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Biomedical subjects

W Smit

Publications and source records attributed to W Smit.

At least 19 recordsLinked to original sources

Analysis of fluid transport pathways and their determinants in peritoneal dialysis patients with ultrafiltration failure.

Ultrafiltration failure (UFF) is a serious complication of peritoneal dialysis (PD). The aim of the study was to analyze changes in water transport and their determinants in UFF patients over the time on PD. Standard peritoneal permeability analyses of 50 stable PD patients with UFF were analyzed. Fluid transport through small pores (SPT), free water transport (FWT) at 60 min, their contributions on total ultrafiltration (SPTC and FWTC), and their determinants were assessed. Patients were divided in Group I (UFF) treated for less than 24 months, Group II treated 24-60 months, and Group III treated for more than 60 months. Group I (UFF) was compared with Group I (non-UFF) matched for the duration of PD treatment and age. Transcapillary ultrafiltration (TCUF), SPT, FWT, and FWTC were significantly lower in Group III when compared to the other UFF groups. In this group also, negative relationship was present between FWT, the ultrafiltration coefficient LpA, and osmotic conductance to glucose on one hand and PD duration on the other. FWT was positively related to osmotic conductance to glucose in all groups. Group I (UFF) showed significantly higher solute transport, effective lymphatic absorption rate, lower TCUF, and lower FWT than Group I (non-UFF). The patterns of UFF in PD patients are dependent on the duration of treatment.

Adult↗

When to start dialysis?

In an attempt to decrease mortality in dialysis patients, the care for end-stage renal disease patients has been a focus of nephrologists for many years. Good pre-dialysis care has been found to improve mortality numbers in several studies. However, it is still not exactly clear, when the best moment has arrived to start renal replacement therapy. By illustrating two totally different patient cases the effect of outcome and quality of life are discussed-demonstrating on the one hand the role of clinical parameters, and on the other hand the influence of biochemical parameters.

Aged↗

Adequacy of peritoneal dialysis and the importance of preserving residual renal function.

The well-being and survival of dialysis patients not only depend on the removal of waste products and excess fluid, but also on the prevention of cardiovascular complications by maintaining normovolaemia and adequate blood pressure and avoidance of ectopic calcification. Also, the maintenance of nutritional status and adequate removal of middle molecules are amongst the most important issues in long-term renal replacement therapy. In this review, attention is given to optimal peritoneal small solute clearance and Kt/V and to the evidence concerning the role of residual renal function. In addition, factors that can influence this residual function are also discussed.

Creatinine↗

Histological changes over time around the site of sustained release naltrexone-poly(DL-lactide) implants in humans.

In order to assess the histological tissue changes over time around the site of implant, tissue biopsies were taken at 1 to 38 months post-implant from 54 (34 male) consenting human subjects who had received the Australian subcutaneous naltrexone-poly(DL-lactide) implant for heroin dependence. The implant consists of multiple tablets containing compressed naltrexone-poly[trans-3,6-dimethyl-1,4-dioxane-2,5-dione] (DL-lactide) loaded microspheres. Assessment of tissue samples by pathologists showed an early phase (up to 12 months post-implant) of inflammation, foreign body reaction, and fibrosis. This subsided gradually over the next 12 months until tissue returned to normal by 25+ months. Sufficient evidence was not available to conclude that the poly(DL-lactide) implant matrix was totally biodegradable within the study period. While implant material was not identified in most of the latter biopsies, its presence was noted in one biopsy at 26 months post-implant. Nevertheless the study results did demonstrate the implant's biocompatibility by the lack of inflammation, foreign body reaction, and fibrosis detected by 25+ months. It seems highly probable that surgical technique rather than the implant itself was associated with the additional finding of fat necrosis. Moderate fat necrosis was observed as a common feature of biopsies carried out during the first 6 months following implant. It subsided to mild levels over the next 18 months, and was notably absent by 25+ months. The results of the study indicated that the Australian naltrexone-poly(DL-lactide) implant is well tolerated and may have a role for use in the management of medical conditions such as heroin dependence.

