[Prevalence of Pulmonary Hypertension in Dialysis Patients with End-stage Renal Disease]. / Prävalenz der pulmonalen Hypertonie bei Dialysepatienten mit terminaler Niereninsuffizienz.

BACKGROUND: In patients with end-stage renal disease (ESRD), pulmonary hypertension (PH) is a frequent complication with different etiologies and a 17 - 56 % prevalence rate. We evaluated the impact of fluid retention measured by bioimpedance on the prevalence of PH in this patient cohort. METHODS: All patients with ESRD at the dialysis center of the Medical Clinic II of the University Hospital Gießen were invited to participate in the study and undergo non-invasive PH screening. If the screening suggested PH, patients underwent bioimpedance spectroscopy for measurement of fluid retention followed by adjustment of fluid levels to normovolemia as far as possible. Thereafter a second non-invasive screening was performed in this patient cohort after reaching normovolemia. If signs for PH persisted, patients underwent right heart catheterization for further assessment. RESULTS: 52 patients agreed to participate in the study. After the first noninvasive screening, PH was suspected in 12 patients (23 %). After adjustment of fluid levels to reach normovolemia, PH was suspected only in 4 patients (7.7 %) with confirmation in 2 patients by right heart catheterization (3.8 %). DISCUSSION: In patients with ESRD, PH is frequently associated with fluid retention as shown by bioimpedance spectroscopy. After adjustment of fluid to normal levels, PH was confirmed by invasive test in nearly 4 % of cases.

Improvement of complex regional pain syndrome after plasmapheresis.

Complex regional pain syndrome is a severe complication following trauma that is associated with vasomotor, sudomotor and sensory disturbances in an affected limb or region of the body. The exact physiopathology is not fully understood yet. Recently, autoantibody findings suggested an immune-mediated physiopathology of the disease. We here describe two otherwise treatment-resistant patients with complex regional pain syndrome and high-titre beta2 adrenergic receptor autoantibodies, who did respond to plasmapheresis. Both patients showed strong improvement of pain and autonomic symptoms measured by impairment level sum score.

The risk of polyomavirus-associated graft nephropathy is increased by a combined suppression of CD8 and CD4 cell-dependent immune effects.

Polyomavirus-associated graft nephropathy (PAN) has emerged as a significant risk factor for kidney graft loss. We analyzed intracellular cytokine responses for possible protective versus permissive immunologic effects on BK-virus replication. One hundred five renal transplant patients included in a prospective single-center study were randomized to receive cyclosporine mycophenolate mofetil (MMF) (CM: n = 31), tacrolimus (Tac)/MMF (TM: n = 32) or Tac/MMF with conversion to everolimus (TErl; n = 32). Ten patients were not randomized (NR) due to contraindications to MMF. The immunosuppressive therapy was monitored pre- and posttransplantation at 4, 12, and 24 months using triple fluorescence flow cytometry for intracellular interleukin (Il)-2 Il-4 and interferon (IFN)-γ production in phorbol myristate acetate- and lipopolysaccharide- stimulated lymphocyte cultures. BK viremia screening was performed by reverse-transcriptase polymerase chain reaction testing on days 0, 14, 30, 60, 90, 120, 180, 270, 360, and 720. Seven of 105 (6.7%) patients developed biopsy-proven PAN (CM: n = 1, TM: n = 3, TErl: n = 2, NR: n = 1), among whom 4 lost their grafts (TM: n = 1, TErl: n = 2, NR: n = 1). Twenty-one of 105 (20.0%) patients had documented BK viremia. BK viremia which preceded PAN in all cases, was significantly associated with TM immunosuppression: 4/31 (12.9%) CM: 11/32 (34.4%) TM; 5/32 (15.6%) TErl, and 1/10 (10.0%) NR patients (P = .034). BK-viremic patients showed significantly diminished CD8(+) T-cell Il-2 production at 120 days (P = .011) and 1 year posttransplantation (P = .014) compared with non-BK-viremic patients. Patients with PAN displayed significantly lower CD4(+) T-cell Il-4 responses at 1 and 2 years after transplantation (1 year: P = .007; 2 years: P = .001) with diminished IFN-γ responses at 1 year after transplantation (P = .011). Our analysis showed the incidence of BK viremia to be increased among patients with defective cytotoxic CD8(+) T-cell -dependent immune reactivity. Recipients who progressed from BK viremia to overt PAN showed an additional immunologic defect in CD4(+) T-cell function. Patients on a Tac- plus MMF-based immunosuppression were at higher risk to develop BK viremia.

