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Peri-operative filtration of disseminated cytokeratin positive cells in patients with colorectal liver metastasis.

BACKGROUND: Liver resection is the only potential cure for patients with colorectal liver metastasis. However, more than 30% of patients will develop tumour recurrence, probably caused by tumour cells disseminated before or during surgery. As prevention of cell dissemination is barely obtainable, alternative concepts have to be discussed. METHODS: The potential of leukocyte adhesion filters for the removal of cytokeratin positive cells (CK+) from blood was studied in 18 patients undergoing liver resection for colorectal liver metastasis. Blood sampling was done via a liver venous catheter during hepatic mobilisation. Filtration was done with an in-line WBF2 filter system. To define the relation between surgery and cell release we compared patients' pre-operative and intra-operative blood and bone marrow (BM) samples with their CK expression using immunochemical staining. RESULTS: CK+ cells were detected in BM samples of nine of 14 patients before surgery, indicating early dissemination. In ten of 18 patients CK+ cells were detected in blood samples during hepatic mobilisation; all ten patients underwent major liver surgery (R0 resection). In those patients recurrent disease was observed more often (P < or = 0.05). In 17 of 18 patients CK+ cells were not detectable after filtration procedure, which indicated cell adhesion to the filter medium. CONCLUSION: Liver resection due to metastasis leads to frequent intra-operative tumour cell shedding. As the detection of CK+ cells is correlated with disease recurrence, modification of surgical techniques to prevent cell dissemination, and additional therapeutic concepts such as advanced filtration technology, have to be discussed.

Bone Marrow↗

Determinants of the initial effects of captopril on blood pressure, glomerular filtration rate, and natriuresis in mild-to-moderate chronic congestive heart failure secondary to coronary artery disease.

Whereas angiotensin-converting enzyme inhibitors are now indicated for all grades of chronic heart failure, the 2 adverse effects that limit use of these drugs are systemic hypotension and renal dysfunction. The recognized clinical correlates such as hyponatremia and high diuretic dose, which predict occurrence of these adverse effects in severe chronic congestive heart failure (CHF), are rarely evident in patients with mild-to-moderate CHF. Accordingly, we studied 36 patients with stable, moderate CHF in a double-blind, placebo-controlled, crossover fashion to evaluate by multiple discriminate regression analysis the pathophysiologic determinants of changes in blood pressure, glomerular filtration rate, and urinary sodium excretion after initial converting enzyme inhibition with captopril 25 mg. A captopril-mediated decrease in mean arterial pressure was predicted by 3 factors (r2 = 0.74): the decrease in serum angiotensin II (F ratio = 10.3, p < 0.01), the decrease in plasma norepinephrine (F = 8, p = 0.02), and, inversely by pretreatment mean arterial pressure (F = 5.6, p = 0.04), patients with higher initial values exhibiting greater decreases in response to captopril. A captopril-mediated decline in glomerular filtration rate, determined by radioisotope elimination, was also predicted by 3 factors (r2 = 0.67): a decrease in renal plasma flow (F = 48.6, p < 0.01), low pretreatment glomerular filtration rate (F = 11.1, p < 0.01), and low absolute post-treatment serum angiotensin II (F = 5, p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Regulation of renal hemodynamics and glomerular filtration in patients with renovascular hypertension during converting enzyme inhibition with captopril.

Changes in regional hemodynamics and function of the kidney during inhibition of angiotensin converting enzyme were studied in 25 patients with renovascular hypertension. A variety of patterns were observed depending upon (1) the activity of the renin-angiotensin system and concomitant administration of diuretics, and (2) the presence of bilateral renal artery stenosis. Increase in blood flow, glomerular filtration rate and sodium excretion during angiotensin blockade, in some instances, indicated tonic renal vasoconstriction before therapy. Release of the kidney from these effects may explain, in part, the sustained effectiveness of converting enzyme inhibition in chronic congestive heart failure. When compared with blood pressure reduction due to nitroprusside administration, initial captopril therapy in patients with unilateral stenosis produced a selective decrease in glomerular filtration, despite well-preserved renal blood flow. These results confirm the importance of efferent arteriolar vasoconstriction due to angiotensin II in man. Experimental studies demonstrate that angiotensin may become critical to sustaining glomerular filtration rate in the presence of stenosis during vasodilation. In patients with bilateral stenosis, this effect produces a syndrome of functional renal insufficiency. Taken together, these data demonstrate an intrarenal action of angiotensin II in human renovascular hypertension and underscore the importance of evaluating the functional impact of changes in regional hemodynamics.

Adult↗

Comparison of filtration and equilibrium dialysis methods for [3H]imipramine binding to human platelets.

