Robot-assisted resection of ectopic kidney in children: An anatomical illustration.

INTRODUCTION: Failure of kidney migration during embryonic life results in an ectopic kidney, with an incidence varying from 1 in 500 to 1 in 1200. Pelvic kidney can be a rare cause of recurrent urinary tract infection (UTI), warranting nephrectomy in some cases. MATERIAL AND METHODS: A 7-year-old girl with a history of recurrent UTIs and vaginal discharge was diagnosed with a dysplastic afunctional ectopic kidney located in the pelvis, with ureter draining into the cervix or vaginal wall. RESULTS: A robot-assisted approach was chosen, with side docking of the robot to allow concurrent vaginoscopic/hysteroscopic exploration. A uterus bicornis was found. The ectopic ureter was dissected toward its drainage in the vaginal wall, where it was sutured and resected. The dysplastic kidney and ureter were removed. Compared to pure laparoscopic approach, dissection deep into the pelvis toward the vaginal wall is aided by the robotic dexterity and facilitates complete resection of the structure, which avoids leaving a ureteric stump into the vaginal wall. CONCLUSIONS: Robot-assisted surgery is a safe and effective option for resection of ectopic kidneys with ectopic ureter in children. Dissection up until the vaginal wall in children is aided by robotic dexterity, making this kind of surgery the ideal indication for robotic-assisted surgery.

Urethroplasty for urethral injuries and trauma-related strictures in children and adolescents: a single-institution experience.

INTRODUCTION: Urethral injuries and trauma-related strictures (UITSs) in children are rare. The treatment is challenging but crucial to avoid life-long urinary complications such as recurrent stricture formation, urinary incontinence, and impotence. OBJECTIVE: The aim was to report on the surgical and functional outcome of urethroplasty for UITSs and to provide data on patient-reported outcome measures (PROMs). MATERIAL AND METHODS: Between November 2001 and October 2017, 18 male children (≤18 years; median: 13 years) underwent urethroplasty for UITSs at a single tertiary referral center. Etiology was iatrogenic in five (27.8%), perineal straddle injury in six (33.3%) and pelvic fracture urethral injury (PFUI) in seven (38.8%) patients. PFUIs and short (≤3 cm) bulbar strictures were treated by transperineal anastomotic repair (n = 15; 83.3%), whereas a long bulbar stricture and a penile stricture were treated by, respectively, a preputial skin graft and flap urethroplasty. A penetrating penile urethral injury during circumcision underwent early exploration with primary repair of the laceration. Failure was defined as need for additional urethral instrumentation. PROMs were sent to patients ≥16 years at the latest evaluation. RESULTS: Median follow-up was 57 (range: 8-198) months. No complications and grade 1, 2, and 3 were present in, respectively, 13 (72.2%), two (11.1%), one (5.6%), and two (11.1%) patients. The success rate in a tertiary referral center was 94.4%. An immediate failure was observed in a patient with a PFUI and concomitant bladder neck injury. PROMs were available in 12 patients. Four patients (33.3%) reported erectile dysfunction. Post-void dribbling (25%) and urgency (50%) were the most frequently reported complaints. All patients were satisfied after urethroplasty and stated that they would undergo the surgery again. DISCUSSION: This series corroborates the recent trend in favor of transperineal anastomotic repair for PFUI, with combined abdominoperineal approach reserved for complex situations (e.g. bladder neck injury). For anterior UITSs, adaption of the technique to the characteristics of UITSs (etiology, location, length, and quality of graft bed) yielded excellent outcomes. Future systematic use of PROMs is also needed in children to elucidate the impact of urethroplasty on the urinary and sexual function. CONCLUSION: External trauma is the most important etiology of UITSs, but iatrogenic causes should not be neglected. Urethroplasty, mainly by anastomotic repair (AR) but with the technique adapted to local stricture characteristics if necessary, has an excellent long-term success rate in experienced hands. Functional disturbances are frequent, but despite this, patient satisfaction is high after urethroplasty.

Excision and Primary Anastomosis for Short Bulbar Strictures: Is It Safe to Change from the Transecting towards the Nontransecting Technique?

