bluuebunny/crossref_metadata_2025_split huggingface dataset:
Granulocyte-Macrophage Colony-Stimulating Factor and Interferon-Alpha 2B in Patients with Advanced Renal Cell Carcinoma
Authors: Lümmen G. , Sperling H. , Luboldt H. , Otto T. , Rübben H. 
Published: April 2003

<b>Objective:</b> Biological response modifiers such as interferon-α2B (IFN-α2B) have well-known clinical activities against renal cell carcinoma (RCC). Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) has antitumorigenic effects both in vitro and in vivo. Therefore, a phase-I/II trial of IFN-α2B and GM-CSF was performed in patients with metastatic RCC. <b>Methods:</b> 21 patients in groups of 3 patients received GM-CSF at 7 different dose levels (15–300 μg) subcutaneously in combination with IFN-α2B at a fixed dose of 10 × 10<sup>6</sup> IU s.c. three times weekly for 12 weeks. <b>Results:</b> Two complete remissions have been observed, both with lung metastases only. With increasing dose levels of GM-CSF a slight tendency to more toxicity was detectable. Due to grade-3 toxicities 5 patients (24%) dropped out of the treatment schedule. Increases in WBC, neutrophils, lymphocytes, and monocytes were noted but were not related to the dose levels of GM-CSF. <b>Conclusions:</b> Results demonstrate that simultaneous administration of GM-CSF and IFN-α2B is tolerated up to doses of 120–150 μg GM-CSF three times weekly. But there is no additional antitumorigenic effect of GM-CSF because the overall response rate of the combined administration of GM-CSF/IFN-α2B is similar to IFN-α2B alone and there is no obvious dose relationship between increasing doses of GM-CSF and the responses.
Giant Retroperitoneal Hemangiopericytoma with Paraneoplastic Gynecomastia
Authors: Derakhshani P. , Neubauer S. , Braun M. , Heidenreich A. , Engelmann U. 
Published: April 2003

We report on a 38-year-old patient with a giant retroperitoneal hemangiopericytoma associated with bilateral paraneoplastic gynecomastia, which led to an almost uncontrollable hemorrhage on initial surgery due to the extreme hypervascularity of the process. After angiographic evaluation and superselective embolization, a complete surgical excision of a hemangiopericytoma weighing almost 1,000 g could be achieved. To reduce the risk of recurrence adjuvant radiotherapy with 49 Gy followed. Follow-up of 24 months showed no sign of recurrence on CT scans. To our knowledge this is the first reported case of hemangiopericytoma associated with a paraneoplastic syndrome. The literature and the therapeutic concepts are presented and discussed.
Therapy of Superficial Bladder Carcinomas
Authors: Otto T. , Krege S. , Noll F. , Rübben H. 
Published: April 2003

Treatment of superficial bladder carcinoma was derived by several large randomized trials. This group of cancers is stratified by differentiation grade and stage in three groups of different risk profiles (Ta G1-2 vs. T1 G1-2 vs. Tis/T1 G3). Standard therapy is fractionated transurethral resection (TUR). Adjuvant therapy after transurethral resection is not indicated in primary Ta G1-2 tumors because there is a low recurrence rate and no risk of tumor progression. The recurrence rate can be decreased up to 15% in recurrent Ta or T1 G1-2 tumors by intravesical therapy with mitomycin C (20 mg/instillation) or adriamycin (50 mg/instillation). Therapy should be limited to early (within 24 h post-TUR) and short-term treatment (4 × weekly, 5 × monthly). Alternatively, patients can be treated by intravesical BCG (strain Connaught or strain RIVM). Maintenance therapy is advantageous according to recurrence rate. Tumors with great malignant ability (Tis or T1 G3) will be treated initially with adjuvant BCG. Patients who fail are candidates for radical cystectomy within 3–6 months after initial diagnosis. There is no need – except in clinical trials – for the administration of unverified or not admitted drugs.
Diffuse Metastasized Testicular Teratoma and Paraneoplastic Thyreotoxicosis
Authors: Derakhshani P. , Klotz T. , Heidenreich A. , Engelmann U. 
Published: April 2003

Paraneoplastic syndromes are rare entities in patients with excessive HCG production. This has been attributed to the thyroid-stimulating hormone-like activity of HCG. In most cases hyperthyroidism remains subclinical. We report on a patient with diffuse metastasized malignant teratoma and thyreotoxicosis due to excessive levels of tumor-derived HCG. This complication of nonseminomatous germ cell tumors is associated with potential morbidity and the need for prompt recognition is stressed. Treatment consists of standard antithyroid medication and immediate cytoreductive chemotherapy to reduce the paraneoplastic stimulus. Evaluation of thyroid hormone levels in all patients with serum HCG levels exceeding 20,000 U/l is recommended.
Influence of α-Thalassemia Trait on the Prevalence and Severity of Anemia in Pregnancy among Women in Kuwait
Authors: Diejomaoh F.M.E. , Haider M.Z. , Dalal H. , Abdulaziz A. , D’Souza T.M. , Adekile A.D. 
Published: April 2003

