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Biomedical subjects

R Vanholder

Publications and source records attributed to R Vanholder.

At least 253 records · Page 14Linked to original sources

Immunomodulating effects of antibiotics: literature review.

Antibiotics can interact directly with the immune system. This is a review of the immunomodulating effects of antibiotics. The Medline database on CD-ROM was searched for the years 1987 to 1994 using the following search string: "thesaurus explode antibiotics/all AND (thesaurus explode immune-system/drug effects OR thesaurus immune-tolerance/drug effects)." Aspects of the immune system studied were aspects of phagocyte functions: phagocytosis and killing, and chemotaxis and aspects of lymphocyte functions: lymphocyte proliferation, cytokine production, antibody production, delayed hypersensitivity and natural killer-cell activity. In order to quantify and to compare immunomodulatory properties of antibiotics we calculated an "immune index," defined as: number of positive statements--number of negative statements/total number of statements. Concerning phagocytosis, positive effects were observed for cefodizime, imipenem, cefoxitin, amphotericin B and clindamycin and negative effects for erythromycin, roxithromycin, cefotaxime, tetracycline, ampicillin and gentamicin. Clindamycin, cefoxition and imipenem induce enhancement of chemotaxis, whereas cefotazime, rifampicin and teicoplanin decrease chemotaxis. Regarding lymphocyte proliferation, cefodizime has the strongest stimulating effect, whereas tetracycline has the strongest negative effect. Except for erythromycin and amphotericin B the number of statements reported is too small to be conclusive for the interpretation of effects on cytokine production. Erythromycin and amphotericin B appear to stimulate cytokine production. As to antibody production, cefodizime has the strongest positive effect, whereas josamycin, rifampicin and tetracycline have marked negative effects. For delayed hypersensitivity and the natural killer-cell activity the number of statements is too small for any single antibiotic to be conclusive. There are three markedly immuno-enhancing antibiotics (imipenem, cefodizime and clindamycin) and eight markedly immuno-depressing antibiotics (erythromycin, roxithromycin, cefotaxime, tetracycline, rifampicin, gentamicin, teicoplanin and ampicillin).

Animals↗

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.

Anti-Bacterial Agents↗

Predialysis urea concentration is sufficient to characterize hemodialysis adequacy.

Mathematical description of urea kinetics for a week showed that, under steady state conditions (i.e., total removal equals total synthesis), any predialysis urea concentration is expressed as a linear function of specific urea generation (G/V) and of dialysis schedule timing and sessional Kt/V (product of clearance, K, and session time, t, divided by the urea distribution volume, V). It also predicts that TACurea is proportional to the predialysis concentrations. The ratio between the two depends linearly on delivered weekly dialysis dose ([wDD] = T(G/V)/TACurea, with T the number of hours in 1 week). These hypotheses have been tested by retrospectively analyzing urea kinetc modelling data that include all predialysis and post dialysis concentrations of 163 patient-weeks. All patients were anuric, and dialysis frequency was thrice weekly. Accuracy is assessed with regression analysis between database numbers and computed values. The theoretical ratio between midweek concentration and TACurea (1.43) is close to the computed ratio (1.46, r2 = 0.909). TACurea (slope = 1.002, r2 = 0.997), specific generation rate G/V as a precursor to PCRn (slope = 1.007, r2 = 0.985), and wDD (slope = 1.002, r2 = 0.909) are all accurately computed from predialysis concentrations. To aid in the determination of the ratio for the different predialysis, concentrations using wDD a nomogram is included.

Models, Theoretical↗

Intradialytic parenteral nutrition in malnourished hemodialysis patients. Review of the literature.

Malnutrition is a frequent problem of patients on intermittent hemodialysis and is associated with increased morbidity and mortality. Intradialytic parenteral nutrition (IDPN), i.e. intravenous supplementation of mixtures of glucose, amino acids and/or lipids during the hemodialysis session, is one of the therapeutic measures that are applied to correct this malnutrition. To our knowledge only few long-term clinical studies have been undertaken, evaluating the effect of intravenous calorie administration in hemodialysis. Most studies were carried out over a relatively short observation period in small study populations; in several of these studies, no measures were taken to prevent losses of nutrients in the dialysate; adequate control groups are often missing. The authors review the current available literature and conclude that IDPN might have a significant beneficial effect on the nutritional status in malnourished hemodialysis populations.

Amino Acids↗

Intradialytic parenteral nutrition in malnourished hemodialysis patients: a prospective long-term study.