Receptor binding of imipramine in human platelets was assessed by filtration through glass-fiber filters and by equilibrium dialysis. Both methods yield drug-receptor dissociation constants of similar magnitude (10(-9) M) to literature values. However, the density of binding sites (Bmax) was fivefold lower by filtration (473 +/- 92 fmol/mg protein) compared to equilibrium dialysis (2652 +/- 765 fmol/mg protein). Dialysis allows direct assessment of free imipramine and avoids drug loss during the separation step of the filtration assay. Additional advantages were found for computer nonlinear regression analysis of untransformed data to eliminate errors owing to linear transformation in the Scatchard analysis and for simultaneous quantitation of nonspecific and total drug binding.

Blood Platelets↗

The filtration characteristics of the aqueous outflow system.

To determine the filtration characteristics of the aqueous outflow system, microspheres (0.18 micron -1.1 micron) were perfused through enucleated human and bovine eyes. The microspheres were smaller than morphologically determined flow dimensions, and yet a significant fraction of all sizes of microspheres were captured. The bovine (calf) aqueous outflow system was found to be a far more efficient filter than was the human outflow system. Combining the experimental results with morphological observations and theoretical calculations leads to the conclusion that 'sticky wall' interactions are responsible for much of the microsphere capture, and that the site of filtration may be distinct from the site of flow resistance. Consequently, the dimension of the sites generating flow resistance cannot be determined from filtration studies.

Animals↗

Apheretic treatment of severe familial hypercholesterolemia: comparison of dextran sulfate cellulose and double membrane filtration methods for low density lipoprotein removal.

The two more widely available techniques for the extracorporeal removal of low density lipoproteins (LDL), dextran sulfate cellulose column and double membrane filtration, were comparatively tested in severe familial hypercholesterolemic patients, both acutely and during a continued 3-month treatment. The selective dextran sulfate procedure removed close to 60% of LDL and 16% of high density lipoproteins (HDL) upon each apheresis, vs. 42% and 32%, respectively, in the case of the semi-selective double membrane filtration. Upon long term biweekly treatments, LDL-cholesterol (LDL-C) decreased, with the selective procedure, from a pre-treatment level of 406.0 +/- 40.7 mg/dl to a value fluctuating between 295.4 +/- 33.8 mg/dl and 116.9 +/- 22.0 mg/dl (highest vs. lowest levels) whereas, in the case of double membrane filtration, LDL-C levels ranged between 334.8 +/- 39.8 mg/dl and 192.3 +/- 49.9 mg/dl. HDL-cholesterol levels were somewhat raised, to a higher extent with dextran sulfate apheresis. The LDL/HDL-cholesterol "atherogenic ratio", decreased from a pre-treatment value of 10.27 +/- 3.04 to values ranging between 3.61 and 6.82 with dextran sulfate and between 6.70 and 7.68 with double membrane plasmapheresis.

Adult↗

Isolation of human T lymphocytes: comparison between nylon wool filtration and rosetting with neuraminidase (VCN) and 2-aminoethylisothiouronium bromide (AET)-treated sheep red blood cells (SRBC).

Isolation of human T lymphocytes by rosetting with SRBC, centrifugation on Ficoll-Hypaque gradients and lysis of SRBC, which reportedly affects the functional activities of lymphocytes, was compared to isolation of T lymphocytes by filtration through a nylon wool column. The two methods were similar in yields and purity of T lymphocytes. No selective loss of T cell subpopulations was found in T lymphocytes isolated by filtration through a nylon wool column as judged by the percentage of T gamma and T micron and the suppressor and helper activity in functional assays. Therefore, filtration through a nylon wool column is a useful method to purify T lymphocytes and has the advantage of being comparatively simple and quick to perform and of avoiding manipulations which may affect the functional activity of T lymphocytes.

Animals↗

A glass-fiber filtration assay for solution phase hapten-antibody binding. Effect of surface treatment with a polycation.

Radioligands bound to murine monoclonal and polyclonal antibodies in solution are rapidly and effectively separated from free ligand by filtration through either untreated or polyethylenimine (PEI)-pretreated glass-fiber filters. Ligand binding to selected anti-morphine monoclonal antibodies, determined by filtration through untreated filters, was significantly greater (1.5-3.0-fold) than the binding activities obtained by gel filtration. However, radioactivity retained by filters that were pretreated with PEI (pH 4) was essentially the same as that obtained using the Sephadex G-25 short-column assay. The pH dependence of the retention on the coated fibers suggests that the mechanism of binding of antibodies to glass is different from that to the PEI-treated surfaces. The quantitative aspects of the assay are reported. The method should prove useful where quantitative, rapid and inexpensive binding radioassays need to be performed.