Biocompatible Materials↗

Guanidinoacetate methyltransferase deficiency identified in adults and a child with mental retardation.

Our study describes the adult clinical and biochemical spectrum of guanidinoacetate methyltransferase (GAMT) deficiency, a recently discovered inborn error of metabolism. The majority of the previous reports dealt with pediatric patients, in contrast to the present study. A total of 180 institutionalized patients with a severe mental handicap were investigated for urine and plasma uric acid and creatinine. Patients with an increased urinary uric acid/creatinine ratio and/or decreased creatinine were subjected to the analysis of guanidinoacetate (GAA). Four patients (three related and one from an unrelated family) were identified with GAMT-deficiency. A fifth patient had died before a biochemical diagnosis could be made. They all had shown a normal psychomotor development for the first year of life, after which they developed a profound mental retardation. Three out of four had convulsions and all four totally lacked the development of speech. Their GAMT activity in lymphoblasts was impaired and two novel mutations were identified: the 59 G > C and 506 G > A missense mutations. Urinary GAA was increased, but highly variable 347-1,624 mmol/mol creat (Controls <150 mmol/mol creat). In plasma and CSF the GAA levels were fairly constant at 17.3-27.0 mumol/L (Controls 1.33-3.33) and 11.0-12.4 mumol/L, respectively (Controls 0.068-0.114). GAMT deficiency in adults is associated with severe mental retardation and absence or limited speech development. Convulsions may be prominent. The nonspecific nature of the clinical findings as well as the limited availability of GAA assays and/or in vivo magnetic resonance spectroscopy of the brain may mean that many more patients remain undiagnosed in institutions for persons with mental handicaps.

Abnormalities, Multiple↗

Ultrafiltration failure in peritoneal dialysis. Causes and clinical consequences.

Ultrafiltration failure (UFF) is the insufficient ability to remove excess fluid from the body by dialysis. In peritoneal dialysis (PD) this is a common complication, the frequency increases with duration of treatment. In this review a summary of peritoneal transport mechanisms and the conditions associated with UFF are discussed. The 2 most common circumstances in which ultrafiltration failure occurs, peritonitis and long-term PD treatment, are outlined more extensively. In addition a diagnostic approach and therapeutic options for the different causes of UFF are given.

Humans↗

Vascular endothelial growth factor in peritoneal dialysis: a longitudinal follow-up.

In a previous study, vascular endothelial growth factor (VEGF) was found to be locally produced in the peritoneal tissue of patients undergoing peritoneal dialysis (PD) who were being treated with glucose-containing PD solutions. Locally produced VEGF (LVEGF) was positively related to the mass transfer area coefficient (MTAC) of creatinine and to glucose absorption, both of which are representative of the peritoneal vascular surface area. It was therefore hypothesized that VEGF is involved in the peritoneal neoangiogenesis found in long-term PD. The aim of the present study was to investigate the time course of peritoneal VEGF levels in PD patients treated with glucose-based PD solutions during longitudinal follow-up. We also studied the effect of the switch to glucose-free PD treatment on VEGF production. Forty standard peritoneal permeability analyses (SPAs) with 3.86% glucose-containing dialysis solution were investigated. The SPAs were performed in 10 PD patients with a median number of three SPAs per patient during a follow-up of 23 months. Duration of PD treatment at the last SPA was 74 months. All patients were initially treated with glucose-containing dialysis solutions. Four patients switched after 114 months of glucose-based PD to glucose-free PD and were followed for 7 months. A PD regimen of icodextrin, glycerol, and amino acid-based dialysis solutions was applied in these patients. Four SPAs were performed per patient in this period. To predict the VEGF dialysate-to-serum ratio (D/S), when diffusion would be the only explanation for the VEGF dialysate concentration, we calculated the power relationship between D/S ratios of serum proteins that are only transported across the peritoneum and the molecular weights of those proteins. The measured VEGF D/S ratio was higher than expected (P <.001) in each observation, pointing to local production of VEGF. LVEGF increased with duration of glucose PD, 11.7 ng/L to 23.45 ng/L (P <.03). LVEGF decreased in all 4 patients undergoing glucose-free PD, from 57.35 ng/L to 23.10 ng/L. A correlation (r = 0.83, P <.001) was found be-tween the differences in MTAC creatinine between the first and last SPA during glucose-based PD and the difference in LVEGF between these observations. A similar correlation was present between the difference in glucose absorption and the difference in LVEGF (r = 0.85, P <.001). This supports a pathogenetic role of high glucose dialysate concentrations in the development of changes in the peritoneum that are found in long-term PD. Treatment with non-glucose-based PD solutions may inhibit further development of these alterations.