α-Thalassemia is very common in the Kuwaiti population, but its influence on anemia of pregnancy has not been previously investigated. We have screened a group of 59 anemic (Hb <11 g/dl) pregnant women for the α-thal-2 (–α-3.7 kb) deletion which is the commonest α-thal allele in this community, using a polymerase chain reaction method. A control group of 35 nonanemic (Hb ≥11 g/dl) pregnant women was studied for comparison. All the women were in the second or third trimester of pregnancy. Among the 94 women in both groups, 69 (73.4%) had a normal complement of α-globin genes (αα/αα), 18 (19.1%) were heterozygotes (–α/αα) and 7 (7.4%) were homozygotes (–α/–α) giving an allele frequency of 17.0%. Among the anemic group, there were 44 (74.6%) individuals with a normal genotype, 9 (15.3%) heterozygotes and 6 (10.2%) homozygotes. In the nonanemic group, the corresponding prevalence figures were 25 (71.4%), 9 (25.7%) and 1 (2.9%), respectively. The difference between these distributions was statistically significant (χ<sup>2</sup> = 37.5, p < 0.0001). However, the mean Hb values were similar in heterozygotes, homozygotes and normal individuals. We, therefore, conclude that while the α-thal trait affects the prevalence of anemia among pregnant Kuwaiti women, it does not affect its severity.
Human Parvovirus B19 Capsid Antigen in Granulocytes in Parvovirus-B19-Induced Pancytopenia after Bone Marrow Transplantation
Authors: Kobayashi Shoichi , Maruta Atsuo , Yamamoto Toshiharu , Katayama Noriko , Higuchi Ryuko , Sakano Yoko , Fujita Hiroyuki , Koharazawa Hideyuki , Tomita Naoto , Taguchi Jun , Kodama Fumio , Nakamura Yoshiyasu , Shimizu Akio 
Published: April 2003

A patient with refractory anemia with an excess of blasts in transformation developed pancytopenia and a concurrent interstitial pneumonia 110 days after allogeneic bone marrow transplantation. Bone marrow examination showed 0.4% giant proerythroblasts and 86.2% granulocytes, some of them large with a bizarre configuration and the others of normal size. Serum folate level was found low, 0.6 ng/ml. Immunocytochemistry with a B19-specific monoclonal antibody MAB8292 revealed B19 capsid antigen only in erythroblasts and large, bizarre granulocytes, but not in granulocytes of normal size. In situ hybridization of bone marrow cells using digoxigenin-labeled DNA probes detecting parvovirus B19 also demonstrated positive signals in 8.5% of marrow cells. Parvovirus B19 DNA was isolated from the serum and the bronchoalveolar lavage fluid of this patient by the polymerase chain reaction. These findings suggest that neutropenia may be caused by an involvement with parvovirus B19 though a deficiency of folic acid may have in part contributed to the genesis of neutropenia in the patient. The relevance of parvovirus B19 to the interstitial pneumonia remains unclear.
Effect of Chronic Fluoride Exposure in Uremic Rats
Authors: Dunipace Ann , Brizendine Edward , Wilson Marie , Zhang Wu , Wilson Cynthia , Katz Barry , Kafrawy Abdel , Stookey George 
Published: April 2003

This study was conducted to test the hypothesis that the margin of safe fluoride exposure is narrowed in rats that are physiologically compromised by renal dysfunction. The study objective was to determine whether increases in fluoride retention and tissue fluoride levels in rats with surgically induced renal insufficiency result in toxic fluoride effects not ordinarily observed in healthy animals. Uremic and sham-operated control rats received 0 µg/ml, 5 (0.26 mmol/l), 15 (0.79), or 50 µg/ml (2.63 mmol/l) of fluoride in their drinking water for 3 or 6 months. Fluoride retention was monitored, and, following euthanasia, tissue fluoride and biochemical markers of tissue function were analyzed. Selected tissues were saved for histology, and bone marrow cells were harvested for determining the frequency of sister chromatid exchange, a marker of genetic damage. In spite of significantly higher levels of fluoride in the tissues of the animals with renal insufficiency, there were no clinically adverse, fluoride-induced, extraskeletal physiological, biochemical, or genetic effects of chronic exposure to common levels of fluoride in these rats.
High-Energy Shock Waves Alter Cytosolic Calcium Mobilization in Single MDCK Cells
Authors: Jan Chung-Ren , Huang Jong-Khing , Tseng Ching-Jiunn 
Published: April 2003