Antibodies, Monoclonal↗

A proposal for purification of salivary polymorphonuclear leukocytes by combination of nylon mesh filtration and density-gradient method: a validation by superoxide- and cyclic AMP-generating responses.

Isolation and purification of salivary polymorphonuclear leukocytes (SPMNs) from accompanying epithelial cells was presented by using a density-gradient method with Ficoll. SPMNs samples prepared by already established methods (nylon mesh filtration) was compared with SPMNs samples after further purification by Ficoll (d = 1.083). Microscopically, SPMNs samples after nylon mesh filtration contain higher percentage of epithelial cells than SPMNs samples after Ficoll centrifugation. In response to stimulation of superoxide generation, both samples showed the same pattern of response. However, in response to forskolin and prostaglandin E1, cyclic AMP levels in samples after nylon mesh purification were significantly higher than in samples after Ficoll purification because of the presence of contaminating epithelial cells. We can conclude that, although nylon mesh filtration is satisfactory when we need to examine superoxide generation but further purification is necessary when we want to measure factors like intracellular cyclic AMP formation.

Alprostadil↗

Vascular filtration function in galactose-fed versus diabetic rats: the role of polyol pathway activity.

These studies were undertaken to assess the effects of increased galactose (v increased glucose) metabolism via the polyol pathway on vascular filtration function in the kidneys, eyes, nerves, and aorta. Quantitative radiolabeled tracer techniques were used to assess glomerular filtration rate (GFR) and regional tissue vascular clearance of plasma 131I-bovine serum albumin (BSA) in five groups of male Sprague-Dawley rats: nondiabetic controls, streptozotocin-diabetic rats, nondiabetic rats fed a 50% galactose diet, diabetic rats treated with sorbinil (an aldose reductase inhibitor), and galactose-fed rats treated with sorbinil. Sorbinil was added to the diet to provide a daily dose of approximately .2 mmol/kg body weight. After 2 months of diabetes or galactose ingestion, albumin clearance was increased twofold to fourfold in the eye (anterior uvea, choroid, and retina), sciatic nerve, aorta, and kidney; GFR was increased approximately twofold and urinary excretion of endogenous albumin and IgG were increased approximately 10-fold. Sorbinil treatment markedly reduced or completely prevented all of these changes in galactose-fed, as well as in diabetic rats. These observations support the hypothesis that increased metabolism of glucose via the sorbitol pathway is of central importance in mediating virtually all of the early changes in vascular filtration function associated with diabetes in the kidney, as well as in the eyes, nerves, and aorta. On the other hand, renal hypertrophy in diabetic rats and polyuria, hyperphagia, and impaired weight gain in galactose-fed and in diabetic rats were unaffected by sorbinil and therefore are unlikely to be mediated by increased polyol metabolism.

Animals↗

The effects of kilovoltage and filtration on dental radiographic film sensitivity.

A sensitometric method was used to compare the effects of changing kilovoltage and filtration on the sensitivity of a dental radiographic emulsion. Five combinations were investigated: 90 kVp, 3.5 mm. aluminum filtration; 90 kVp, 2.5 mm. Al; 70 kVP, 2.5 mm. Al; 70 kVp, 1.5 mm Al; and 50 kVp, 1.5 mm. Al. Maximum emulsion sensitivity was demonstrated at 90 kVp and 3.5 mm.aluminum filtration; 90 kVp, 2.5 mm. Al and 70 kVp, 2.5 mm. Al showed slight reductions in sensitivity (4 percent and 6 percent, respectively). A progressively greater reduction in emulsion sensitivity was observed at 70 kVp, 1.5 mm. Al (10 percent) and 50 kVp, 1.5 mm. Al (26 percent). Emulsion sensitivity is one factor to be considered when one is selecting beam quality.

Evaluation Studies as Topic↗

The use of added erbium filtration in intraoral radiography.

Using D and E speed film, intraoral exposures were made of a phantom at 70 and 90 kVp, with and without erbium filtration. Measurement of surface exposures indicates substantial reduction when erbium filtration was used. However, there was a visible loss of contrast. The raters agreed that radiographs made with E speed and D speed film, both with and without erbium filtration, were all of adequate diagnostic quality. The radiographs with the highest contrast were consistently preferred by all of the raters.

Erbium↗

Effects of filtration, collimation, and target-receptor distance on artificial approximal enamel lesion detection with the use of RadioVisioGraphy.

