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Biomedical subjects

T H Ittel

Publications and source records attributed to T H Ittel.

At least 19 recordsLinked to original sources
PubMed2003

Pegylated asparaginase in combination with high-dose methotrexate for consolidation in adult acute lymphoblastic leukaemia in first remission: a pilot study.

The German Multicentre acute lymphoblastic leukaemia (ALL) study group (GMALL) performed a pilot study using pegylated asparaginase (PEG-ASP) in combination with high-dose methotrexate as consolidation therapy in the 05/93 protocol. The aim of the study was an intra-individual comparison of two different doses of PEG-ASP in 26 patients, with regard to the depletion of asparagine in serum and toxicity. 'Pharmacokinetic' monitoring was performed to evaluate the effect of an intra-individual dose escalation of PEG-ASP from 500 to 1000 U/m2 intravenously in successive doses. Serum asparaginase activity was targeted at > or =100 U/l for 1 week and > or =50 U/l for 10 d. The second course of PEG-ASP was administered to 23 patients. Due to hypersensitivity reactions in five patients, only 18 patients were evaluable for pharmacokinetic monitoring. With respect to the PEG-ASP activity, an effective depletion of asparagine could be postulated in the majority of patients during 10 d after the first administration. The effect of an intraindividual dose escalation form 500 to 1000 U/m2 was evaluable in 17 of 22 patients. An increment in peak PEG-ASP activity >70% was observed in 65% of the patients. PEG-ASP was well tolerated. Despite the long half-life of PEG-ASP, neither pancreatic nor central nervous toxicities occurred among the 26 adult patients treated in this pilot study.

Adolescent↗
PubMed2003

[Secondary and primary prophylaxis of gastropathy associated with nonsteroidal antiinflammatory drugs or low-dose-aspirin: a review based on four clinical scenarios].

Based on current references four clinical scenarios were discussed and different management strategies were compared for secondary and primary prophylaxis of ulcer or peptic ulcer bleeding under continuous therapy with non-steroidal antiinflammatory drugs (NSAID) or low-dose-aspirin, for H.pylori-positive and H.pylori-negative patients. Used as secondary prophylaxis eradication alone is insufficient in preventing recurrent peptic ulcer or recurrent ulcer bleeding for H.pylori-positive patients who continue to take unselective NSAIDs. Maintenance therapy with PPIs or switching from nonselective NSAID to COX-2-inhibitors is required after eradication of H.pylori or primary H.pylori-negative patients. Further evaluation is needed of what kind of secondary prophylaxis - maintenance therapy with PPI or switching to COX-2-inhibitor - is more (cost-)effective. It is sufficient to use eradication of H.pylori alone as secondary prophylaxis in preventing recurrent peptic ulcer or recurrent ulcer bleeding for H.pylori-positive patients, who continue to take low-dose-aspirin. Maintenance therapy with PPI is not generally required. However it can be considered for patients with increased risk for gastrointestinal complications (previous history of peptic ulcer, age over 65 years, concomitant use of corticosteroids, anticoagulants or individual NSAID with higher risk for gastrointestinal complications, serious cardiovascular disease). Switching from low-dose-aspirin to clopidogrel is not required. Used as primary prophylaxis in preventing peptic ulcer or ulcer bleeding before starting long-term therapy with NSAIDs, COX-2-inhibitors or unselective NSAIDs concomitant with PPIs are recommended for patients with increased risk for gastrointestinal complications. Patients starting long-term therapy with unselective NSAIDs should be screened for H.pylori and eradicated. There are no valid data supporting screening for H.pylori and eradication for patients starting long-term therapy with low-dose-aspirin. Further studies are needed to evaluate a possible benefit for patients with increased risk for gastrointestinal complications.

Aged↗
PubMed2002

[Day-night variability of the prehospital phase of acute myocardial infarct].

