Influence of convection on small molecule clearances in online hemodiafiltration.

BACKGROUND: Dialysis efficacy is mostly influenced by dialyzer clearance. Urea clearance may be estimated in vitro by total ion clearance, which can be obtained by conductivity measurements. We have previously used this approach to assess in vitro clearances in a system mimicking predilutional and postdilutional online hemodiafiltration with a wide range of QD, QB, and ultrafiltration rates. Our current study elaborates on a formula that allows the prediction of the influence of ultrafiltration on small molecule clearances, and validates the mathematical approach both experimentally in vitro and clinically in vivo data. METHODS: Two conductivimeters in the dialysate side of an E-2008 Fresenius machine were used. HF80 and HF40 polysulfone dialyzers were used; reverse osmosis water and dialysate were used for blood and dialysate compartments, respectively. Study conditions included QB of 300 and 400 mL/min and QD of 500 and 590 mL/min, with a range of ultrafiltration rate from 0 to 400 mL/min in postdilutional hemodiafiltration and to 590 mL/min in predilutional hemodiafiltration. Urea clearances were determined in the in vivo studies, which included 0, 50, 100, and 150 mL/min ultrafiltration rates. RESULTS: The ultrafiltration rate and clearance were significantly correlated (R > 0.9, P < 0.001) and fitted a linear model (P < 0.001) in all of the experimental conditions. The following formula fitted the experimental points with an error <2% for both postdilutional and predilutional online diafiltration in vitro, respectively. K = K0 + [(QB - K0)/(QB)] x ultrafiltration rateK = K0 + [((QD x QB)/(QB + QD) - K0)/QD] x ultrafiltration rate where K is the clearance; K0 is the clearance with nil ultrafiltration rate; QD is the total dialysate produced (in commercial HDF, QD = QDi + Qinf). Since weight loss was maintained at 0, ultrafiltration rate = infusion flow. QB is the "blood" line flow. The formula was also verified in vivo in clinical postdilutional hemodiafiltration with a QB taking into account the cellular and water compartments. DISCUSSION: In vitro, by simply determining the clearance in conventional dialysis, the total clearance for any ultrafiltration rate may be estimated in both predilutional and postdilutional online diafiltration with an error of less than 2%. The same applies to in vivo postdilutional hemodiafiltration when the formula takes into account the cellular and water composition of blood.

Precise quantification of dialysis using continuous sampling of spent dialysate and total dialysate volume measurement.

The "gold standard" method to evaluate the mass balances achieved during dialysis for a given solute remains total dialysate collection (TDC). However, since handling over 100 liter volumes is unfeasible in our current dialysis units, alternative methods have been proposed, including urea kinetic modeling, partial dialysate collection (PDC) and more recently, monitoring of dialysate urea by on-line devices. Concerned by the complexity and costs generated by these devices, we aimed to adapt the simple "gold standard" TDC method to clinical practice by diminishing the total volumes to be handled. We describe a new system based on partial dialysate collection, the continuous spent sampling of dialysate (CSSD), and present its technical validation. Further, and for the first time, we report a long-term assessment of dialysis dosage in a dialysis clinic using both the classical PDC and the new CSSD system in a group of six stable dialysis patients who were followed for a period of three years. For the CSSD technique, spent dialysate was continuously sampled by a reversed automatic infusion pump at a rate of 10 ml/hr. The piston was automatically driven by the dialysis machine: switched on when dialysis started, off when dialysis terminated and held during the by pass periods. At the same time the number of production cycles of dialysate was monitored and the total volume of dialysate was calculated by multiplying the volume of the production chamber by the number of cycles. Urea and creatinine concentrations were measured in the syringe and the masses were obtained by multiplying this concentration by the total volume. CSSD and TDC were simultaneously performed in 20 dialysis sessions. The total mass of urea removed was calculated as 58038 and 60442 mmol/session (CSSD and TDC respectively; 3.1 +/- 1.2% variation; r = 0.99; y = 0.92x -28.9; P < 0.001). The total mass of creatinine removed was 146,941,143 and 150,071,195 mumol/session (2.2 +/- 0.9% variation; r = 0.99; y = 0.99x + 263; P < 0.001). To determine the long-term clinical use of PDC and CSSD, all the dialysis sessions monitored during three consecutive summers with PDC (during 1993 and 1994) and with CSSD (1995) in six stable dialysis patients were included. The clinical study comparing PDC and CSSD showed similar urea removal: 510 +/- 59 during the first year with PDC and 516 +/- 46 mmol/dialysis session during the third year, using CSSD. Protein catabolic rate (PCR) could be calculated from total urea removal and was 1.05 +/- 0.11 and 1.05 +/- 0.09 g/kg/day with PDC and CSSD for the same periods. PCR values were clearly more stable when calculated from the daily dialysate collections than when obtained with urea kinetic modeling performed once monthly. We found that CSSD is a simple and accurate method to monitor mass balances of urea or any other solute of clinical interest. With CSSD, dialysis efficacy can be monitored at every dialysis session without the need for bleeding a patient. As it is external to the dialysis machine, it can be attached to any type of machine with a very low cost. The sample of dialysate is easy to handle, since it is already taken in a syringe that is sent directly to the laboratory. The CSSD system is currently in routine use in our unit and has demonstrated its feasibility, low cost and high clinical interest in monitoring dialysis patients.