OBJECTIVE: To explore whether it is safe to change from transecting excision and primary anastomosis (tEPA) towards nontransecting excision and primary anastomosis (ntEPA) in the treatment of short bulbar urethral strictures and to evaluate whether surgical outcomes are not negatively affected after introduction of ntEPA. MATERIALS AND METHODS: Two-hundred patients with short bulbar strictures were treated by tEPA (n=112) or ntEPA (n=88) between 2001 and 2017 in a single institution. Failure rate and other surgical outcomes (complications, operation time, hospital stay, catheterization time, and extravasation at first cystography) were calculated for both groups. Potentially predictive factors for failure (including ntEPA) were analyzed using Cox regression analysis. RESULTS: Median follow-up for the entire cohort was 76 months, 118 months, and 32 months for, respectively, tEPA and ntEPA (p<0.001). Nineteen (9.5%) patients suffered a failure, 13 (11.6%) with tEPA and 6 (6.8%) with ntEPA (p=0.333). High-grade (grade ≥3) complication rate was low (1%) and not higher with ntEPA. Median operation time, hospital stay, and catheterization time with tEPA and ntEPA were, respectively, 98 and 87 minutes, 3 and 2 days, and 14 and 9 days. None of these outcomes were negatively affected by the use of ntEPA. Diabetes and previous urethroplasty were significant predictors for failure (Hazard ratio resp. 0.165 and 0.355), whereas ntEPA was not. CONCLUSIONS: Introduction of ntEPA did not negatively affect short-term failure rate, high-grade complication rate, operation time, catheterization time, and hospital stay in the treatment of short bulbar strictures. Diabetes and previous urethroplasty are predictive factors for failure.

Multiple Injuries to the Lower Urinary Tract: Two Cases and Comparison with the EAU Guidelines.

Blunt trauma to the lower urinary tract is usually associated with pelvic fractures. The European Association of Urology (EAU) provides guidelines to diagnose and treat these injuries. The guidelines summarise the available evidence and provide recommendations on diagnosis and treatment of these patients. Therefore, these guidelines are important adjuncts to the urologist and emergency physician in the clinical decision-making. However, strict adherence to the guidelines is not always easy or possible because of concomitant injuries obscuring the clinical picture. This is illustrated by two case reports of concomitant injuries of the lower urinary tract (bladder with urethral injury). The clinical decisions will be discussed point by point and should serve as a practical teaching moment for the reader.

The anti-proliferative effect of calcitriol on HL-60 cells is neutralized by uraemic biological fluids.

BACKGROUND: It has been demonstrated that uraemic serum/ultrafiltrate inhibits cell-mediated immune response in vitro, and that it suppresses calcitriol synthesis and its biological actions. METHODS: In the present in vitro study, the effect of calcitriol, uraemic ultrafiltrate (UUF) and a combination of both on the human promyelocytic leukaemia cell line, HL-60, was studied by evaluating bromodeoxyuridine (BrdU) incorporation into the DNA, luminol-amplified chemiluminescence (CL) production, expression of CD14, and levels of vitamin D receptor mRNA (VDR mRNA) and CD14 mRNA. RESULTS: The ability of calcitriol to block cell proliferation (37.4+/-5.4 to 30.5+/-5.6% cells incorporating BrdU, P:<0.01) was neutralized when UUF was applied together with calcitriol (53.4+/-21.3% cells incorporating BrdU, P:<0.01 vs calcitriol alone). Similarly to what was observed for BrdU incorporation, the CL production of HL-60 cells was enhanced in the presence of calcitriol (20126+/-10154 to 61528+/-24021 cpm, P:<0.01), and was suppressed again in the presence of calcitriol and UUF (20916+/-12075 cpm, P:<0.01 vs calcitriol alone); finally UUF also inhibited the calcitriol-induced CD14 expression (71.1+/-11.2 to 54.9+/-17.7% CD14 positive cells, P:<0.05). On the other hand, the calcitriol-induced CD14 mRNA levels were not significantly different in the presence of calcitriol and UUF compared to calcitriol alone. This points to an inhibition by UUF at a post-transcriptional level. Similar data were found for VDR mRNA levels. UUF was fractionated by HPLC in four fractions, hydrophilic uraemic solutes being eluted first (F1) and hydrophobic solutes being eluted last (F4); fractions 1, 2 and 3 simultaneously affected both BrdU incorporation and CL production in a significant way. CONCLUSIONS: It is concluded that UUF contains factors that impair calcitriol-activated function of HL-60 cells. Hence, the differentiation and immune response of these promyelocytic leukaemia cells, as induced by the supplementation of calcitriol, is neutralized in the presence of uraemic biological fluids. This may be of relevance for the propensity to infection and malignancy of the uraemic patient.