While a circadian rhythm in the onset of acute myocardial infarction (AMI) is well established, little is known about the variability of prehospital delay and decision processes. Seven hundred and thirty-nine consecutive AMI patients (median age 65.3 years; 30.2% women) with a median decision time of 60 min and a total prehospital delay of 180 min were studied. In 30.9% of patients onset of AMI symptoms was at night (10.00 p.m.-06.00 a.m.). At night patient decision time was significantly longer than during daytime (120 vs 45 min, difference 75 min; p < 0.001), total prehospital delay was prolonged accordingly (240 vs 170 min, difference 70 min; p < 0.001). The relative risk (RR; 95% confidence interval, CI) for a late decision (> 1 h) to seek medical care at night was significantly increased in females (RR 1.96; CI 1.07-3.61, p = 0.028), non-smokers (RR 2.49; CI 1.42-4.39, p = 0.001) and patients with radiation of anginal pain (RR 2.34; CI 1.32-4.15; p = 0.003). Of all patients with a late decision to seek medical care at night, 95.6% belonged to one of these groups. These variables were not significant for early or late decisions during daytime. Decision processes of AMI patients may be different during daytime and at night. In conclusion, in AMI patients, decision time to seek medical help is prolonged at night. Simple clinical variables (female sex, non-smokers, radiation of anginal pain) identify patients at high risk for a late decision at night. This information should be included into public and individualized education campaigns.

Aged↗
PubMed2002

Emotional attitudes toward symptoms and inadequate coping strategies are major determinants of patient delay in acute myocardial infarction.

BACKGROUND: Early reperfusion treatment in acute myocardial infarction (AMI) preserves ventricular function and saves lives. After onset of AMI symptoms, patients often delay for hours until the decision to seek medical help. AIM: Of the MI-heart (Myocardial Infarction--HElp seeking And ReacTions) study was to identify factors determining patient decision delay. METHODS: 739 consecutive patients with confirmed AMI (median age 65.3 years, 30.2% females) were studied after transfer from the intensive care unit. A standardized interview covered AMI symptoms, attitudes toward symptoms, coping strategies, and clinical and sociodemographic variables. RESULTS: Of patients, 93.3% knew an AMI could be deadly. 43.9% of the patients who suspected an AMI, and knew it could be deadly, decided late (> 1 hour) to seek medical help. In univariate analyses, attitudes toward symptoms and coping strategies had the highest impact on a late decision. Stepwise logistic regression identified the following independent contributors to a late decision to seek medical help (relative risk, 95% confidence interval): wanting to wait and see (3.53; 2.32-5.39), not taking symptoms seriously (2.47; 1.64-3.72), not wanting to bother anybody (2.14; 1.29-3.57), symptoms improving at first (2.33; 1.52-3.56), asking others for advice (0.46; 0.30-0.71), taking pain medication (2.01; 1.01-4.03), age > 65 years (1.69; 1.17-2.44), very strong intensity of angina (0.60; 0.42-0.87). CONCLUSIONS: Emotional attitudes to AMI symptoms and inadequate coping strategies are the major determinants of patient decision delay. They should be considered as a key factor in patient and public education. Modification of these emotional factors might best be achieved by an individualized approach.

Adaptation, Psychological↗
PubMed2001

[Bradycardia despite hyperthyroidism].

Hyperthyroidism is usually associated with tachycardia, hypothyroidism with bradycardia. After observing clinically inapparent hyperthyroidism in patients requiring pacemaker implantation, we studied the occurrence of hyperthyroidism in patients receiving a first permanent pacemaker. Of 237 patients (age 71.4 +/- 8.9 years; 54.9% females), 16 (6.75%) had subclinical (TSH < 0.1 mE/l and fT3 < or = 9.0 pmol/l) and 4 (1.69%) overt hyperthyroidism (TSH < 0.1 mE/l and fT3 > 9.0 pmol/l). Prevalence of hyperthyroidism was similar to that in the general population. Compared to euthyroid patients, in the patients with subclinical or overt hyperthyroidism there were significantly more females (n = 16) than males (n = 4; p = 0.018). Hyperthyroid patients were older (75.0 +/- 9.6 vs. 70.7 +/- 8.9 years; p = 0.015). At follow-up, all patients had a relevant proportion of pacemacer-induced beats. Clinical signs of hyperthyroidism or cardiac symptoms were not different between groups. In conclusion, bradycardia does not exclude the presence of hyperthyroidism. Temporary pacing is recommended in thyreotoxicosis with bradycardia. In contrast, primary implantation of a permanent pacemaker appears to be adequate in patients with bradycardia, cardiovascular disease and an additional diagnosis of hyperthyroidism.