[Detection of liver metastases from digestive cancer. Value of alkaline phosphatases, their macromolecular isoenzyme and of ceruloplasmin]. / Détection de métastases hépatiques d'un cancer digestif--intérêt des phosphatases alcalines, de leur isoenzyme macromoléculaire et de la céruléoplasmine.

In order to improve the non aggressive diagnosis of hepatic metastasis from digestive neoplasm, the authors analyzed the following biological parameters: aminotransferases, alkaline phosphatase and lacticodehydrogenase isoenzymes, gammaglutamyl-transpeptidase, conjugated and total bilirubin, C-reactive protein, type A, G, M immunoglobulins, C3 complement factor, alpha-1 acidic glycoprotein (orosomucoid), haptoglobin, ceruloplasmin, transferrin, albumin, prealbumin, ferritin. This work included 54 patients with digestive tract cancer (esophageal, gastric, colic, rectal, anal localizations), divided in two groups: M- (n = 27), without hepatic metastasis), and M+ (n = 27, with histological confirmed hepatic metastasis). The Mann-Whitney test showed significant differences for 12 parameters between the 2 groups. With more than 60% sensitivity (Se) and specificity (Sp), according to the ROC curves, the following parameters can be selected: Total alkaline phosphatase (Se 89%, Sp 70%) and their macromolecular H2 fraction, lacticodehydrogenase fraction 4 (Se 63%, Sp 63%), gammaglutamyl-transpeptidase (Se 85%, Sp 82%), ceruloplasmin (Se 64%, Sp 65%), aspartate-aminotransferase determination (Se 63%, Sp 65%).

Treatment with vigabatrin may mimic alpha-aminoadipic aciduria.

PURPOSE: We describe a secondary effect of treatment with vigabatrin (VGB). A significant increase in alpha-aminoadipic acid (AAA) occurred in plasma and urine of VGB-treated children, thus mimicking a known rare metabolic disease, alpha-aminoadipic aciduria (AAAuria). METHODS: We studied eight children, aged from 3 months to 5 years, who were receiving VGB for drug-resistant partial epilepsies. Plasma and urine amino acids were assayed with ninhydrin detection on an automated Beckman 6300 analyzer. RESULTS: In eight out of eight children, there was a significant increase of AAA in plasma and in urine. Plasma values ranged from 7 to 8 microM (control values, < 5) and urinary values from 67 to 274 mmol/mol creatinine (control values, < 25). CONCLUSIONS: The concentrations of AAA in these VGB-treated children were as high as the concentrations found in the inherited metabolic disease, AAAuria. This could lead to incorrect diagnosis and to inappropriate genetic counseling. Thus whenever a genetic metabolic disease is suspected, amino acid chromatography testing should be performed before initiation of treatment with VGB.

Major hyperpipecolataemia in a normal adult.

We describe the fortuitous discovery of a 44-year-old man with a very high hyperpipecolataemia (250 mumol/L; normal < 2.5). This patient has none of the clinical features seen in peroxisomal diseases, he is a strictly normal intelligent adult. A stereochemical study of this pipecolic acid was performed using D-amino acid oxidase, and identified it as L-pipecolic acid. We suggest that isolated L-hyperpipecolataemia may be a benign trait.

[Assessment of musculoskeletal disorders using a questionnaire]. / Erfassung muskuloskeletaler Beschwerden mittels Fragebogen.

