells were seen in the proximal tubules, distal tubules and collecting ducts, though EGF-positive cells in the proximal tubules decreased after birth. EGFR-positive cells were seen along the entire length of the proximal tubules and collecting ducts as well as in immature glomeruli, not in mature ones. These results indicate that marked cell proliferation occurs in the collecting ducts in the peripheral area and in the proximal tubules in the central area of the kidney, that the proliferative activity decreases with age during the perinatal days and that EGF plays an important role in the proliferation of glomerular cells, and in both proliferation and maturation of the cells in the proximal tubules and collecting ducts.
Effects of Perinatal Hypoxia on Serum Unbound Free Fatty Acids and Lung Inflammatory Mediators
Authors: Weinberger Barry , Carbone Tracy , England Sandra , Kleinfeld Alan M. , Hiatt Mark , Hegyi Thomas
Published: April 2003

Cellular injury during tissue hypoxia is due, in part, to reactive intermediates released by activated leukocytes. We found that the inflammatory mediators tumor necrosis factor (TNF)-α, IL-6, and IL-1β are elevated in situ in lung macrophages on day 14 following exposure of rats to intermittent or chronic hypoxia from birth. Because inflammatory mediators can increase lipolysis in adipocytes, we also measured serum unbound free fatty acids (FFAu) – the biologically active compartment of FFA – in rat pups exposed to intermittent or chronic hypoxia. FFAu values were markedly elevated during the first 2 days of life in all rats, displaying an approximately 3-fold decrease from day 2 to day 3. Exposure to chronic hypoxia significantly increased FFAu levels measured on day 13. Since elevated serum FFAu are known to suppress leukocyte activation, we speculate that increased FFAu levels represent a mechanism for attenuating inflammation and tissue injury following sublethal hypoxia in the perinatal period, either physiologically in the immediate newborn period, or as a late response to ongoing hypoxic insult.
Disturbed Surface Properties in Preterm Infants with Pneumonia
Authors: Rüdiger M. , Friedrich W. , Rüstow B. , Schmalisch G. , Wauer R.
Published: April 2003

Congenital pneumonia in preterm infants is often associated with respiratory insufficiency requiring mechanical ventilation. This study was performed to show whether pneumonia in these infants is associated with an inhibition or deficiency of surfactant. The ratio of lecithin and sphingomyelin (L/S ratio) and minimal surface tension were determined in pharyngeal aspirates from 90 term born infants (healthy) and in tracheal aspirates from preterm infants with wet lung (n = 13), congenital pneumonia (n = 21) and respiratory distress syndrome (RDS) (n = 90). The L/S ratio was lower (p < 0.0001) in the RDS group (8.6) when compared with healthy (48.6), wet lung (42.9) and pneumonia (28.9). Surface tension was higher (p < 0.001) in RDS (37 mN/m) and pneumonia (33.7) when compared with healthy (22.9) or wet lung (21.2). For infants with RDS, L/S ratio <16.5 detects surfactant deficiency with 96% specificity and 70% sensitivity, surface tension >29 mN/m represents surfactant inhibition (specificity 97%, sensitivity 92%). Using these cut-off values in infants with pneumonia, 81% had a sufficient amount of surfactant but only 21% of infants with pneumonia had appropriate surface tension. Our study shows that lung effluent of respiratory insufficient infants with pneumonia, who need mechanical ventilation, has disturbed surface properties despite a sufficient amount of surfactant. In these infants, surfactant substitution could be beneficial.
Labor Pain Effects on Colostral Milk Beta-Endorphin Concentrations of Lactating Mothers
Authors: Zanardo Vincenzo , Nicolussi Silvia , Giacomin Carlo , Faggian Diego , Favaro Flaviano , Plebani Mario
Published: April 2003

β-Endorphin (β-EP) levels of colostral milk are approximately two-fold higher than in plasma of lactating women, in who concentrations peak at term, after the first and second stages of labor. We investigated the effect of labor pain and vaginal parturition on colostral β-EP concentrations (β-endorphin 125I RIA, Incstar Corp., Stillwater, Minn., USA) of at-term nursing mother, in comparison to those having undergone elective cesarean section. Our results show that colostral milk β-EP concentrations of mothers who delivered vaginally are significantly higher on the 4th postpartum day (6.0 ± 0.5 vs. 4.3 ± 0.4 pmol/l, respectively; p < 0.01) than colostral levels of mothers who underwent cesarean section. These data indicate the important influence of the labor process on the colostral opioid galactopoiesis. It is suggested that labor and parturition pain may increase colostral milk β- EP concentrations of lactating mothers in order to help the newborn overcome the stressful perinatal events of natural labor and delivery.