Age Factors↗
PubMed2000

Intensive chemotherapy with idarubicin, ara-C, etoposide, and m-AMSA followed by immunotherapy with interleukin-2 for myelodysplastic syndromes and high-risk Acute Myeloid Leukemia (AML).

Intensive chemotherapy followed by treatment with interleukin-2 (IL-2) was evaluated in a prospective, randomized, multicenter trial including 18 patients with refractory anemia with excess of blasts in transformation (RAEB-T), 86 patients with acute myeloid leukemia (AML) evolving from myelodysplastic syndromes, and six patients with secondary AML after previous chemotherapy. Median age was 58 years (range: 18-76 years). Forty-nine patients (45%) achieved a complete remission (CR) after two induction cycles with idarubicin, ara-C, and etoposide, 52% of them aged </=60 years and 35% aged >60 years (p=0.06). After two consolidation courses, patients were randomized to four cycles of either high- or low-dose IL-2. Patients aged up to 55 years with an HLA-identical sibling donor were eligible for allogeneic bone marrow transplantation. The median relapse-free survival was 12.5 months, with a probability of ongoing CR at 6.5 years of 19%. Overall survival of all patients was 8 months, and 21 months for the CR patients. Median survival was significantly longer among patients aged </=60 years than among the older patients (16 vs 6 months, p<0.001). Median duration of survival and relapse-free survival were not statistically different in the two IL-2 treatment arms.

Acute Disease↗
PubMed2000

Out-of-hospital cardiac arrest in north-east Germany: increased resuscitation efforts and improved survival.

In the years after 1989 major political and socioeconomic changes have taken place in East Germany. In parallel, emergency medical services (EMS) were restructured according to western standards. In Stralsund the EMS was restructured from a single to a two tier system with implementation of a second ambulance base in 1990. The number of household telephone extensions more than doubled. To analyze the effects of these changes, patients receiving advanced life support (ALS) for out-of-hospital cardiac arrest of cardiac origin (OHCA) between 1984 and 1988, and from 1991 to 1997 were studied. Adjusted per 100,000 inhabitants, the number of OHCA patients receiving ALS increased from 11 per year before 1989 to 52 per year after 1990 (P < 0.01). Survival without relevant neurologic defects was achieved in 3.7% (2/53) of patients before 1989 and in 8.1% (22/273) after 1990. Response time of the ALS unit shortened from 11.0 +/- 1.4 to 9.0 +/- 0.4 min (n.s.), while response time of any EMS shortened from 11.0 +/- 1.4 to 6.1 +/- 0.3 min (P < 0.005). Adjusted for observation period and population served, there was a 10-fold increase in the number of resuscitations attempted at home and an 8-fold increase in the absolute number of OHCA survivors without relevant neurological defects. In parallel to socioeconomic changes, the restructuring of the EMS in Stralsund and the rapid expansion of the telephone network led to a significant increase in the number of patients successfully resuscitated from OHCA. If the present results can be transferred to other former socialist countries of East and Middle Europe, they may have important implications for the EMS in these regions.

Emergency Medical Services↗
PubMed1999

Regulation of beta2-microglobulin expression in different human cell lines by proinflammatory cytokines.

BACKGROUND: Proinflammatory monocytic cytokines such as interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF-alpha) and IL-6 have been incriminated in the pathogenesis of elevated beta2-microglobulin (beta2M) serum concentrations in patients undergoing haemodialysis with so-called bioincompatible dialyser membranes. However, neither the source of the elevated serum beta2M nor the precise role of monocytic cytokines in the expression of the beta2M gene have been elucidated conclusively. The aim of the current study was to evaluate whether monocytic cytokines, and in particular IL-6, are regulators of beta2M gene expression in human hepatoma cells, T-lymphocytes and monocytes. METHODS: HepG2 and HuH7 human hepatoma cells, Jurkat T-cells, monocytic MonoMac6 cells, primary human monocytes and synoviocytes were stimulated with IL-1beta, IL-6, interferon-alpha (IFN-alpha), IFN-gamma or conditioned media from lipopolysaccharide (LPS)-treated monocytes. Expression of beta2M mRNA was analysed by Northern blotting, beta2M protein synthesis was determined by metabolic labelling and immunoprecipitation, and beta2M secretion was measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: In all cell types tested, IFN-gamma and, to a lesser extent, IFN-alpha stimulated gene expression of beta2M resulting in an increased synthesis and secretion of beta2M protein. Neither IL-1beta and IL-6 nor supernatants from LPS-treated monocytes were capable of inducing beta2M gene expression, with the exception of a small increase in HuH7 hepatoma cells upon IL-1beta treatment. CONCLUSIONS: The present study provides evidence that interferons are important regulators of beta2M expression. It also shows that proinflammatory monocytic cytokines do not modulate directly the expression of beta2M in cells of hepatic, monocytic and T-lymphocytic origin. Whether they influence beta2M synthesis and secretion indirectly by modulating interferon synthesis needs to be elucidated.