Vitamin E-bonded cellulose membrane and hemodialysis bioincompatibility: absence of an acute benefit on expression of leukocyte surface molecules.

Dialysis with unmodified cellulose membranes is associated with such bioincompatibility phenomena as leukopenia, increased expression of adhesion molecules on leukocytes, and release of reactive oxygen species. Dialysis biocompatibility can be improved by modifications in the structure of the cellulose membrane to diminish leukocyte activation and/or protect against the released free oxygen radicals. Excebrane (Terumo Corp, Tokyo, Japan) is a vitamin E-modified cellulose membrane. In the present study, the effect of dialysis with Excebrane membranes on granulocyte and monocyte counts; CD11b, CD11c, and CD45 expression on the surface of granulocytes; and CD14 expression on monocytes was evaluated and compared with low-flux polysulfone membranes. Fifteen minutes after the start of dialysis, granulocytopenia and monocytopenia were more pronounced with the Excebrane membrane compared with polysulfone. The increase in basal expression of CD11b and CD45 on circulating granulocytes was more pronounced during dialysis with Excebrane than polysulfone membranes. Regarding the increased expression on in vitro stimulation with phorbol myristate acetate, blunted upregulation was obtained during dialysis using Excebrane membranes for CD11c and CD45 expression on granulocytes and CD14 expression on monocytes. In conclusion, such indices of membrane bioincompatibility as leukocyte counts and expression of leukocyte surface molecules show more profound alterations with Excebrane than the standard low-flux polysulfone membrane in both basal and in vitro activated states.

Effect of regional citrate anticoagulation on leukopenia, complement activation, and expression of leukocyte surface molecules during hemodialysis with unmodified cellulose membranes.

BACKGROUND: Dialysis with complement-activating membranes is associated with leukopenia, which is related to an increased expression of adhesion molecules on leukocytes. Citrate chelates calcium and has been claimed to attenuate leukopenia. METHODS: In this study, the effects of citrate anticoagulation on leukocyte and granulocyte counts, complement activation, and the expression of CD11b, CD11c, and CD45 on the surface of granulocytes were evaluated during hemodialysis with unmodified cellulose membranes. Standard heparin was compared to citrate in three different schedules: citrate was infused to obtain a concentration of either 7 or 10 mmol/l blood. CaCl(2) was administered into the dialyzer outlet at 8. 25 mmol Ca(2+)/h (citrate 10 mmol/l) or at 11 mmol Ca(2+)/h (citrate 7 and 10 mmol/l) to reconstitute the calcium levels in the blood returning to the patient. RESULTS: The use of citrate at a high concentration (10 mmol/l) was associated with a blunted upregulation of CD11b, both at the inlet and at the outlet bloodline; for CD11c a reduced upregulation was observed on granulocytes harvested from the inlet bloodline. No effects of citrate were observed on leukopenia, granulocytopenia, or complement activation. A positive correlation between the decrease in systemic ionized Ca(2+) concentration and the increase in CD11b and CD11c expression was found. CONCLUSION: Citrate/CaCl(2) administration affects leukocyte adhesion molecule expression in a dose-dependent way; however, no significant effect could be demonstrated on leukopenia and complement activation.

Effect of radiographic contrast agents on leukocyte metabolic response.