Impact of pretransplant intravenous immunoglobulin administration on anti-AB0 antibody levels in AB0-incompatible living donor kidney transplantation.

BACKGROUND: From March 2007 to July 2010, we performed 14 AB0-incompatible (AB0i) living kidney transplantations using donor blood group-specific immunoadsorption (IA), anti-CD20 monoclonal antibody, and intravenous immunoglobulin (IVIG) pretreatment. METHODS: To analyze the effect of a presumed anti-donor blood group-specific antibody transfer by IVIG administration (0.5 g/kg; 5.4 ± 0.9 days pretransplant), we assessed AB0i antibody titers in different IVIG preparations and evaluated their impact on patient AB0i antibody titers. RESULTS: AB0i antibody IgG titers before treatment ranged from 8 to 1024. We performed 6.9 ± 1.1 IA procedures pretransplant to reach AB0i antibody titers ≤4, which enabled successful transplantation in all pretreated patients. Their mean serum creatinine at discharge was 1.5 ± 0.1 mg/dL. IVIG preparations differed profoundly in their AB0i antibody titers: The lowest titers were observed in Sandoglobulin preparations (1-8) compared with Intratect (2-128), Octagam (4-32) and Gamunex (2-512). Usually, administration of the IVIG preparation containing the lowest isoagglutinin titer resulted in low AB0i antibody titer increments in patient sera: Sandoglobulin, 2 titer steps (n = 2), 1 titer step (n = 1), and 0 titer steps (n = 5). In contrast, Octagam showed 0 titer steps (n = 2) and Intratect, 0 titer steps (n = 3). However, after Gamunex administration, the AB0i antibody titer of 8 and the AB0i antibody titer rose 3 titer steps (16 to 128; n = 1), which could not be explained by passive transfer of isoagglutinin alone. CONCLUSION: Our data showed that the choice of IVIG preparation with the lowest AB0i antibody levels is a time- and cost-sparing step in the pretreatment of AB0i living donor kidney recipients. Posttransplant, a high isoagglutinin content within the IVIG preparation has the potential to induce antibody-mediated rejection.

Postoperative bleeding after AB0-incompatible living donor kidney transplantation.

BACKGROUND: Since 2007, we have performed 14 AB0-incompatible (AB0i) living kidney transplantations to increase the number of living kidney transplantations. METHODS: To prevent clotting, donor kidneys were perfused with an HTK/heparin solution with heparin washed out immediately pretransplantation. However, in 4/14 recipients, significant postoperative diffuse hemorrhage occurred with the need for surgical intervention in 3 patients. To analyze the cause of postoperative diffuse bleeding, sequentially before and after opening the graft anastomosis, we prospectively performed coagulation studies: partial thromboplastin time (PTT), thrombin time, thromboplastin time, fibrinogen, antithrombin, D-dimers, plasminogen, and thrombelastography. RESULTS: We found no clotting disturbances owing to blood group-specific immunoadsorption. However, 3/4 patients with bleeding complications showed elevated PTT values even 2 hours after opening the anastomosis, which was proven to be a heparin effect by in vitro application of heparinase. Hyperfibrinolysis and disturbances of platelet aggregation were not detected. Because of these results, we lowered the heparin dose administered after donor nephrectomy from initially 10,000-20,000 to 4000 IU resulting in significantly lower PTT values at 2 hours (34.6 ± 4.5 s among patients 6-14 vs 69.0 ± 16.3 s among patients 1-5; P = .012). There were no further bleeding complications. Lowering the heparin dosage had no impact on graft function: serum creatinine at discharge of 1.5 ± 0.1 versus 1.6 ± 0.2 mg/dL. CONCLUSION: Our data indicated that postoperative hemorrhage after AB0i kidney transplantation was associated with the amount of heparin used for graft perfusion after donor nephrectomy. The use of antifibrinolytic agents may be harmful; no hyperfibrinolysis takes place in the AB0i transplant setting.