Cell Line↗
PubMed1998

Simulation of a pheochromocytoma--Munchausen syndrome.

A 46-year old female nursing sister was admitted to three different hospitals because of blood pressure crises of 300/150 mmHg which occurred up to six times a day. The rises in blood pressure were accompanied by headache, tachycardia and outbreaks of sweating. Raised catecholamine concentrations were repeatedly measured in the 24-hour urine and in the blood. The diagnosis of pheochromocytoma could therefore be regarded as confirmed. The investigations to establish the localization (including MIBG scintigrams carried out several times) showed negative results. Octreotide scintigraphy finally revealed a raised concentration of nuclides in the right adrenals. Selective venous blood samples showed markedly raised concentrations of adrenaline and noradrenaline in all regions investigated. After removing the right adrenal, which was of normal histological appearance, there was an improvement for six months. Afterwards, up to six blood pressure crises per day were observed once more. Fresh determination of catecholamines at various levels demonstrated the highest concentrations in the left iliac vein. It was then shown that the patient injected catecholamines intravaginally even during the angiographic investigation. A search of the patient s room revealed several ampoules containing noradrenaline and adrenaline as well as syringes and needles. - This case shows that in clinical pictures with typical clinical symptoms and negative results of repeated investigations a factitious disorder must be considered in terms of differential diagnosis especially when female patients with medical knowledge who have ready access to drugs are involved with a history comprising several stays in hospital which have not produced any clarification of their condition.

Adrenal Gland Neoplasms↗
PubMed1998

Retinal capillary density in patients with arterial hypertension: 2-year follow-up.

BACKGROUND: Arterial hypertension is known to be an important risk factor for cerebral and cardiovascular disease. Previous studies have demonstrated a decrease of capillary density in the perifoveal network in tandem with decreased capillary flow velocity in patients with essential hypertension. In a prospective study we quantified the retinal microcirculation in order to evaluate the time course of changes in the perifoveal network. METHODS: Thirty-three patients with essential hypertension (mean age 45 +/- 14 years) underwent video-fluorescein angiographic studies at baseline and at 2 years 28 +/- 6 months) thereafter. The angiograms were obtained with a scanning laser ophthalmoscope and were digitally recorded. By means of digital image analysis we quantified off-line the mean area of perifoveal intercapillary areas (PIA) and the mean capillary flow velocity. RESULTS: At baseline, the patients with hypertension showed significantly increased PIA and a significantly decreased capillary flow velocity compared with reference values. During the follow-up period the capillary flow velocity decreased further significantly, whereas the PIA showed no significant change. CONCLUSIONS: The continuous decrease of capillary flow velocity demonstrates a progression of altered microcirculation in patients with essential hypertension whose blood pressure was believed to be well controlled. Further studies with this technique may be useful to determine the influence of antihypertensive therapy and may help to identify patients at risk for cerebrovascular events.

Blood Flow Velocity↗
PubMed1998

Remission of IgA nephropathy following treatment of cytomegalovirus infection with ganciclovir.