BACKGROUND: The use of radiographic contrast media in the setting of possible bowel ischemia and potential perforation is known to carry a risk of morbidity and mortality. However, studies of the effect of available contrast media on host immunological defense mechanisms are lacking. We have examined the effect of barium and of two water-soluble contrast agents of differing iodine concentration and osmolality, Conray 30 and Cysto Conray II, on leukocyte phagocytosis. MATERIALS AND METHODS: Blood samples were incubated with the contrast media alone (termed the "resting state"), and in combination with a standard phagocytic challenge (Zymosan polysaccharide extract) and with Staphylococcus epidermidis, Streptococcus faecalis and Escherichia coli, to determine the effect of contrast media upon leukocyte phagocytic response. Incubation with saline was used as control. In the case of barium, the "resting state" and standard challenge experiments were repeated at nine dilutions, ranging from 1:1 to 1:1000. The leukocyte phagocytic response was measured in two ways: CO2 generation (an index of metabolic activity) and chemiluminescence (an index of generation of reactive oxygen species and bacterial killing). RESULTS: Barium, at clinical dilutions, causes a significant increase of baseline "resting state" phagocytic activity, which in turn leads to significant blunting of subsequent response to phagocytic challenge and adversely affects the response to all bacteria tested. There is no baseline activation of leukocytes by the water-soluble media, although there was some inhibition (rather than activation) of leukocyte metabolic activity. The effect of the water-soluble media on bacteria was more complex (although inhibition is minor compared to barium). CONCLUSIONS: Our data demonstrate that barium is a significant activator of phagocytic cells, which results in deactivation of phagocytic response when challenged; these data serve to explain the enhanced adverse effect of barium in cases of fecal peritonitis.

Citrate anticoagulation does not correct cuprophane bioincompatibility as evaluated by the expression of leukocyte surface molecules.

BACKGROUND: Citrate, used for the anticoagulation of the extracorporeal dialysis circuit, reduces ionized calcium by chelation and has been claimed to attenuate dialyser membrane bioincompatibility. Dialysis with complement-activating cuprophane membranes is associated with leukopenia which has been related to an increase in adhesion molecule expression on the surface of circulating leukocytes. METHODS: The effect of citrate anticoagulation on the expression of CD11b, CD11c and CD45 on the surface of granulocytes and CD14 on monocytes during haemodialysis with cuprophane membranes, was evaluated by flow cytometric analysis. A comparison of standard heparin vs citrate was performed in 14 chronic haemodialysis patients. During citrate anticoagulation a calcium-free dialysate was used and citrate was infused to obtain a concentration of 4.3 mmol/l blood. The unchallenged 'baseline state' expression of the surface molecules and the increase after ex vivo stimulation with phorbol 12-myristate 13-acetate (delta-PMA) or formyl-methionyl-leucyl-phenylalanine (delta-fMLP) was studied. RESULTS: With heparin, as well as with citrate, a sharp fall in granulocyte and monocyte count was observed after 15 min of dialysis, followed by a recovery at the end of the session. The expression of CD11b, CD11c and CD45 on granulocytes increased markedly during cuprophane dialysis with a peak at 15 min; there were no differences in response between heparin and citrate anticoagulation. Delta-PMA and delta-fMLP for CD45, CD11c and CD14 showed a decrease during cuprophane dialysis vs t0; again there were no differences between heparin and citrate. CONCLUSION: We conclude that the use of citrate was not associated with reduced leukocyte activation as measured by the expression of surface molecules during cuprophane dialysis and that no effect on dialysis leukocytopenia could be registered.

In vitro effect of cefodizime, imipenem/cilastatin and co-trimoxazole on dexamethasone and cyclosporin A depressed phagocytosis.

Phagocytosis is an important part of the host defense against infection. Antibiotics can influence phagocytic function. In the present study, leukocyte metabolic response to phagocytic challenge by latex was assessed in relation to in vitro addition of cotrimoxazole, imipenem/cilastatin, cefodizime, dexamethasone (DXM), and/or cyclosporin A (CsA). Using latex particles as phagocytic challenge, glucose-1-14C utilization and 14CO2 production were measured by liquid scintillation counting. The phagocytic response was impaired by in vitro addition of DXM or CsA and this setup was used as an experimental model of immunodepression. The addition of co-trimoxazole to control samples (without DXM or CsA) depressed the response to latex challenge, whereas imipenem and cefodizime had a neutral effect. In the presence of DXM, co-trimoxazole induced a further decrease. The depressive effect of DXM was partially neutralized in the presence of cefodizime. With CsA depression, co-trimoxazole also induced a further decrease, imipenem had a neutral effect, while cefodizime partially restored the CsA suppressed reaction. Co-trimoxazole depressed the phagocytic response, imipenem had a neutral effect, whereas cefodizime restored the experimentally induced immunosuppression.

Disturbed host defense in peritoneal cavity during CAPD: characterization of responsible factors in dwell fluid.