The damaging effect of shock waves on intracellular calcium homeostasis in renal tubular cells has not been investigated previously. We have examined the effects of shock waves on Madin Darby canine kidney (MDCK) cells by determining the release of two cellular enzymes: glutamate oxalactate transferase (GOT) and lactate dehydrogenase (LDH); and both the basal cytosolic calcium concentration ([Ca<sup>2+</sup>]<sub>i</sub>) and the [Ca<sup>2+</sup>]<sub>i</sub> rises evoked by Ca<sup>2+</sup>-mobilizing agonists after shock wave exposure (SWE). Immediately but transiently after SWE, the release of GOT and LDH increased by 15% and 5-fold, respectively, implicating cell membrane damage; and within 1–7 h after SWE, basal [Ca<sup>2+</sup>]<sub>i</sub> was elevated by 15–141%. In SWE-treated cells, the peak amplitude of the [Ca<sup>2+</sup>]<sub>i</sub> transients evoked by ATP, bradykinin, thapsigargin and 2,5-Di-(t-butyl)-1,4-hydroquinone (BHQ) was slightly altered, and the plateau amplitude was markedly elevated. The ATP and bradykinin receptors, the Ca<sup>2+</sup> pump on the endoplasmic reticulum membrane, and the effector molecules involved in regulating the [Ca<sup>2+</sup>]<sub>i</sub> transients were slightly affected. Shock waves appeared to cause a mild impairment in the mechanisms responsible for the decay of the evoked [Ca<sup>2+</sup>]<sub>i</sub> rises.
End-Stage Renal Disease following Polycythemia vera: In vitro and in vivo Response of Erythroid Progenitors to Erythropoietin and Effects of Sera on Normal Erythropoiesis
Authors: Shih Lee-Yung , Huang Jeng-Yi 
Published: April 2003

We investigated the in vitro erythroid progenitor growth and the effects of sera on normal-marrow CFU-E (colony-forming units – erythroid) growth in 2 patients with renal failure on regular hemodialysis following a prior history of polycythemia vera (PV). PV was diagnosed 3 and 11 years, respectively, before the development of terminal renal failure. One of the patients had entered a spent phase of PV as characterized by diffuse extensive myelofibrosis and anemia; the other also had mild myelofibrosis. The serum erythropoietin (EPO) levels were low or normal on serial measurements by radioimmunoassay. There was no correlation between the hematocrit values and serum EPO levels. EPO-independent erythroid colonies were present in the cultures of bone marrow and peripheral blood cells from both patients after renal failure in the anemic state. With the addition of various concentrations of EPO, the number of erythroid colonies increased as the concentrations of EPO increased which was in accordance with the clinical observation that 1 patient with postpolycythemic myeloid metaplasia partially responded to recombinant human EPO therapy. In the EPO-dependent CFU-E assay, normal-marrow CFU-E numbers supported by 10% of the patient sera were less than those by normal sera. In the absence of EPO in cultures, no erythropoietic activity was found in the patients’ sera. Our study on uremic patients with underlying PV showed that the biologic characteristics of autonomous erythroid progenitor growth for PV persisted during the spent phase and after the development of terminal renal failure with anemia. The erythroid progenitors responded to EPO both in vitro and in vivo. Their sera exhibited an inhibiting effect on the growth of normal-marrow erythroid progenitors.
Correction of Uremic Iron Deficiency Anemia in Hemodialyzed Patients: A Prospective Study
Authors: Fudin Roberto , Jaichenko Jose , Shostak Avshalom , Bennett Michael , Gotloib Lazaro 
Published: April 2003

This prospective study was designed to evaluate the eventual correction of anemia and iron status in 39 iron-deficient uremics starting hemodialysis. Nine patients (control group) had no iron supplementation, 10 had oral ferrous iron, and 20 were treated with intravenous iron gluconate. Follow-up periods were 12 months for the control group and 26 months for patients treated with oral or intravenous iron. No patient was treated with erythropoietin. At zero time, all patients were anemic (Hb <78 g/l) and showed signs of severe iron deficiency, diagnosed on the basis of depleted bone marrow iron stores, reduced hemoglobin iron, and transferrin saturation <21%. The hemoglobin levels, observed in patients of the control and the oral iron groups at the end of the follow-up periods, were not significantly different from those detected at zero time. In contradistinction, patients treated with intravenous iron showed after 26 months of follow-up a significant increase of blood hemoglobin values, reaching a mean value of 126 g/l. So far, this evidence supports both the concept that iron absorption is compromised in chronic uremics and that the parenteral way is the more effective route for iron replacement in this specific group of patients.
Tubular Peptide Hypermetabolism and Urinary Ammonia in Chronic Renal Failure in Man: A Maladaptive Response?
Authors: Rustom R. , Maltby P. , Grime J.S. , Hughes A. , Costigan M. , Shenkin A. , Critchley M. , Bone J.M. 
Published: April 2003