Following the detection of cytomegalovirus antigen in mesangial cells of some patients with IgA nephropathy, an important role of human cytomegalovirus in the pathogenesis of IgA nephropathy has been discussed. We studied a case of IgA nephropathy with rapid deterioration of renal function associated with cytomegalovirus infection. Following an infection of the upper respiratory tract, a 57-year-old woman developed with hematuria and acute renal failure. The histological diagnosis of IgA nephropathy was established and renal function transiently improved during immunosuppressive therapy. However, the ensuing clinical course was complicated by severe bleeding from intestinal ulcera, thrombocytopenia, pneumonia and relapse of renal failure. The histological investigation of colonic mucosa showed characteristic "owl's eye" cells leading to the diagnosis of cytomegalovirus disease as the cause of intestinal bleeding. Immunosuppression was stopped and treatment with ganciclovir started. Pneumonia as well as intestinal bleeding disappeared and, of particular note, renal function improved considerably. Following discontinuation of antiviral therapy CMV-disease reoccurred and renal function deteriorated again. The patient was restarted on ganciclovir therapy and, again, serum creatinine fell quickly. This impressive and reproducible clinical improvement of renal insufficiency under antiviral therapy with ganciclovir provides some evidence for an important role of cytomegalovirus in the pathogenesis of this case of IgA nephropathy.

Antiviral Agents↗
PubMed1997

Ultrasensitive analysis of the intestinal absorption and compartmentalization of aluminium in uraemic rats: a 26Al tracer study employing accelerator mass spectrometry.

BACKGROUND: Developments in accelerator mass spectrometry (AMS) now permit the determination of femtogram amounts of 26Al in blood and in various tissues with good precision and free of external contamination. METHODS: In the present study we used trace quantities of 26Al to investigate the intestinal absorption and compartmentalization of aluminium in rats with renal failure (Nx, 5/6 nephrectomy) and in pair-fed controls (C). Single oral doses of 20 ng 26Al were administered to six animals in each group and, subsequently, 24-h post-load 26Al was analysed in serum, urine, bone, liver, and spleen by means of AMS. RESULTS: Serum concentrations of 26Al were significantly lower in uraemic rats compared to controls, whereas urinary excretion was comparable (Nx, 7.11 +/- 5.78 pg/day vs C, 9.46 +/- 6.10 pg/day), suggesting a higher fraction of ultrafiltrable serum 26Al in uraemia. The target tissues of cellular transferrin-mediated 26Al uptake, liver and spleen, tended to show a larger degree of aluminium accumulation in controls (0.26 +/- 0.31 pg/g vs Nx, 0.14 +/- 0.10 pg/g and 0.37 +/- 0.27 pg/g vs Nx, 0.25 +/- 0.27 pg/g respectively). In contrast, in bone, a site of extracellular aluminium deposition, 26Al concentrations were more elevated in uraemia (1.22 +/- 0.59 pg/g vs C: 0.68 +/- 0.30 pg/g). Estimated total 26Al accumulation in all measured target tissues was significantly higher in uraemic rats (28.15 +/- 9.90 pg vs C: 17.03 +/- 7.03 pg) and total recovery of 26Al from tissue and urine was 26.58 +/- 6.74 pg in controls and 35.75 +/- 7.03 pg in uraemic animals, suggesting a fractional absorption of 0.133% and 0.175% respectively. CONCLUSIONS: Our data suggest that fractional absorption from a dietary level dose of 26Al is about 0.13%. Compartmentalization occurs in transferrin-dependent target tissues such as liver and spleen; however, in quantitative terms extracellular deposition in bone is more important. Uraemia has a significant effect on the intestinal absorption and compartmentalization of aluminium. It enhances fractional absorption and increases subsequent extracellular deposition of aluminium in bone. However, at the same time uraemia does not increase transferrin-dependent cellular accumulation of aluminium in liver and spleen.

Aluminum↗
PubMed1996

Improved outcome in adult B-cell acute lymphoblastic leukemia.