In this study, the factors in overnight dwell fluid (8 to 10 hr dwell) depressing granulocyte (GC) NAD(P)H-oxidase dependent radical species production are characterized. At present, most studies have essentially focused on fresh, unspent dialysate and on peritoneal macrophages. The response to Staphylococcus aureus (Staph A) was dose-dependently depressed for both GC CO2 production (from 91.3 +/- 8.4 to 9.0 +/- 1.5 dpm/10(3) GC, P < 0.01) and chemiluminescence (CL) (peak from 7.3 +/- 0.8 to 1.6 +/- 0.8 cps x 10(3)/GC, P < 0.01). Stimulation with formyl-methionine-leucine-phenylalanine (f-MLP), phorbol myristic acid (PMA), Staphylococcus epidermidis (Staph Epi), E. coli, latex and zymosan revealed a parallel depression, pointing to an intrinsic metabolic defect, rather than failure of particle ingestion. The addition of glucose to the normal cell medium to obtain the same concentration as in the CAPD effluent (2.9 +/- 0.3 mg/dl) depressed function but not to the same extent as the genuine PD effluent. Opsonization of Staph A and E. coli induced a partial correction. No effect of pH or osmolality was observed. HPLC fractionation of CAPD effluent on a polarity based gradient revealed an elution of depressive factors in hydrophobic fractions with a nadir in F7 and F12. Analysis of the elution pattern of various uremic solutes revealed elution in F12 of p-cresol, a solute with known inhibitory effect on GC function. These events may be related to recent peritonitis (CL in response to Staph A 0.3 +/- 0.1 in effluent of 6 patients with recent peritonitis versus 2.6 +/- 0.8 cps x 10(3)/GC in 12 patients without recent peritonitis (P < 0.01). We conclude that the GC response is depressed in the presence of CAPD effluent due to excess glucose, lack of opsonization, and uremic solutes of which p-cresol is one of the responsible compounds.

Leukocyte CD14 and CD45 expression during hemodialysis: polysulfone versus cuprophane.

The expression of CD14 on monocytes and CD45 on monocytes and granulocytes was evaluated during hemodialysis by flow cytometric analysis in the 'resting state' and after in vitro stimulation with phorbol myristate acetate (PMA). A comparison of complement activating cuprophane (CU) versus less complement activating polysulfone (PS) was undertaken. 'Resting state' CD45 expression on granulocytes increased markedly during CU dialysis compared to time 0, whereas this rise was only moderate with PS (CU vs. PS, p < 0.01). When considering the increase in expression upon PMA stimulation, a lower value was obtained during CU dialysis for both CD14 (monocytes at 60 and 240 min) and for CD45 (monocytes and granulocytes at 15 min). In conclusion, granulocytes in the 'resting state' expressed more CD45 on their cell membranes during CU dialysis, whereas CD14 and CD45 upregulation after ex vivo addition of PMA was blunted during CU dialysis.

Mechanisms of uremic inhibition of phagocyte reactive species production: characterization of the role of p-cresol.

It is generally recognized that the uremic syndrome results in a depression of immune function, but the uremic solutes responsible remain largely unidentified. In this study, the effect of 18 known uremic retention solutes, including urea and creatinine, on hexose monophosphate shunt (HMS)-dependent glucose-1-C14 utilization (G1C-U), chemiluminescence production (CL-P) and flow cytometric parameters (FCP) of respiratory burst and phagocytosis were evaluated in granulocytes and/or monocytes. Among the compounds studied, only p-cresol depressed whole blood respiratory burst reactivity (G1C-U, CL-P) dose dependently at concentrations currently encountered in end-stage renal disease (ESRD) (P < 0.05 from 5 micrograms/ml on). The effect of p-cresol was enhanced by increasing incubation times from 10 to 120 minutes. HMS activity of isolated packed erythrocytes remained unaffected. FCP of respiratory burst activity (Bursttest, expressed as log fluorescence units, LFU) revealed a marked depression in the presence of p-cresol (from 700 +/- 167 to 291 +/- 128 LFU for granulocytes, from 278 +/- 102 to 146 +/- 52 LFU for monocytes, P < 0.01), whereas particle ingestion (Phagotest) remained unaffected. Cell-free myeloperoxidase activity was also markedly depressed in the presence of p-cresol. Polarity based HPLC-elution of a standard solution containing all the solutes studied, using a gradient from 100% formic acid to 100% methanol during 60 minutes, revealed elution of p-cresol after 46.6 minutes, pointing to its relative hydrophobicity. Conjugation of p-cresol to p-cresylsulfate anihilated the depressive effect of p-cresol on granulocyte function, and at the same time caused a shift in HPLC-elution pattern to a less lipophilic range.(ABSTRACT TRUNCATED AT 250 WORDS)

Uraemic toxic retention solutes depress polymorphonuclear response to phagocytosis.