Amino Acids↗

Growth factors VEGF and TGF-beta1 in peritoneal dialysis.

The morphologic alterations in the kidney and the retina that can be present in patients with diabetic microangiopathy are mediated by growth factors. Vascular endothelial growth factor (VEGF) is a mediator of neoangiogenesis in diabetic retinopathy. Transforming growth factor-beta (TGF-beta) is involved in the extracellular matrix proliferation in diabetic nephropathy. The aim of the present study was to investigate the presence of VEGF and TGF-beta1 in peritoneal effluents of patients undergoing continuous ambulatory peritoneal dialysis who are being treated with glucose-containing dialysis solutions in relation to parameters of peritoneal transport. Standard peritoneal permeability analyses with 3.86% glucose dialysate were performed in 16 stable patients undergoing peritoneal dialysis (PD) (median duration of PD 39 months, range 1 to 104 months). The power relationship that is present between dialysate/serum (D/S) ratios of serum proteins that are transported only across the peritoneal membrane and their molecular weights was used to predict the D/S ratios when diffusion would be the only explanation for the measured dialysate concentration. It was assumed that all TGF-beta1 in the circulation was bound to alpha2-macroglobulin. The D/S ratios of VEGF (P < .0005) and TGF-beta1 (P < .015) were significantly higher than expected when VEGF and TGF-beta1 would have been transported from the circulation only by diffusion. No relationship was present between the effluent concentration attributed to the local production of VEGF (LVEGF) and that of TGF-beta1 (LTGF-beta1). LVEGF correlated with the mass transfer area coefficient (MTAC) creatinine value (r = 0.69, P < .007), MTAC urate value (r = 0.60, P < .02), and glucose absorption value (r = 0.75, P < .004), all reflections of the peritoneal vascular surface area. A negative correlation was observed between the transcapillary ultrafiltration (926 mL/4 h, 394 to 1262 mL/4 h) and LVEGF (r = -0.52, P < .045). This negative tendency was also observed between the net ultrafiltration (622 mL/4 h, -43 to 938 mL/4 h) and LVEGF (r = -0.48) but did not reach significance. LVEGF and the duration of treatment did not correlate, possibly because of the relatively small number of patients. LTGF-beta1 showed no relationship with transport parameters or duration of treatment. In conclusion, we found evidence for the local production of both VEGF and TGF-beta1 in the peritoneal membrane of patients undergoing long-term peritoneal dialysis with glucose-based dialysate solutions. The analogy with VEGF in diabetic retinopathy suggests a pathogenetic role of high dialysate glucose concentrations in the development of these alterations in the peritoneal membrane.

Biological Transport↗

Controlled comparison of induction versus expectant care for prelabor rupture of the membranes at term.

This randomized clinical trial compared oxytocin induction of labor with expectant care for 48 hours after prelabor rupture of the membranes at term. Women at term with prelabor rupture of the membranes for at least 8 hours were assigned at random to induction with oxytocin or to expectant management for 48 hours followed by induction if necessary. Of 168 eligible women, 123 (73%) agreed to participate. More women in the induction group (23%) than in the expectant group (10%) had operative delivery, either cesarean section or instrumental vaginal delivery. In the induction group 41% received analgesia versus 24% in the expectant group (p < 0.005). There was no difference in the rate of maternal and neonatal infection between groups and sepsis was not observed. The active policy of oxytocin induction exposed the mother to a higher risk of operative delivery and a less comfortable labor than the 48 hours expectant care option.

