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K Siamopoulos
Nephrology Dialysis Transplantation 02/2001; 16 Suppl 6:46-7. · 3.40 Impact Factor
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E Briasoulis,
I Judson,
N Pavlidis,
P Beale,
J Wanders,
Y Groot,
G Veerman,
M Schuessler,
G Niebch, K Siamopoulos,
E Tzamakou,
D Rammou,
L Wolf,
R Walker,
A Hanauske
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ABSTRACT: To determine the maximum-tolerated dose (MTD), the principal toxicities, and the pharmacokinetics of 6-hour infusion of glufosfamide (beta-D-glucosylisophosphoramide mustard; D-19575), a novel alkylating agent with the potential to target the glucose transporter system.
Twenty-one patients (10 women and 11 men; median age, 56 years) with refractory solid tumors were treated with doses ranging from 800 to 6,000 mg/m(2). Glufosfamide was administered every 3 weeks as a two-step (fast/slow) intravenous infusion over a 6-hour period. All patients underwent pharmacokinetic sampling at the first course.
The MTD was 6,000 mg/m(2). At this dose, two of six patients developed a reversible, dose-limiting renal tubular acidosis and a slight increase in serum creatinine the week after the second and third courses of treatment, respectively, whereas three of six patients experienced short-lived grade 4 neutropenia/leukopenia. Other side effects were generally mild. Pharmacokinetics indicated linearity of area under the time-versus-concentration curve against dose over the dose range studied and a short elimination half-life. There was clear evidence of antitumor activity, with a long-lasting complete response of an advanced pancreatic adenocarcinoma and minor tumor shrinkage of two refractory colon carcinomas and one heavily pretreated breast cancer.
The principal toxicity of 6-hour infusion of glufosfamide is reversible renal tubular acidosis, the MTD is 6,000 mg/m(2), and the recommended phase II dose is 4, 500 mg/m(2). Close monitoring of serum potassium and creatinine levels is suggested for patients receiving glufosfamide for early detection of possible renal toxicity. Evidence of antitumor activity in resistant carcinomas warrants further clinical exploration of glufosfamide in phase II studies.
Journal of Clinical Oncology 11/2000; 18(20):3535-44. · 18.37 Impact Factor
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ABSTRACT: A number of adverse metabolic effects are associated with indapamide administration, including an increase in serum uric acid levels. It has been reported that losartan can significantly decrease serum uric acid levels. However, there are no data on the effects of combination therapy of losartan with indapamide on uric acid metabolism.
We studied 20 hypertensive patients in whom serum metabolic parameters, including uric acid levels in serum and urine, were studied before and after eight weeks of indapamide administration (2.5 mg once daily) as well as eight weeks after combination treatment with indapamide (2.5 mg once daily)and losartan (50 mg/day).
Indapamide evoked a significant decrease in systolic and diastolic blood pressure from a mean value of 157 +/- 12 mmHg/96 +/- 10 mmHg to a mean value of 139 +/- 14 mmHg/92 +/- 5 mmHg (p<0.01 for both comparisons). However, a significant increase in serum uric acid levels was noticed after indapamide administration (from a mean value of 4.9 +/- 1.6 mg/dl to a mean value of 5.9 +/- 1.2 mg/dl, p<0.01), associated with a decrease in the fractional excretion of uric acid(from a mean value of 9 +/- 5% to a mean value of 7 +/- 5.5%, p<0.05). The addition of losartan caused a further decrease in blood pressure from a mean value of 139 +/- 14 mmHg/92 +/- 5 mmHg to a mean value of 120 +/- 15 mmHg/84 +/- 4 mmHg (p<0.01 for both comparisons). This was followed by a significant decrease in serum uric acid levels to 5 +/- 1.1 mg/dl(p<0.01) due to a substantial increase in fractional urate excretion (from 7 +/- 5.5 to 8.7 +/- 6%, p<0.05).
The addition of losartan could offset the hyperuricaemic effect of indapamide administration.