BACKGROUND: Malnutrition is a frequent problem of patients on intermittent hemodialysis and substantially contributes to their morbidity and mortality. METHODS: In 26 hemodialysis patients who, despite dietary advice and oral nutritional supplements, still had malnutrition, the feasibility and effects of a specific intradialytic parenteral nutritional (IPN) regimen were evaluated during a 9-month study period. An IPN solution consisting of 250 mL glucose 50%, 250 mL lipids 20%, and 250 mL amino acids 7% was infused i.v. three times a week during the dialysis session. At the end of each dialysis session an additional volume of 250 mL amino acids was infused as a rinsing fluid. Insulin was administered i.v. before dialysis. RESULTS: Of the 26 enrolled patients, 16 completed the study. The remaining 10 patients withdrew mainly because of muscle cramps and nausea during the initiation phase of the treatment, when sodium was not present in the IPN fluid but was supplemented intermittently. In the 16 treated patients, body weight, which had decreased in the pretreatment period from 58.2+/-1.3 kg (-6 months) to 54.8+/-10.1 kg at the start of the study, increased again up to 57.1+/-10.7 kg after 9 months IPN (p < .05). Serum transferrin and prealbumin rose from 1.7+/-0.4 to 2.0+/-0.4 g/L and from 0.23+/-0.05 to 0.27+/-0.10 g/L, respectively. Bone densitometry showed an increase of tissue mass, mostly related to a rise in fat tissue. Triceps skinfold (p < .05) and arm muscle compartment of the midarm (p = .07) increased as well. No such changes were observed in the patients who withdrew from treatment. CONCLUSIONS: An i.v. hyperalimentation regimen applied to malnourished hemodialysis patients results in a rise of body weight and in a limited, but significant, change of some parameters of nutritional status. The rise in body weight is at least in part attributable to an increase of body fat, without changes in plasma lipid levels.

Aged↗

Calcium channel blockers in the prevention of end stage renal disease: a review.

Hypertension and high levels of proteinuria are independent risk factors for accelerated progression of renal failure. There is increasing evidence that strict control of both blood pressure (BP) and proteinuria are beneficial in slowing the rate of progression of chronic renal disease in diabetic as well as non-diabetic nephropathy. The angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin 2 receptor blockers (ARB) have clearly demonstrated their beneficial effect on both reduction of BP and proteinuria. The calcium channel blockers (CCB) have individual pharmacological and therapeutic properties that may vary, but as a group they are effective antihypertensive agents in patients with renal disease. Their effects on the kidney may extend beyond BP reduction alone. Current studies suggest that CCB do not worsen the progression of renal disease but may rather provide benefit when systemic BP has been tightly normalised. The non-dihydropyridine calcium channel blockers (NDHP), diltiazem and verapamil, slow the progression of type 2 diabetic nephropathy with overt proteinuria almost to a similar extent as observed with ACE-I. The dihydropyridine calcium channel blockers (DHP) have a variable effect on proteinuria. Pharmaceutical compounds, which inhibit the renin-angiotensin system (RAAS), remain the drugs of first choice in the treatment of hypertension and/or proteinuria in chronic nephropathy. However, a combination of two or more drugs is almost always required to attain sufficient BP reduction. CCB may have an advantage in combination with ACE-I and/or ARB.

Angiotensin Receptor Antagonists↗

Transplantation as a therapeutic option for diabetic nephropathy.

Diabetic nephropathy affects both type 1 and type 2 diabetic patients with a frequency of 20-30%. The first sign is microalbuminuria within a range of 30-300 mg/24h, frequently evolving towards frank proteinuria and renal failure. Tight glucose control, control of arterial hypertension with the use of ACEi or ARB can retard progression. Once renal failure is established, kidney transplantation can be considered for type 1 and type 2 diabetic patients. Quality of life and survival are improved with this procedure. In type 1 diabetes, simultaneous grafting of a kidney and pancreas considerably improves quality of life and diabetic complications. Surgical and infectious complications are sporadic drawbacks of this procedure. Pancreas transplantation alone (PTA) remains controversial, since a retrospective study in 2003 by Venstrom concluded that survival for PTA patients is worse than for comparable patients remaining on the waiting list. PTA can be considered for type 1 diabetic patients without advanced renal failure with severe and frequent metabolic instability (hypoglycaemia, ketoacidosis). Islet transplantation is still an experimental but promising procedure in highly selected patients, avoiding major abdominal surgery.

Diabetes Mellitus, Type 1↗

Urea kinetic modelling: comparison of three methods.