Analgesia, Obstetrical↗

Controversies: prelabor rupture of the membranes at term: the case for expectant management.

Review of the controlled comparisons between induction of labor and expectant care after prelabor rupture of the membranes (PROM) at term indicates that they are not unhelpful for deciding which of the two options is best. This is, first, because there is a large potential for bias in the studies reported thus far. Second, the trials are rather heterogeneous and they are comparisons more between early and late induction than between induction and expectant care. Third, it is difficult to weigh an increased risk of operative delivery with the induction policy against an apparently clear, but almost certainly biased, reduction of neonatal infection. With expectant care about 70% of women will give birth within 24 hours and 85% within 48 hours. The majority of these women will derive little, if any, benefit from induction and a routine policy of induction of labor after PROM cannot be justified on the basis of the data that are available.

Cesarean Section↗

Dopaminergic and GABAergic cerebrospinal fluid-contacting neurons along the central canal of the spinal cord of the eel and trout.

In anamniote vertebrates the central region of the spinal cord has been implicated in its regeneration. This is a complex region and so as a first step in understanding its possible regenerative role we have examined the organization of the cells that contact the lumen of the spinal cord in two teleost fishes, eel and trout, using immunohistochemical procedures and light and electron microscopy. Cell bodies immunoreacting positively with antibodies for tyrosine hydroxylase and for dopamine were located at the ventral rim of the central canal, whereas cell bodies reacting for an antibody for gamma-aminobutyric acid were more laterally located. None of the canal-contacting cells were positively immunoreactive for choline acetyltransferase. All immunopositive cells have a similar morphology: the amphora-shaped perikaryon is bipolar and has a single process that extends to the lumen of the canal, and another that branches and forms extensive lateral and ventral plexuses. Electron microscopic investigations of the ventral dopaminergic cells showed that the apical processes bear one or more cilia, which protrude into the canal lumen and which originate from within a superficial rosette of nonciliated processes. The ventral process was occasionally seen to form synapses; the cell body was also the target of synapses.

Animals↗

Some aspects of melanin formation of melanocytes cultured on collagen-coated microcarrier beads.

Melanocytes cultured on collagen-coated Cytodex 3 microcarrier Sephadex beads caused remarkable pigmentation of the beads during the period of culture when optimal density was reached. Electron microscopy of melanocytes on the microcarriers revealed that the cells and their dendrites invaginate into the microcarrier surface layer. Removal of the cells by trypsinization showed that some pigment granules were left on the carrier surface and within the cavities present on the microcarrier surface. In order to investigate whether the pigmentation of the microcarriers could be a result of indole intermediates of melanogenesis present in the culture medium, extracts were studied by gas chromatography/mass spectrometry for the presence of these compounds. Two compounds (5,6-dihydroxyindole-2-carboxylic acid and 6-hydroxy-5-methoxyindole-2-carboxylic acid) so far have been identified in the medium extracts. Results indicate that microcarrier culture of melanocytes can serve as an interesting model for electron microscopy studies of melanocytes with regard to pigmentation and cell attachment.

Cell Adhesion↗

Pancreatic cytology and adenosquamous carcinoma of the pancreas.

Primary carcinoma of the pancreas exhibiting squamous differentiation is unusual. We present such a case which was diagnosed by percutaneous fine needle aspiration biopsy. A cytological diagnosis of squamous cell carcinoma lead to the question: was the tumour primary or secondary? Subsequent post-mortem examination confirmed a primary carcinoma of the head of the pancreas with predominantly squamous differentiation and a small component of glandular differentiation. Cytologic diagnosis of squamous cell carcinoma should prompt a review of clinical and radiologic data. Evidence of a malignant glandular component should also be sought.

Aged↗