Previous studies from our laboratory have demonstrated that the activity of the hexose monophosphate shunt (HMS) pathway in phagocytosis-related respiratory burst is disturbed in end-stage renal disease. To determine whether uraemic solute retention is responsible for this defect the HMS-path was evaluated by measurements of glucose-1-C14 utilization and determination of 14CO2 production in polymorphonuclear cells (PMNLs), suspended in normal plasma or uraemic biological fluids. Normal PMNLs, while suspended in normal or uraemic plasma, were stimulated with either latex, zymosan or Staph. aureus; CO2 generation (measured as DPM/10(3) PMNL, normal versus uraemic plasma) was depressed in uraemic plasma in response to latex (from 43 +/- 5 to 20 +/- 3), zymosan (from 72 +/- 8 to 47 +/- 4) (P < 0.01), and Staph aureus (from 73 +/- 17 to 47 +/- 8 DPM/10(3) PMNL) (P < 0.05). The degree of inhibition was similar for each stimulus. To characterize the substances responsible for this defect we fractionated uraemic plasma ultrafiltrate by polarity-based semipreparative C18 reversed phase HPLC and found a decreased response to Staph. aureus in the presence of fraction 2 (from 102 +/- 13 to 23 +/- 10 DPM/10(3) PMNL, P < 0.05), and in fractions 8 and 11 (lowest value in fraction 8, 54 +/- 14 DPM/10(3) PMNL, P < 0.05 versus control). The pattern of HPLC elution on a gradient from 100% formiate (pH 4.0) to 100% methanol indicates that there are at least two chemically distinguishable groups of compounds, one hydrophilic (in fraction 2), and one lipophilic (in fractions 8 and 11). We conclude that uraemic biological fluids contain factors that inhibit HMS activity related to phagocytosis, and that at least two groups of components with different characteristics are involved.

Antibiotics and energy delivery to the phagocytosis-associated respiratory burst in chronic hemodialysis patients: a comparison of cefodizime and cotrimoxazole.

Twenty-three stabilized chronic uremic patients with no active or recent infection were treated for 10 days with either cefodizime (5 x 2 g intravenously, n = 10) or cotrimoxazole (960 mg orally b.i.d., n = 8) in order to evaluate the effects on the depressed polymorphonuclear metabolic response to phagocytic challenge; a separate group of 5 patients received placebo. Ex vivo evaluation in whole blood of energy delivery to the phagocytosis-associated respiratory burst activity in response to latex and zymosan challenge was determined by measuring hexose-monophosphate shunt NAD(P)H-oxidase-related glycolytic activity. Cefodizime induced a statistically significant increase in the baseline-depressed glycolytic response for both latex and zymosan challenge, in contrast to cotrimoxazole and placebo. Depressed phagocytosis-related metabolic function in hemodialyzed patients was stimulated by cefodizime in recommended therapeutic doses but not by cotrimoxazole, the effect persisting for at least 2 weeks after the end of treatment.

Phagocyte metabolic activity during hemodialysis with different dialyzers not affecting the number of circulating phagocytes.

Overall leukocyte counts decrease during certain forms of hemodialysis, but little information is available on the intradialytic evolution of phagocytic metabolic function, especially during dialysis with dialyzers not affecting the number of circulating phagocytes. This study evaluated the phagocytic capacity of granulocytes and monocytes to generate CO2 out of glucose under basic unchallenged conditions and after stimulation with latex or zymosan, before and after 15, 60 and 240 minutes of dialysis with reused cuprophan, AN69S, polysulphone, polymethylmethacrylate and hemophan hemodialyzers. Phagocytic metabolic function was assessed in whole blood on the basis of 14CO2-production from labelled glucose during the phagocytic process. There were no changes in basic unchallenged CO2-production with any of the dialyzers. Reactivity to latex and zymosan, expressed per number of phagocytes, showed no decrease, irrespective of the membrane type. For polymethylmethacrylate and reused cuprophan, a slight but significant increase in metabolic reactivity was observed in response to latex and zymosan. The test employed may give a screening picture of the phagocytic reaction to contact with dialyzers and membranes and thus of their degree of biocompatibility towards the phagocyte system.

