Manfred Pollok

Pharmacokinetics of omega-3-fatty acids during ingestion of fish oil preparations

An in vivo comparison of three dosages (3 g, 6 g, 12 g) of two different fish oil preparations in terms of plasma concentrations of their major active components eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was performed. The plasma accumulation was measured during 28 days of ingestion and an equally long wash out period. Data were scrutinized for bioavailability in order to distinguish between the efficiency of the two preparations. Rapid increases in EPA and DHA plasma concentrations can be demonstrated at all dosages during a 28-day ingestion period. EPA accumulated more during ingestion of high than of low dosages of fish oil. DHA revealed almost identical increases and peak values in plasma concentrations in all subgroups. The present data demonstrate dose dependent increases of EPA concentrations whereas DHA plasma concentrations are comparable in all dosages investigated. Measurable EPA and DHA plasma concentration levels are inappropriate means to explain clinical effectiveness. These results were found in both commercially available fish oil preparations. Direct comparison of both preparations revealed no differences in bioavailability.

Ultrafiltration and Hemofiltration: Practical Applications

The modern era of hemofiltration began with its clinical application in 1976. Before that, Henderson and colleagues (1, 2), Quellhorst and associates (3–6), and Dorson and Markowitz (7, 8) had contributed to the physical principles (9, 10), reported first clinical results (6) and recycled purified ultrafiltrate (11). This work would have been inconceivable without the membrane technology developed by industrial firms, such as Amicon (9) and Sartorius (3). The dialysis community became curious about the new technology when in 1976 the first workshop on hemofiltration was held in Braunlage (Table 1) initiated by the German group of Quellhorst. At this meeting a variety of clinical benefits were reported (12) including improvement of anemia, neuropathy, lipid metabolism, hypertension control, hyperparathyroidism and symptomatology. This impressive list of advantages recommended hemofiltration as the panacea in end-stage renal disease (ESRD) treatment. Thereafter industry developed automatic balancing equipment (13) on a volumetric or gravimetric basis and different membranes for flat sheet or hollow fiber filters; simultaneously the complicated dynamics of fluid and solute transfer (9, 10) were elucidated.

The risk of infection following OKT3 and antilymphocyte globulin treatment for renal transplant rejection: results of a single center prospectively randomized trial

Some 43 of 60 (72%) renal allograft recipients who were prospectively randomized to receive either OKT3 monoclonal antibody (n = 30) or ALG (antilymphocyte globulin) polyclonal antibody (n = 30) for steroid-resistant rejection suffered from infection, 25 (83%) following OKT3 and 18 (60%) following ALG treatment (P < 0.05). Clinically evident herpes infection was most frequently seen (9 and 7, respectively), followed by pneumonia (6 and 1, respectively P < 0.05), urinary tract infection and wound infection (2 of each in both groups) fungal (Candida) and multibacterial infections. One patient died in each group due to cytomegalovirus (CMV) pneumonia, giving a mortality of 4.3% in each group. Actuarial 1-year graft and patient survival rates were 80% and 97% in both groups, respectively. It is concluded that ALG and OKT3 are equally effective in renal allograft rejection resistant to steroid treatment, however, the risk of infection appears to be higher with OKT3.

Gestörte alpha2-Adrenozeptorfunktion bei Hämodialysepatienten mit renaler Anämie — eine mögliche Ursache der Blutdrucksteigerung unter rekombinantem humanem Erythropoietin?