The standardized illustrated questionnaire on musculoskeletal disorders of the Japanese Committee on Occupational Cervico-branchial Disorders was translated into German. This questionnaire, composed of 37 items about the occurrence (never/seldom, occasionally, almost daily) of symptoms (pain, stiffness, fatigue) in twelve body regions, was used together with medical examinations (pressure points), and further information was gathered on the consumption of analgetics and medical visits prompted by musculoskeletal symptoms. The questionnaire's reliability and validity were tested in 644 persons from twelve occupational groups within the service sector. Factor analysis showed that symptoms can be grouped into four distinct regions of occurrence: neck/shoulder/area, back/low back, and both left and right upper extremities. Indices based on these regions are consistent (Cronbach alpha approximately 0.8). Palpation findings steadily increase with increasing index values. The consumption of medicaments and medical visits positively correlate with the indices. Consequently the questionnaire is judged to be a valid instrument for studying musculoskeletal disorders at the workplace.

High levels of c-fos proto-oncogene expression in normal human adult skin.

The proto-oncogene c-fos is thought to play an important role in the modulation of cell growth and differentiation. In normal tissues that have been studied to date, c-fos expression has been found to be regulated in a tissue-specific manner. Actually, little is known about its expression in normal human adult skin (NHAS). Moreover, the epidermis is a useful tissue to study the role of cellular oncogenes because keratinocytes can be observed simultaneously in their proliferative as well as differentiated state. We studied c-fos expression in NHAS using different molecular approaches which permit us to characterize and localize c-fos products within the epidermis, specifically, at the RNA level by Northern blot and in situ hybridization, and at the protein level by immunofluorescence and Western blotting. Here, we show that both c-fos mRNA and protein are present at high levels in NHAS. These results contrast with the low level of c-fos expression reported for most human adult tissues. Furthermore, c-fos expression is visible throughout the epidermal layers indicating that it is not restricted to proliferating basal cells. The epidermis, therefore, represents the first human adult tissue where c-fos is expressed at high levels in vivo and provides an interesting model to further elucidate the role of this proto-oncogene in normal and pathologic conditions.

Inhibitory effect of the C-terminal octapeptide of oxyntomodulin on pentagastrin-stimulated gastric acid secretion in man.

The effect of the C-terminal octapeptide of human oxyntomodulin (KA-8) on pentagastrin-stimulated gastric acid secretion was studied versus placebo in eight human volunteers after an overnight fast, using a double-blind randomized protocol. KA-8 (7.5 nmol/kg body weight) was bolus-injected at a plateau stimulation obtained with pentagastrin (3 micrograms/kg/h). KA-8 significantly decreased the volume secreted by 36% (p less than 0.025) and the acid output by 32% (p less than 0.025) 20 min after injection. The areas under the curve were significantly reduced for volume and acid output during the 1st h after peptide injection.

[Health care needs, brain functional ability, social behavior and social attendant circumstances of elderly patients in community and institutionalized geriatric care in the city of Zurich]. / Pflegebedürftigkeit, Hirnleistungs-fähigkeit, Sozialverhalten und soziale Begleitumstände von Alterspatienten in der offenen und institutionalisierten Alterspflege in der Stadt Zürich.

All aged persons being helped by community nursing-services, the house-helper service, the housekeeper service, or living in a home for the aged or in an apartment for seniors in a representative area of the city of Zurich are compared to all patients in nursing-homes of the city. This study included the size of social network measured by the number of different regular visitors, the number of different medications taken daily, the cognitive abilities measured by the Mini Mental Status, the activities of daily living and the social skills rated by the care-givers as well as the intensity of the care given. The groups were similar in age and sex-distribution but the nursing-home patients differed significantly in all other parameters from the others. In contrast, no significant differences could be found between persons receiving care in their homes and those in institutions for the aged.

[Cytometric analysis of the DNA content of the thymus, spleen and liver in C57BL/6 mice]. / Analyse cytométrique du contenu en ADN du thymus, de la rate et du foie de la souris C 57 BL/6.

Flow cytometric analysis of cell DNA content in the mouse C 57 BL/6 shows better results with fine needle aspiration than with mechanical dissociation of the tissues. There is no difference fresh and deep frozen stored tissues. In the liver, it has been found two cell populations with different DNA content including diploid and tetraploid cell lines. In the spleen and the thymus, only diploid cells are encountered with different cell cycles belonging to the organ.

[Aerobic capacity estimated from heart rate under submaximal load: an indicator of complaints, personality, personal activity and social status]. / Geschätztes Sauerstoffaufnahmevermögen aus der Herzfrequenz bei submaximaler Belastung: ein Indikator für Beschwerden, Persönlichkeit, Eigenaktivität und Sozialstatus.