Excessive renal tubular peptide uptake and degradation reflecting hypercatabolism may be a maladaptive response in chronic renal failure (CRF). It may also offer an explanation for the increased ammoniagenesis, per surviving nephron, observed in CRF but as yet unexplained. Neither has been explored in man. We have shown in patients with normal renal function and heavy (>5.0 g/24 h) proteinuria that tubular catabolism of a technetium-labelled peptide marker, aprotinin, and urinary ammonia were increased compared to others with less proteinuria. We now measure tubular kinetics of aprotinin and urinary ammonia in 16 CRF patients with variable proteinuria. Metabolism and turnover of aprotinin and ammonia excretion were increased, corrected for glomerular filtration rate, to levels found in patients with normal function and heavy proteinuria.
Effects of Uremic Plasma on α- and β-Adrenoceptor Subtypes
Authors: Ferchland A. , Rettkowski O. , Pönicke K. , Deuber H.J. , Osten B. , Brodde O.-E. 
Published: April 2003

Responsiveness of adrenergic receptors is decreased in patients on maintenance hemodialysis. In this study we investigated whether uremic plasma might affect adrenergic receptors. For this purpose we determined the effects of uremic plasma obtained from 10 patients on hemodialysis treatment (mean age 61 ± 3 years, dialysis frequency 3 × 4 h/week, duration of treatment 3 ± 1 years) before and at the end of the 4-hour dialysis treatment on binding of radioligands to β<sub>1</sub>- and β<sub>2</sub>- as well as α<sub>1</sub>- and α<sub>2</sub>-adrenoceptors. Plasma from 6 healthy volunteers served as control; the plasmas were studied in three dilutions: undiluted, 1:1 (v/v) and 1:4 (v/v) with saline diluted. Plasma from healthy control did not significantly affect the number of β<sub>1</sub>- and β<sub>2</sub>- or α<sub>1</sub>- and α<sub>2</sub>-adrenoceptors. On the other hand, uremic plasma significantly decreased the number of β<sub>1</sub>- and β<sub>2</sub>-adrenoceptors; this inhibitory effect was also observed when plasma obtained at the end of the 4-hour dialysis treatment was investigated. On the other hand, uremic plasma did not significantly decrease the number of α<sub>1</sub>- and α<sub>2</sub>-adrenoceptors. We conclude that in patients on maintenance hemodialysis, the presence of inhibitory substance(s) in uremic plasma could be – at least partly – responsible for the β-adrenoceptor hyporesponsiveness; the mechanism leading ot α-adrenoceptor hyporesponsiveness, however, remains to be elucidated.
Abnormal Increase of Creatine Kinase Plasma Levels following Muscle Exercise in Nephrotic Patients
Authors: Cupisti Adamasco , Chisari Carmelo , Morelli Ester , Meola Mario , Giannini Elena , Rossi Bruno , Barsotti Giuliano 
Published: April 2003

Nephrotic syndrome is a protein-wasting disorder affecting total body protein metabolism, often leading to reduction of lean body mass and changes of muscle cell composition. The aim of this study was to investigate the susceptibility to muscle cell damage in nephrotic patients following submaximal physical exercise, by detection of the creatine kinase (CK) plasma level changes. Fourteen patients affected by primary nephrotic syndrome, without chronic renal failure, underwent an exercise test on a cycle ergometer for 20 min at a constant speed (60 rpm). In each subject, the work rate (expressed as watts) was established as 70% of the maximum power theoretically calculated on a sex, age, weight and height basis. CK plasma levels (U/l) were determined before and 1, 3, 6 and 24 h after the exercise. Following exercise, CK plasma levels became higher in nephrotics than in normal controls. That is, the amount of CK increments was greater in nephrotics than in controls from the first hour after the end of exertion. These changes, both as absolute values and as percentage of the basal values, correlate positively to daily urinary protein losses; moreover, an inverse relationship was detected with albumin serum levels. However, no correlation was observed between the amount of plasma CK increases and age, body weight, plasma creatinine, plasma cholesterol or hemoglobin levels. These results demonstrate that a greater than normal increase of CK plasma levels occurs in nephrotics following physical exercise, and that this increment correlates with the severity of urinary protein wasting. This suggests an increased susceptibility to muscle injury in nephrotic patients probably related to protein depletion and/or to modifications of muscle cell metabolism. Further studies are needed to define the pathogenesis of our findings.
Effects of Oral Supplementation with Evening Primrose Oil for Six Weeks on Plasma Essential Fatty Acids and Uremic Skin Symptoms in Hemodialysis Patients
Authors: Yoshimoto-Furuie Keiko , Yoshimoto Kazuo , Tanaka Takaomi , Saima Shigeki , Kikuchi Yuka , Shay Janet , Horrobin DavidF. , Echizen Hirotoshi 
Published: April 2003