Surfactant subtype conversion is related to loss of surfactant apoprotein B and surface activity in large surfactant aggregates. Experimental and clinical studies.

Conversion of the highly surface-active subtype of pulmonary surfactant known as large surfactant aggregates (LA) to small aggregates (SA) with poor surface activity has recently been shown to occur upon cyclic changes of the air-liquid interface area in vitro. By subjecting pooled rabbit bronchoalveolar lavage fluid (BALF) to this maneuver, we found that conversion of LA to SA was accompanied by a marked decline in the ability of the remaining LA fraction to reduce surface tension by adsorption and during film compression on a pulsating bubble surfactometer. SA obtained by centrifugation of noncycled rabbit BALF had a similar phospholipid (PL) but different neutral lipid (NL) composition than did the LA. Upon cycling, the increased formation of SA obliterated this difference. No substantial difference in the PL, NL, or fatty acid profile of LA was noted before and after cycling. In contrast, the content of surfactant apoprotein-B (SP-B) in the LA decreased dramatically to nearly undetectable levels during the cycling maneuver, and this decline in SP-B content was closely correlated with the decrease in proportional appearance of LA and loss of surface activity of this fraction. Reconstitution of LA with intact SP-B after cycling virtually fully restored the surface activity of this surfactant subtype. When comparing lavage samples from adults with acute respiratory distress syndrome (ARDS; n = 10) with samples from healthy controls (n = 11), we noted a marked reduction of SP-B in the LA fraction. There was a significant correlation between the SP-B content of the LA fraction and the relative percentage of LA in BALF or the lower surface activity of this surfactant subtype. We conclude that an SP-B-related loss of LA integrity and function may substantially contribute to the decline of this surfactant subtype and the loss of its surface activity during cycling in vitro and in clinical ARDS.

Investigations of trace elements in metastases and primary carcinoma of the prostate.

The concentration of several trace elements (Cd, Zn, Mn, Cr, Pb, Se) as determined both in primary prostatic carcinoma and in metastases of the same patients in unseparated and in separated tissue. In the unseparated tissue a significantly higher amount of all elements studied was found in the primary tumour. Different results were obtained for the concentrations in separated epithelium and stroma as well as in the cellular fractions of metastases and of primary tumour.

Serum-Zn-levels in prostatic cancer.

Zinc in serum of both patients with prostatic carcinoma and men without prostatic cancer was analyzed by flame atomic absorption spectrometry (FAAS). No significant differences were found between the group with prostatic carcinoma without metastasis and the group used for comparison. The Zn level in serum of patients with both prostatic carcinoma and metastases was decreased in comparison to the other groups. A decrease in the Zn concentration was also found for men without metastases after orchiectomy and hormone therapy.

Zinc, cadmium and selenium concentrations in separated epithelium and stroma from prostatic tissues of different histology.

The concentration of Zn, Cd and Se in unseparated tissues and epithelial and stromal fractions of normal prostate gland, BPH and prostatic carcinomas of different histological grading were determined by flameless AAS. There were distinct differences in the content of Zn, Cd and Se in the epithelial and stromal fractions depending on histology. In all cases the concentration of these elements in the epithelial fractions was higher than in stromal fractions. These differences are discussed.

Studies of Cd, Zn and Cu levels in human kidney tumours and normal kidney.

The distribution of Cd, Zn and Cu was analyzed in nuclear, mitochondrial and cytosol cellular fractions of renal tumours and normal surrounding kidney tissues by electrothermal atomic absorption spectrometry (AAS). The normal kidney tissues were separated into cortical and medullary parts. A significant decrease of the Cd-levels was found in all cellular fractions from normal kidney to tumour tissues (hypernephroma). The Zn values varied strongly. We noted a slight decrease of Zn levels in renal tumour. The Cu concentration in the nucleus of kidney tumours was significantly increased.

Zinc and cadmium plasma and erythrocyte levels in prostatic carcinoma, BPH, urological malignancies, and inflammations.