A total of 68 adult patients with B-cell acute lymphoblastic leukemia (B-ALL) were treated in three consecutive adult multicenter ALL studies. The diagnosis of B-ALL was confirmed by L3 morphology and/or by surface immunoglobulin (Slg) expression with > 25% blast cell infiltration in the bone marrow (BM). They were characterized by male predominance (78%) and a median age of 34 years (15 to 65 y) with only 9% adolescents (15 to 20 y), but 28% elderly patients (50 to 65 y). The patients received either a conventional (N = 9) ALL treatment regimen (ALL study 01/81) or protocols adapted from childhood B-ALL with six short, intensive 5-day cycles, alternately A and B. In study B-NHL83 (N = 24) cycle A consisted of fractionated doses of cyclophosphamide 200 mg/m2 for 5 days, intermediate-dose methotrexate (IdM) 500 mg/m2 (24 hours), in addition to cytarabine (AraC), teniposide (VM26) and prednisone. Cycle B was similar except that AraC and VM26 were replaced by doxorubicin. Major changes in study B-NHL86 (N = 35) were replacement of cyclophosphamide by ifosphamide 800 mg/m2 for 5 days, an increase of IdM to high-dose, 1,500 mg/m2 (HdM) and the addition of vincristine. A cytoreductive pretreatment with cyclophosphamide 200 mg/m2, and prednisone 60 mg/m2, each for 5 days was recommended in study B-NHL83 for patients with high white blood cell (WBC) count (> 2,500/m2) or large tumor burden and was obligatory for all patients in study B-NHL86. Central nervous system (CNS) prophylaxis/treatment consisted of intrathecal methotrexate (MTX) therapy, later extended to the triple combination of MTX, AraC, and dexamethasone, and a CNS irradiation (24 Gy) after the second cycle. Compared with the ALL 01/81 study where all the patients died, results obtained with the pediatric protocols B-NHL83 and B-NHL86 were greatly improved. The complete remission (CR) rates increased from 44% to 63% and 74%, the probability of leukemia free survival (LFS) from 0% to 50% and 71% (P = .04), and the overall survival rates from 0% to 49% and 51% (P = .001). Toxicity, mostly hematotoxicity and mucositis, was severe but manageable. In both studies B-NHL83 and B-NHL86, almost all relapses occurred within 1 year. The time to relapse was different for BM, 92 days, and for isolated CNS and combined BM and CNS relapses, 190 days (P = .08). The overall CNS relapses changed from 50% to 57% and 17%, most probably attributable to the high-dose MTX and the triple intrathecal therapy. LFS in studies B-NHL83 and B-NHL86 was significantly influenced by the initial WBC count < or > 50,000/microL, LFS 71% versus 29% (P = .003) and hemoglobin value > or < 8 g/dL, LFS 67% versus 27% (P = .02). Initial CNS involvement had no adverse impact on the outcome. Elderly B-ALL patients (> 50 years) also benefited from this treatment with a CR rate of 56% and a LFS of 56%. It is concluded that this short intensive therapy with six cycles is effective in adult B-ALL. HdM and fractionated higher doses of cyclophosphamide or ifosphamide seem the two major components of treatment.

Adolescent↗
PubMed1996

Effect of iron status on the intestinal absorption of aluminum: a reappraisal.