RadioVisioGraphy is an imaging modality that uses a charge-coupled device electronic sensor. Dental charge-coupled device imaging can be used to detect dental caries; however, it was not known what effect beam collimation, added filtration, or variable target-receptor distance has on this task. The purpose of this investigation was to study these effects were imaged by conventional radiography and RadioVisioGraphy varying exposure time, target-receptor distance, collimation, and filtration. Printed RadioVisioGraphy images without enhancement and E-speed radiographs were evaluated by five viewers. The number of true-positives and false-positives were compared as were sensitivity, specificity, positive and negative predictive values, accuracy, and entrance level radiation exposure. Added filtration reduced the false-positives regardless of collimation or target-receptor distance. True-positives and false-positives were greater at a target-receptor distance of 8 inch at exposures < 0.10 seconds (F < 0.0151). E-speed radiographs had a greater specificity and positive predictive value than RadioVisioGraphy images without image enhancement; however, no significant differences were found between RadioVisioGraphy images and E-speed radiographs in true-positive or false-positive identifications without image enhancement.

Analysis of Variance↗

Effect of prostaglandin inhibition on glomerular filtration rate in normal and uremic rabbits.

Studies were performed to assess the effect of alterations in prostaglandin biosynthesis on glomerular filtration rate in rabbits with normal renal function and after surgical reduction of renal mass. In normal animals, the administration of either of two cyclo-oxygenase inhibitors resulted in a 53% reduction in urine prostaglandin E excretion, but no change in the creatinine clearance. Creatinine clearance rates were normal almost 71% lower in the uremic animals when compared to the animals with normal renal function. Despite the reduction in renal mass, urine prostaglandin E excretion rates in the uremic animals were over twice that seen in normal rabbits. When factored by either glomerular filtration rate or remaining renal mass, urine prostaglandin E excretion rates in uremic rabbits were compared to normal animals were increased more than 9-times and 40 times respectively. Administration of cyclo-oxygenase inhibitors in the uremic animals resulted in a 71% decrease in urine prostaglandin E excretion, unlike and non-uremic animals, a 53% fall in creatinine clearance. These findings suggest that intact renal prostaglandin biosynthesis is a necessary factor in the homeostatic adaptive mechanisms which maintain the glomerular filtration rate in animals with decreased renal mass.

Animals↗

A comparison between centrifugation and filtration as a means to separate bound and unbound ligand during 3[H]-spiroperidol binding.

A centrifugation method for the separation of bound and unbound ligand during 3[H]-spiroperidol binding in rat brain was compared with the more widely used filtration method. The centrifugation method yielded significantly greater total and specific binding, and lower nonspecific binding, than filtration. Assay reproducibility was also found to be superior when the centrifugation method was used as compared to the filtration binding method. Scatchard plots produced by both methods yielded comparable Kd and Bmax values that were consistent with those previously reported.

Animals↗

Centrifugation or filtration in quantitative radioreceptor assays.

In quantitative radioreceptor assays the amount of a drug present in the medium to be assayed is inversely related to the amount of receptor-bound radiolabelled ligand. Usually, separation of the bound and free fractions of radiolabelled ligand is done by filtration, in which the bound fraction can easily be collected. However, the filtration disturbs the equilibrium between bound and free fractions, which may lead to erroneous results. Because the decrease in bound radiolabelled ligand is accompanied by an increase in free labelled ligand, we decided also to measure this free fraction after separation by centrifugation and to compare these data with the filtration data. In these experiments a radioreceptor assay for anticholinergics was employed. The results indicate that both methods are compatible in precision when appropriate conditions are used whereas each method has its specific features.

Animals↗

Cisplatin nephrotoxicity: role of filtration and tubular transport of cisplatin in isolated perfused kidneys.

Isolated perfused rat kidneys were used to determine the contribution of filtration and tubular transport of cisplatin to its nephrotoxicity. Perfusion of kidneys with 0.5 mM cisplatin concomitantly reduced tubular reabsorption of electrolytes and glomerular filtration rate in a time-dependent manner. These renal functional changes were similar to those obtained following in vivo cisplatin treatment (10 mg/kg). In vitro exposure to cisplatin reduced the renal clearance of organic ions without reducing renal perfusate flow, suggesting that renal hemodynamic changes do not mediate cisplatin-induced proximal tubular dysfunction. Inhibition of organic ion transport also was observed in non-filtering perfused kidneys treated with 0.5 mM cisplatin, implying that filtration of cisplatin is not a prerequisite for induction of toxicity. These data also suggest that cisplatin transport from a basolateral site may be important in the development of acute nephrotoxicity.

Absorption↗

Effect of filtration, storage and platelet suspension media on platelet indices.

We describe a new approach for assessing filtration-induced changes in cellular indices of platelet concentrates at the beginning and the end of storage, using pairs of identical packs. The results revealed that post-filtered products did not store as well as their counterparts. Filtration did not induce any significant changes on aggregation as determined by spontaneous aggregation nor was there a disparity between leucocyte peroxidase/basophil count. We recommend filtration on day 2 which causes minimal loss of platelets and less change in the mean platelet volume.

Blood Platelets↗