It has been claimed that computed urea kinetic (UK) modelling in haemodialysed patients for the estimation of protein intake and of the relation between total dialyser urea clearance and distribution volume (Kt/V) leads to an overestimation of protein catabolic rate (PCR). In the present study three different methods of kinetic modelling for the determination of PCR and Kt/V are compared in 15 patients. The first method (MI) is the direct quantification method based on the collection of all urea eliminated from the body. The two other methods are based on an iterative computed calculation. The second method (MII) is the urea kinetic modelling method as described by Sargent. Dialyser clearances were measured directly and not estimated by theoretical extrapolation. The third method described here (MIII), is based on the indirect calculation of urea distribution volume (Vw) according to Watson and of dialyser clearances from this Vw and from pre- and post-dialysis urea concentrations. All three methods result in PCRs that are not significantly different (MI: 1.04 +/- 0.29; MII: 1.07 +/- 0.28; MIII: 1.05 +/- 0.24 mg/kg BW per 24 h; p greater than 0.05). When the results are correlated, the following results are obtained: MI vs MII: r = 0.76, p less than 0.001; MI vs MIII: r = 0.78, p less than 0.001; MII vs MIII: r = 0.90, p less than 0.001. For Kt/V virtually identical results were obtained for each of the methods under study. In conclusion, all methods under study seem equally reliable in determining mean PCR.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

The effect of membrane permeability on ESRD: design of a prospective randomised multicentre trial.

The different permeability of high-flux and low-flux dialysis membranes results in different removal capacity, particularly for uremic toxins of middle and large molecular weight. High-flux dialysers have been evaluated in clinical and epidemiological studies for their effect on mortality, morbidity, dialysis-related amyloidosis, nutritional status, response to erythropoietin treatment, dialysis tolerance and the preservation of residual renal function. Many of these studies, however, lack a prospective design and randomised treatment allocation, or have too few patients and too short a follow-up. Therefore, this clinical trial was designed to prospectively investigate the long-term effect of membrane permeability on clinical outcome in a larger number of patients. The primary objective is to compare the effect of membrane permeability on mortality of patients on bicarbonate hemodialysis and treated with a minimum dialysis dose. Patients included in the study should have been on hemodialysis for no longer than one month and have serum albumin 4 g/dl or lower. Patients will be randomised to either the experimental or the control group. During the four-week run-in period the treatment parameters will be established in order to achieve the required dialysis dose. During the maintenance period of three to five years regular visits are scheduled to record clinical and laboratory parameters, to measure Kt/V and to adapt the treatment parameters. Altogether a minimum of 660 patients should be enrolled within a two-year recruitment period.

Humans↗

The role of peritoneal dialysis as the first-line renal replacement modality.

Twenty years after its introduction, peritoneal dialysis (PD) is a well-established alternative to hemodialysis (HD) as a modality of renal replacement therapy. Much debate and research is apparent in the literature, comparing hemodialysis and PD as "opposite" modalities and trying to ascertain which modality should be more optimal. In our opinion, HD and PD are two distinct modalities, each with its own advantages and disadvantages. In addition, it is clear that for both HD and PD, rates of technique failure are high, causing patients to transfer between modalities. The question is thus not which modality is best, but rather, which flow-chart of modalities makes best use of the advantages of each modality, while avoiding its disadvantages. In this respect, HD and PD appear to be complementary modalities. The better preservation of residual renal function, lower risk of infection with hepatitis B and C, better outcome after transplantation, preservation of vascular access, and lower costs are arguments to promote PD as a good initial treatment. When PD-related problems arise (adequacy, ultrafiltration, peritonitis, patient burnout), a timely transfer to HD has to be planned. This editorial tries to review arguments supporting the complementary nature of both modalities, and especially the role of PD as the first-line renal replacement therapy.

Costs and Cost Analysis↗

Waterborne Pseudomonas septicemia.

A small cluster of waterborne septicemias with Pseudomonas species occurred in a dialysis unit despite regular control of bacterial contents of tap water and dialysate conforming to preset standards. Pseudomonas aeruginosa, P. maltophilia, and/or P. vesicularis were found in the blood cultures of three patients in whom four pyrogenic reactions developed. The cluster occurred only in patients treated with formaldehyde-reused dialyzers. Pseudomonads were also cultured from the effluent of two dialyzers reprocessed with formaldehyde and not yet used; these two dialyzers had extremely low formaldehyde concentrations. The tap water used for dialyzer rinsing in the reuse procedure contained only 220 colony forming units/ml pseudomonads. The problem appeared to be related to the inadequate mixing of the sterilant with the tap water used in the automated reprocessing device--in the absence of an alarm for this failure. After immediate discontinuation of the reuse procedure with this device (that had been in use for 6 years) no further septicemic episodes were registered. It is concluded that septicemias may occur despite a bacteriologic contamination level of water conforming to preset standards. Such episodes can be avoided only by total water decontamination.

Aged↗