Clinical and experimental studies have shown that serum aluminum (Al) is bound to transferrin and that cellular uptake of Al appears to be mediated by transferrin receptors. Based on these findings it is widely believed that intestinal Al absorption occurs via iron-specific, transferrin-dependent pathways and that iron (Fe) deficiency increases the intestinal absorption of Al. However, since no transferrin receptors are expressed on the absorptive surface of small intestinal epithelial cells this notion is doubtful. To further clarify the issue the present study investigated the effect of marked alterations of body Fe stores on the intestinal absorption of Al using three different rat models. (I) Serum Al concentrations and urinary excretion rates of Al were measured in iron-overloaded (Fe+) or iron-deficient (Fe-) rats with either normal (C) or impaired (5/6 nephrectomy) renal function (Nx) employing oral A1 loads in single dose studies. (II) Tissue A1 accumulation as well as serum and urine A1 were determined in respective experimental groups exposed to a prolonged (41 days) dietary Al load. (III) To assess the effect of Fe status on the intestinal absorption of Al directly at the organ level perfusions of in situ rat gut preparations were performed. In the single dose studies administration of Al resulted in similar urinary excretion rates of Al in intact kidney groups (C+Fe-, 229 +/- 85 nmol/5 days; C+Fe+, 240 +/- 59 nmol/5 days) despite marked differences in liver Fe (C+Fe-, 1.34 +/- 0.16 vs. C+Fe+, 55.69 +/- 13.20 mumol/g) and duodenal mucosal Fe (C+Fe-, 0.68 +/- 0.11 vs. C+Fe+, 3.17 +/- 0.82 mumol/g). In addition, mucosal Al concentration 24 hours after the load was not affected by the Fe status (C+Fe-, 37 +/- 16 nmol/g, C+Fe+, 56 +/- 19 nmol/g). Regardless of the Fe status post-load Al excretion was enhanced in Nx rats (Nx+Fe-, 533 +/- 234 nmol/five days, Nx+Fe+, 536 +/- 201 nmol/five days). Irrespective of Fe status a prolonged dietary Al load resulted in a similar increase in tissue Al concentration (nmol/g) in liver (baseline, 159 +/- 22; C+Fe-, 276 +/- 125; C+Fe+, 251 +/- 71; Nx+Fe-, 330 +/- 119; Nx+Fe+, 437 +/- 67) and in bone (baseline, 219 +/- 119; C+Fe-, 433 +/- 174, C+Fe+, 485 +/- 141; Nx+Fe-, 504 +/- 185; Nx+Fe+, 548 +/- 215). The increase in spleen Al was significantly larger in Fe-overloaded rats (baseline, 194 +/- 20; C+Fe+, 511 +/- 129 vs. C+Fe-, 308 +/- 62, P < 0.05; Nx+Fe+, 514 +/- 67 vs. Nx+Fe-, 389 +/- 119, P < 0.05). Brain Al tended to rise in Nx rats only (baseline, 96 +/- 33; Nx+Fe+, 174 +/- 100, Nx+Fe-, 156 +/- 78, P = NS). Analogous results were obtained in in situ intestinal perfusion studies: Fe deficiency and Fe overload both did not affect the time-dependent increase in serum Al in either systemic or portal vein blood. When paracellular intestinal permeability was assessed mannitol absorption was significantly higher in uremic animals as compared to controls. Pharmacological blockade (2 mM kinetin) of the paracellular permeability substantially reduced the time-dependent increase in serum Al in uremic rats but had little effect in control animals, suggesting that even the excess absorption of Al observed in uremia occurs via a paracellular rather than an iron-specific pathway. In conclusion, the findings of the present study provide several lines of evidence against the commonly accepted view that the intestinal absorption of Al occurs via iron-specific pathways. Most likely, this is related to the fact, that neither the absorption of Fe nor the absorption of Al are mediated via transferrin receptors. In addition, the enhanced intestinal absorption of Al observed in uremic rats does also not occur via iron-specific pathways, but seems to due to increased paracellular permeability of the intestine.

Aluminum↗
PubMed1995

Long-term ciclosporine A treatment in adults with minimal change nephrotic syndrome or focal segmental glomerulosclerosis.

To evaluate the efficacy and safety of long-term ciclosporine A (CSA) treatment in idiopathic nephrotic syndrome, we prospectively followed immunosuppressive therapy in 22 nephrotic adults for a median of 32 months (range 7-91 months) and obtained repeat renal biopsies. CSA induced complete remission in 60.0% and 14.3% of patients with minimal change nephrotic syndrome (MCNS) (n = 7), respectively. In addition, partial remissions were achieved in 20.0% of patients with MCNS and in 42.9% of patients with FSGS. Resolution of proteinuria was strictly CSA-dependent and no sustained remission occurred following withdrawal, thereby requiring long-term treatment in 18 patients. In 10 patients CSA was administered for more than 43 months. During maintenance therapy the antiproteinuric effect of CSA was preserved and renal function as well as blood pressure remained stable in patients with MCNS, whereas renal function deteriorated in two patients with FSGS due to progression of the underlying renal disease. Renal biopsies revealed slight signs of CSA toxicity in four patients. However, in no case loss of renal function was attributable to these lesions. In conclusion, the present data suggest that long-term maintenance treatment of MCNS with CSA is efficacious and safe at least for a period of up to 43 months. In contrast, CSA has some effect on proteinuria in FSGS, but the results are less favorable.

Administration, Oral↗
PubMed1994

Contrast-enhanced computed tomography for demonstration of bilateral renal cortical necrosis.

Bilateral renal cortical necrosis as a rare form of acute renal failure was encountered in two patients with sepsis and acute renal failure. In both cases contrast-enhanced computed tomography showed characteristic findings: absent specification of the renal cortex and enhancement of subcapsular and juxtamedullary areas and of the medulla without excretion of contrast medium. Establishing an early diagnosis and visualizing the extent of renal cortical necrosis by means of contrast-enhanced computed tomography allow a prognostic evaluation of renal function and further planning of therapy.

Adult↗