Abnormalities in plasma composition of essential fatty acids (EFAs) may be associated with the etiology of pruritus and other skin problems in patients undergoing hemodialysis. To study whether an oral supplementation with ω–6 (n–6) EFAs would restore deranged plasma EFAs and ameliorate skin symptoms, 9 and 7 dialysis patients were randomly assigned to receive either γ-linolenic acid (GLA)-rich evening primrose oil (EPO) or linoleic acid (LA) (2 g/day each) for 6 weeks. Plasma concentrations of EFA were analyzed by gas chromatography and uremic skin symptoms were assessed for dryness, pruritus and erythema by questionnaire and visual inspection in a double-blind manner. The patients given EPO exhibited a significant (p < 0.05) increase in plasma dihomo-γ-linolenic acid (a precursor of anti-inflammatory prostaglandin E<sub>1</sub>) with no concomitant change in plasma arachidonic acid (a precursor of pro-inflammatory prostaglandin E<sub>2</sub> and leukotriene B<sub>4</sub>). In contrast, those given LA exhibited a significant (p < 0.05) increase in LA but not in any other n–6 EFAs, whereas they exhibited a significant (p < 0.05) decrease in plasma docosahexaenoic acid. The patients given EPO showed a significant (p < 0.05) improvement in the skin scores for the three different uremic skin symptoms over the baseline values and a trend toward a greater improvement (0.05 < p < 0.1) in pruritus scores than those given LA. Results indicate that GLA-rich EPO would be a more favorable supplemental source than LA in terms of shifting eicosanoid metabolism toward a less inflammation status through modifying plasma concentrations of their precursor n–6 EFAs. Further studies are required to confirm the efficacy and safety of EPO therapy for the treatment of uremic pruritus.
Relationship between Urinary Albumin Excretion and Glomerular Filtration Rate in Normotensive, Nonproteinuric Patients with Type 2 Diabetes mellitus
Authors: Taniwaki Hiromichi , Ishimura Eiji , Emoto Masanori , Kawagishi Takahiko , Matsumoto Naoki , Shoji Tetsuo , Okamura Terue , Inaba Masaaki , Nishizawa Yoshiki 
Published: April 2003

<i>Background/Aim:</i> In patients with type 2 diabetes mellitus, the relationship between glomerular filtration rate (GFR) and urinary albumin excretion remains an unresolved issue. In order to investigate the early renal function abnormalities, GFR and urinary albumin excretion were assessed, and their relationship was examined in normotensive patients with type 2 diabetes mellitus. <i>Methods:</i> In a cross-sectional study of 85 nonhypertensive Japanese patients with type 2 diabetes mellitus not showing overt proteinuria, the GFR was measured using <sup>99m</sup>Tc-diethylenetriamine pentaacetate renography. Fifty-one diabetic patients lacked microalbuminuria (albumin excretion <30 mg/day), while 34 patients showed microalbuminuria (between 30 and 300 mg/day). Fifteen healthy subjects served as controls. <i>Results:</i> The three groups were well matched with regard to gender, age, and body mass index. The GFR in microalbuminuric patients (134 ± 23 ml/min/1.48 m<sup>2</sup>) was significantly higher than in patients without microalbuminuria (108 ± 21 ml/min/1.48 m<sup>2</sup>) and in controls (109 ± 18 ml/min/1.48 m<sup>2</sup>; p < 0.0001). In type 2 diabetic patients, the GFR positively correlated with the logarithmically transformed urinary albumin excretion. Multiple regression analysis showed that the urinary albumin excretion was significantly and independently affected by GFR (β = 0.548), duration of diabetes (β = 0.297), and systolic blood pressure (β = 0.232; R<sup>2</sup> = 0.409; p < 0.0001). <i>Conclusion:</i> It is suggested that one of the mechanisms underlying increased urinary albumin excretion in early nephropathy in normotensive type 2 diabetes is glomerular hyperfiltration.