Journal of Renin-Angiotensin-Aldosterone System 09/2000; 1(3):289-91. · 2.44 Impact Factor
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QJM: monthly journal of the Association of Physicians 06/2000; 93(5):318-9. · 2.33 Impact Factor
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Clinical Chemistry and Laboratory Medicine 03/1999; 37(2):165. · 2.15 Impact Factor
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ABSTRACT: We report a case of a 39-year-old man with lambda-light-chain multiple myeloma, nephrotic syndrome due to lambda-light-chain deposition disease in kidneys and amyloidosis in other tissues. The patient was treated with melphalan and prednisone for 1 year. After that, he was administered interferon-alpha2b (IFN-alpha2b; 3 MU, 3 times a week) as maintenance therapy for 2 years. At present, 5 years and 6 months after the initial diagnosis, the patient receives IFN-alpha2b (3 MU, twice a week) and remains in complete haematological remission.
Acta Haematologica 02/1999; 101(4):202-5. · 1.35 Impact Factor
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ABSTRACT: Hyponatremia commonly complicates the clinical course of patients with congestive heart failure (CHF) and seems to be an ominous prognostic factor. Angiotensin-converting enzyme (ACE) inhibitors improve the symptomatology of CHF patients. Moreover, it has been reported that these drugs can raise serum sodium in hyponatremic patients. The aim of this prospective work was to study the mechanisms involved in the correction of hyponatremia in 6 patients aged 52-69 years with CHF and hyponatremia (serum sodium 125-128 mmol/l) who were receiving digitalis and furosemide. In these patients, captopril was introduced in progressively increasing doses. The drug induced significant clinical improvement. Additionally, a statistically significant increase in serum sodium was observed which was correlated to a rise in the diluting ability of the kidney (increase in CeH2O). A slight increase in creatinine clearance was also found, which could have contributed to the improvement in hyponatremia. Therefore, we conclude that ACE inhibitors can improve hyponatremia in CHF patients by increasing the urinary diluting ability.
Cardiology 02/1995; 86(6):477-80. · 1.71 Impact Factor
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ABSTRACT: To evaluate the effect of an acute oral protein load (OPL) on urinary albumin excretion (UAE) in uninephrectomized subjects with a negative Albustix test, in relation to the time since nephrectomy, the UAE was determined by a double-antibody 125I radioimmunoassay in 3-hour urine collections before and after 150 g OPL under conditions of moderate physical activity in 18 subjects who underwent unilateral nephrectomy more than 10 years (346.5 +/- 178.60 months) before evaluation and had a mean basal creatinine clearance (CCr) of 45.3 +/- 14 ml/min (group 1), in 21 subjects who underwent unilateral nephrectomy less than 10 years (31.5 +/- 28 months) before evaluation and had a mean basal CCr of 76.0 +/- 22 ml/min (group 2), and in 16 normal volunteers (controls) with a mean basal CCr of 103.1 +/- 12 ml/min. The UAE was higher in group 1 as compared with either group 2 or controls at both basal state (90.8 +/- 65, 19.6 +/- 17, and 11.0 +/- 5 micrograms/min/100 CCr for groups 1 and 2 and controls, respectively; p < 0.001) and after OPL (92.0 +/- 65, 43.6 +/- 24, and 12.0 +/- 5 micrograms/min/100 CCr for groups 1 and 2 and controls, respectively; p < 0.001). However, the increase in UAE following OPL was significant (p < 0.001) only in group 2 patients. In all patients, the basal UAE was negatively correlated with basal CCr (r = 0.63; p < 0.001) and positively correlated with the time since nephrectomy (r = 0.73; p < 0.001) and with both systolic (r = 0.57; p < 0.001) and diastolic blood pressures (r = 0.69; p < 0.001). CCr calculated using 3-hour urine collections increased more in controls (11.2 +/- 44.2%) than in patient groups 1 (1.6 +/- 0.89) and 2 (7.7 +/- 3.7%; p < 0.001). Basal CCr calculated using 24-hour urine collections the day before the test was negatively correlated with the time since nephrectomy in group 1 (r = -0.69; p < 0.001) and positively correlated with the time since nephrectomy in group 2 (r = 0.89; p < 0.001). Multiple regression analysis revealed that the relationship between CCr and duration of uninephric state was independent of age or systolic and diastolic blood pressures in both patient groups. These results suggest that UAE increase significantly after an OPL in subjects who have been nephrectomized less than 10 years before the study and have basal CCr values higher than 50% of normal.(ABSTRACT TRUNCATED AT 250 WORDS)
Nephron 01/1994; 68(2):169-79. · 13.26 Impact Factor
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ABSTRACT: Phosphatidylcholine (PC), which has successfully been used in the past to increase ultrafiltration in continuous ambulatory peritoneal dialysis (CAPD) patients, has recently been found to prevent experimental adhesion formation after intraperitoneal irrigation with warm saline. The aim of this study was to determine the most effective route(s) of PC administration in the aforementioned model. Eighty Wistar rats underwent laparotomy and intraperitoneal irrigation with saline at 40 degrees C, which in 20 rats was followed by closure of the abdomen (control group, GC). In another 20 rats PC was given per os before and after irrigation (per os PC group, GOPC). In the third group PC was diluted in the irrigation fluid (intraperitoneal PC group, GIPC), and in the last group PC was given per os and intraperitoneally (combined PC group, GCPC). Assessment of adhesions was performed 2 weeks after the irrigation. Adhesions were found in 12 rats in the GC, 5 rats in the GOPC (p = 0.05, Fisher's test), 17 rats in the GIPC, and 3 rats in the GCPC (p = 0.007, Fisher's test). The difference between GOPC and GCPC was not statistically significant. The decreased adhesion formation after PC administration combined with the increased ultrafiltration may be of considerable importance in CAPD patients.
Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis 02/1993; 13 Suppl 2:S77-8. · 2.10 Impact Factor
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Basic life sciences 02/1990; 55:89-93.
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ABSTRACT: Epidemiological investigations were conducted following an outbreak of hemorrhagic fever with renal syndrome (HFRS) which occurred in the state of Epirus, northwestern Greece, in July and August 1983. A total of 8 patients were hospitalized during the outbreak; 3 were severely ill and 1 died. A serosurvey made in May 1984 sampled 184 of the approximately 400 residents of the village of Tsepelovo, where 4 patients resided, and found 12 (6.5%) persons, including convalescent sera from 4 patients, with antihantaviral antibody by immunofluorescent antibody (IFA) tests. Small mammal collections found house rats common in the village, but none exhibited anti-hantaviral antibody. Collections in nearby fields and mountains found Apodemus flavicollis rodents common, and 2 (6%) of 33 captured had high IFA anti-hantavirus antibody. Virus isolation attempts from rodent tissues were unsuccessful. Testing of convalescent patients' sera by IFA and plaque reduction neutralization tests indicated that the etiological agent was neither Puumala virus nor Seoul virus, but appears to be a strain of Hantaan virus or perhaps a new virus. The rodent host of this virus may be A. flavicollis, and the distribution of this species corresponds with previously reported cases of severe HFRS described elsewhere in central Europe.
The American journal of tropical medicine and hygiene 06/1986; 35(3):654-9. · 2.59 Impact Factor
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ABSTRACT: An outbreak of eight cases of haemorrhagic fever with renal syndrome in North-West Greece is presented. The major clinical manifestation was fever and all patients subsequently developed decreased renal function and proteinuria. The disease was diagnosed by rising antibody titers to the Hantaan virus.
European journal of clinical microbiology 05/1985; 4(2):132-4. · 2.61 Impact Factor
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ABSTRACT: It has recently been suggested that increased lipoprotein (a) levels are an independent risk factor for coronary heart disease. It has also been reported that tamoxifen can induce changes in blood lipid values. In this prospective study we investigated the long term effects tamoxifen on the lipid profile, focusing on lipoprotein (a) levels. Thirty-eight postmenopausal women with breast cancer treated with tamoxifen at a dose of 20 mg daily were studied. The mean age was 61 years. Serum lipoprotein (a) levels and lipid parameters (total cholesterol, high and low density lipoprotein cholesterol, triglycerides, apolipoprotein A-I and B) were measured after an overnight fast on the 1, 3, 6 and 9 month of tamoxifen treatment. A progressive fall in median lipoprotein(a) levels from 8 mg/dl to 3 mg/dl (p < 0.001) was observed. In addition, a significant decrease in the total and low density lipoprotein cholesterol and in apolipoprotein B, as well as an increase in apolipoprotein A-l were also noticed. It is concluded that our data on serum lipoprotein(a) levels agree with the beneficial anti-atherogenic effects of tamoxifen administration on lipoproteins.
Anticancer research 16(5A):2725-8. · 1.73 Impact Factor
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