SummaryNine patients on maintenance hemodialysis and transfusion-demanding renal anemia (group A) were treated with rHuEPO 120 IU/kg i.v. three times per week. Hemoglobin-content was raised from 7.2±0.9 to 10.4±0.8 g/dl. In all patients blood pressure rose, three patients developed arterial hypertension. Mean diastoloic blood pressure was 66±12 and 78±16 mmHg (p<0.001) before and after rHuEPO. Rise in blood pressure was accompanied by a significant fall in plasma-noradrenaline-levels (from 498±100 to 383±75 pg/ml;p<0.05) and alpha2-adrenoceptor-density (from 574±76 to 384±49;p<0.05). Compared to nine patients on maintenance hemodialysis and hematocrit over 30% (group B), patients with severe renal anemia (group A before treatment) had higher densities of alpha2-adrenoceptors (574±76 vs. 218±32;p<0.001) despite higher plasma-noradrenaline-levels (498±100 vs. 399±63; n.s.). We suppose a anemia-related disturbance of alpha2-receptor-function with the result of abolished receptor down-regulation and impaired vascular reagibility to vasoconstricting stimuli. With the correction of anemia receptor-function improves, receptor down-regulation as well as vascular reagibility is re-established resulting in augmented vascular resistance and higher blood pressure.Nine patients on maintenance hemodialysis and transfusion-demanding renal anemia (group A) were treated with rHuEPO 120 IU/kg i.v. three times per week. Hemoglobin-content was raised from 7.2 +/- 0.9 to 10.4 +/- 0.8 g/dl. In all patients blood pressure rose, three patients developed arterial hypertension. Mean diastoloic blood pressure was 66 +/- 12 and 78 +/- 16 mmHg (p less than 0.001) before and after rHuEPO. Rise in blood pressure was accompanied by a significant fall in plasma-noradrenaline-levels (from 498 +/- 100 to 383 +/- 75 pg/ml; p less than 0.05) and alpha 2-adrenoceptor-density (from 574 +/- 76 to 384 +/- 49; p less than 0.05). Compared to nine patients on maintenance hemodialysis and hematocrit over 30% (group B), patients with severe renal anemia (group A before treatment) had higher densities of alpha 2-adrenoceptors (574 +/- 76 vs. 218 +/- 32; p less than 0.001) despite higher plasma-noradrenaline-levels (498 +/- 100 vs. 399 +/- 63; n.s.). We suppose a anemia-related disturbance of alpha 2-receptor-function with the result of abolished receptor down-regulation and impaired vascular reagibility to vasoconstricting stimuli. With the correction of anemia receptor-function improves, receptor down-regulation as well as vascular reagibility is re-established resulting in augmented vascular resistance and higher blood pressure.

Enalapril and losartan augment endogenous nitric oxide release in Takayasu's arteritis--a case report.

Prognosis in Takayasus arteritis is limited owing to renovascular hypertension. The authors report a patient with Takayasus arteritis who had been unilaterally nephrec tomized and presented with malignant hypertension due to renal artery stenosis. Hypertension was refractory to conventional antihypertensive treatment, and stenosis was not accessible by interventional angioplasty. Initiation of enalapril and losartan therapy was successful in improving blood pressure without deterioration of renal function due to ischemic failure. Antihypertensive treatment resulted in dramatically stimulated endogenous nitric oxide (NO) synthesis, while elevated plasma endothelin-1 levels were unchanged. Renovascular hypertension in Takayasus arteritis is associated with an imbalance of vasoconstrictor peptide endothelin-1 and vasodilator peptide NO. Successful treatment of hypertension by enalapril or losartan results in improved endoge nous NO synthesis, which putatively counterbalances excessive vasoconstrictor actions and may retard the progression of renal failure.

Spontaneous tendon rupture after ofloxacin treatment in renal transplant recipients on high-dose corticosteroids

Abstract Acute tendon rupture without any history of trauma, a rare complication occurring mainly in metabolic diseases, is increasingly reported after treatment with fluoroquinolones. We report here on the occurrence of Achilles tendinitis and Achilles tendon rupture after ofloxacin treatment for uncomplicated urinary tract infection in four patients receiving high-dose corticosteroid treatment after renal organ transplantation and compare them with a control group without this complication. Patients experiencing tendon rupture had been on regular dialysis treatment for 54.5 ± 39.5 months before receiving cadaveric kidney transplants. All had secondary hyperparathyroidism, with parathyroid hormone levels ranging from 247 to 707 ng/L, had low or normal serum phosphate levels (1.21 to 2.69 mg/dL), and had moderately elevated alkaline phosphatase levels (75 to 285 U/L). Tendon ruptures occurred at a median of 49 days after organ transplantation and 15.3 ± 9.6 days after initiation of quinolone treatment. Mean time of treatment was 5 days. All patients received triple-regimen immunosuppression consisting of methylprednisolone, cyclosporin A, and mycophenolate mofetil. Transplant function was stable, and none had experienced transplant rejection. Mean ingestion of prednisolone ranged from 6 to 16 mg/d, and mycophenolate mofetil from 1 to 2 g/d; cyclosporin A serum levels were 208 ± 76 μg/L. After kidney transplantation, spontaneous large tendon rupture after quinolone treatment is deleterious during the early posttransplantion phase. Secondary risk factors are high-dose corticosteroid treatment and history of secondary hyperparathyroidism. Quinolones should be restricted for treatment of severe urinary tract infection only, which failed to respond to other antibiotic regimens in the early posttransplantation period after kidney transplantation under high-dose corticosteroid treatment.