Zinc and cadmium in both serum and erythrocytes from patients with prostatic carcinoma of different histologies, BPH, other urological tumors, and pyelonephritis were analyzed by atomic absorption spectrometry. The variance of the results obtained was very high for each group. No significant differences in the Zn or Cd concentration in either the blood plasma or the erythrocytes could be found between any of the different groups of patients. There were also no trends to be seen in the concentrations of these elements in human blood over a period of months. We conclude that the concentration of Zn and Cd in serum or erythrocytes are not an index for the diagnosis or therapy of prostatic carcinoma, BPH, urological malignancy, or inflammations.

Zinc and cadmium in cell fractions of prostatic cancer tissues of different histological grading in comparison to BPH and normal prostate.

The concentrations of zinc and cadmium in cellular fractions of normal prostate gland, BPH and prostatic carcinomas of different histological grading were determined by electrothermal atomic absorption spectrometry. We found distinct differences in the content of Zn and Cd in the nuclear fractions of malignant tissues in comparison with BPH and normal prostatic tissues. The highest values of Cd were obtained in the nuclear fractions of poorly-differentiated carcinomas. In these samples we also found a low concentration of zinc. In comparison to this the highest Zn-values were found in the nuclear fraction of the BPH.

Determination of the distribution of zinc and cadmium in cellular fractions of BPH, normal prostate and prostatic cancers of different histologies by atomic and laser absorption spectrometry in tissue slices.

The distribution of Zinc (Zn) and Cadmium (Cd) was analyzed in nuclear, mitochondrial and cytosol cellular fractions of prostatic carcinoma of different histological grading, BPH and normal prostate by electrothermal atomic absorption spectrometry (AAS). Distinct differences in Zn and Cd concentration in carcinomatous material in comparison with BPH and normal prostates was found. The highest concentration of Cd and the lowest level of Zn were found in poorly differentiated carcinomas. The results in cellular fractions were compared with investigations on Zn and Cd distribution in prostatic slices by laser AAS.

Zinc and cadmium concentration in prostatic carcinoma of different histological grading in comparison to normal prostate tissue and adenofibromyomatosis (BPH).

Zn and Cd concentrations in tissue of normal prostate gland, BPH and prostatic carcinoma of different histological grades have been determined by atomic absorption spectrometry before therapy. We found a distinct biological antagonistic effect between Zn and Cd in the human prostate gland. We have seen an increasing amount of Zn in BPH, but a decrease in prostatic cancer. In contrast, we found a continuous increase of cadmium concentration from the normal prostate via BPH through carcinoma.

[Fibrinolysis in prostate carcinomas of varying grades of differentiation with respect to estrogen therapy and castration]. / Die Fibrinolyse bei Prostatakarzinomen verschiedener histologischer Differenzierungsgrade unter Berücksichtigung der gegengeschlechtlichen Hormonbehandlung und Kastration.

In 21 patients with histologically ascertained carcinoma of the prostate before the beginning of the oestrogen therapy the rate of fibrinolysis and the time of euglobulinolysis were determined. In more than two thirds of the cases an increased rate of fibrinolysis was found, 4 cases of them showed a shortening of the time of euglobulinolysis. The rate of fibrinolysis was in all 21 patients on an average 61%. In the 12 patients with increased rate of fibrinolysis it was on an average 89%. After the oestrogen therapy a reduction to on an average 49% could be stated.

[On the histotopochemistry of prostaglandin F2 alpha metabolizing enzymes in rat kidney (author's transl)]. / Zur Histotopochemie Prostaglandin F2 alpha-abbauender Enzyme der Rattenniere.

Using PGF2 alpha as substrate we have investigated the demonstration and localization of NAD- and NADP-15-hydroxyprostaglandin dehydrogenase in the kidney of developing and adult rat kidney. Under histochemical conditions an adequate demonstration of the soluble PGDH in native sections is possibly by membrane incubating technic in presence of specific coenzymes. The effectors PMS and KCN showed a decreasing effect on the enzyme activity. In the developing and adult rat kidney the activity of NAD-PGDH was localized predominantly to medullary rays and inner cortex. We have found the reaction product in the following kidney substructures: Pars recta tubuli, distal convoluted tubule, ascending limb of Henle, collecting tubule and lower in proximal convoluted tubule and in the glomerular cells. The NADP-PGDH was localized only in the cortex structures, but the reaction was uneven and the localization of the reaction product was diffuse. The results are discussed in connection with the specificity of the reaction.