Effect of a serotonin blocking agent on renal hemodynamics in the normal rat.

These studies were designed to explore the effects of ketanserin (K), a serotonergic S2-receptor blocker on glomerular filtration rate (GFR), renal plasma flow (RPF) and autoregulation of renal blood flow (RBF) in the normal, anesthetized rat. Two doses of ketanserin were used: a high dose that, in addition to its serotonin blocking effect, possessed alpha 1-adrenergic blocking capacities; and a low dose that acted only as a serotonin S2 blocking agent. The effects of the high dose were compared to the effects of phenotolamine. Both the high dose of K and phentolamine resulted in a similar fall of systemic blood pressure from 117 +/- 4 to 78 +/- 3 and from 121 +/- 4.5 to 76 +/- 5 mm Hg, respectively (P less than 0.01). Despite this fall, GFR and RPF remained unchanged from 2.36 +/- 0.16 +/- to 2.26 +/- 0.12 ml/min, and from 5.33 +/- 0.41 to 5.76 +/- 0.5 ml/min with K, while both parameters significantly decreased with phentolamine. A remarkable preservation of the autoregulation of RBF until a renal perfusion pressure (RPP) of 70 to 75 mm Hg was noted with K, but not with phentolamine or Ringer infusion. With the low dose of K, a significant rise in GFR and PAH clearance was noted, from 2.12 +/- 0.17 to 2.59 +/- 0.18 and from 4.81 +/- 0.35 to 5.66 +/- 0.48 ml/min, respectively (P less than 0.05). A similar preservation of autoregulation of RBF was observed. Our studies suggest that in the pressure ranges below normal autoregulation of RBF in the rat, serotonin blockade is associated with maintenance of both GFR and RBF.

Relationship between phagocyte metabolic function and years of maintenance dialysis.

An index of the activation of NADPH-oxidase in the production of free radicals is CO2 production by the hexose monophosphate shunt of polymorphonuclear cells (PMN). 14CO2 production from glucose-1-C14 was studied as an indicator of PMN function after addition of latex or zymosan to predialysis whole blood, and correlated with the years spent on hemodialysis. In a series of 49 patients, a nadir in PMN metabolic activity, when compared with healthy controls, was reached in a subgroup treated for less than 24 months (n = 24, latex: 109.5 +/- 10.1 vs. 233.7 +/- 11.8; zymosan: 181.9 +/- 18.9 vs. 407.8 +/- 19.3 DPM/10(3) PMNs; p less than 0.01). In patients treated by dialysis for longer than 24 months, PMN metabolic function was significantly better, resulting in partial correction of the defect for both latex and zymosan. Phagocyte CO2 production in response to latex or zymosan correlated significantly with years of dialysis treatment (r = 0.63 and 0.56, respectively, n = 49; p less than 0.001). These findings may have implications for phagocyte reactivity towards infection, bioincompatible dialyzer membranes, and renal transplantation.

Evaluation of renal function before and after intravenous injection of non-cholangiographic water soluble contrast media in rats: preliminary results.

In this preliminary study, water soluble contrast media (CM) were administrated to normal laboratory rats (n = 11) and renal function was monitored before and followed after this challenge. A significant decrease (p less than or equal to 0.001) of the absolute urinary creatinine output, was noted during 3 days after the injection of the CM: the median (M) control value was 0.0313 mumol/min. 100 g body weight (BW) (interquartile range (IR): 0.0014) while the M values the first, the second and the third day were 0.0209 mumol/min. 100 g BW (IR: 0.0141), 0.0198 mumol/min. 100 g BW (IR: 0.0044) and 0.0265 mumol/min. 100 g BW (IR: 0.0054) respectively. The serum creatinine 24 hours after injection was 59,8 mumol/l (IR: 7.92) which is significantly higher (p less than or equal to 0.002) compared to the M serum creatinine of 51.9 mumol/l (IR: 15.0) evaluated in a group of normal unchallenged laboratory rats. These changes are in contrast with the low frequency of renal failure episodes encountered in clinical circumstances. Further experiments with inclusion of a control group receiving a sham injection seem necessary.