In 34 young females (mean: 21 years, range 18-30), working with VDTs, maximum aerobic capacity (MAC) was estimated by use of a cycle ergometer and Astrand's nomogram. MAC correlated with musculoskeletal complaints (-.29, p less than .05), eye complaints (-.36, p less than .05), personal activity (.38, p less than .05), personality dimensions: "Imperturbability" (.41, p less than .01), "Wellbeing" (.31, p less than .05), "Traditionalism" (-.45, p less than .01) and "Psychophysic constitution" (all evaluated by questionnaires), a body weight index (-.51, p less than .01) and systolic blood pressure after performance (-.51, p less than .01). MAC also distinguished significantly between a priori classified subgroups with seldom or frequent musculoskeletal complaints, the latter scoring higher (31 vs. 25 ml O2/kg X min), and subgroups with high or low EMG values of the trapezius muscle, measured at the workplace (25 vs. 33 ml O2/kg X min). A similarly ascertained MAC separated a comparable group of 55 young female university students (mean: 21 years, range 19 to 27) from the VDT users (38 vs. 27 ml O2/kg X min). It is concluded that the indirect estimation of MAC using Astrands nomogram is sensitive enough for certain practical uses and that MAC shows significantly plausible relations to a set of personality factors, social status, complaints and physiological variables to serve as a reliable indicator for personal fitness.

[Partial splenic resections and Nd-YAG laser]. / Résections partielles de rate et laser YAG-Nd.

Eleven partial splenectomies are performed in pigs. Simultaneous section and hemostasis are obtained with continuous 80 W power shoot. There is no hemorrhagic or septic complication and normal splenic weight is recovered in 5 months. Platelets elevation observed in post-operative. Platelets elevation observed in post-operative period returns to normal rate between 20th and 30th day. Acute cellular damage of cut splenic edge does not exceed 3 mm in thickness. Semi-thick and electron microscopic examination reveals at day 10 mitotic figures of lymphocytes (i.e. splenic regeneration) and at day 30 high density of mast cells and plasmocytes i.e. cellular biostimulation).

[Hepatic resections using an Nd YAG laser. Anatomic and biological results of an experimental study]. / Résections hépatiques au laser YAG Nd. Résultats anatomiques et biologiques d'une étude expérimentale.

Experimental hepatic resections were performed with a Nd YAG laser in 32 New-Zealand rabbits. The beam was simply transmitted by a quartz fiber of 4 degrees 2 and 8 degrees in divergence for the full angle, without any focalization. Section was possible at a power output superior to 20 W requiring short cutting time. Complete hemostasis was obtained as long as the diameter of encountered vessels did not exceed 4,5 mm. Immediately after resection the parenchyma was covered by an ischemic layer varying from 2 to 8 mm. Its thickness rapidly increased to high levels whenever the power output exceeded 40 W or when hepatic pedicle was clamped. Healing process was installed at day 30. There was no hemorrhagic, biliary or septic complication. Eleven animals were alive eight months after. Histological examination revealed four layers: a first one of carbonization, a second of condensed cells, a third of edema presenting disruption of sinusoids, and a fourth one composed of progressively normal tissue. Peripherical veins presented thrombosis of their blood content and coagulative necrosis of their wall while bile canaliculi were preserved. Fibrosis appeared in the edematous layer the 10th day and was completely formed at day 30. Electron microscopic examination revealed shadowy cells embedded in the condensed layer and mitochondrial alteration in the edematous layer. The 15th day foci of cell regenerations were registered. High levels of SGOT, SGPT and LDH (fractions IV and V) were observed immediately after resection.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatic resection with an Nd:YAG laser in pig.

Eleven hepatic resections were performed by means of a divergent Nd:YAG laser. The beam was transmitted through a fiberoptic delivery system without any handpiece. The shortest resection time and most limited ischemic damage (4 mm) were obtained with 80-W power shoots and a low divergent beam (4 degrees 2 for full angle). The hemostatic effects of the Nd:YAG controlled bleeding from veins of up to 4.5 mm in diameter, and parenchymatic oozing from the cut edge minimized blood loss. Histological examination revealed the importance of cellular deterioration in the ischemic layer, while electron microscopy showed selective destruction of cell organelles and protein denaturation. Marked elevation of hepatic serum enzymes suggests a high degree of cellular damage. Postoperative examinations confirmed an uncomplicated healing process. Finally, the use of a flexible fiberoptic enables easy surgical manipulation.