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Biomedical subjects

L A Monnens

Publications and source records attributed to L A Monnens.

At least 19 recordsLinked to original sources
PubMed2001

[Kidney insufficiency and persistent hypotension following compromise of the renin-angiotensin system in a fetus and a young infant].

A newborn girl had chronic renal failure following prenatal exposure to an angiotensin-converting enzyme (ACE) inhibitor, and a young infant with congenital nephrotic syndrome, showed persistent hypotension with neurological complications following bilateral nephrectomy at the age of 4 months. Both died. The renin-angiotensin system (RAS) is well-known for its regulatory function with respect to blood pressure, renal haemodynamics, fluid balance and electrolyte balance. Furthermore, its role in growth and differentiation of the kidneys and urinary tracts is becoming clearer. The RAS is highly important for the foetus and young infant. Extreme caution should be exercised with prenatal exposure to ACE inhibitors or angiotensin receptor blockers and bilateral nephrectomy in young infants.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

[Hemolytic uremic syndrome in children].

In Europe, haemolytic uraemic syndrome (HUS) is the most frequent cause of acute renal insufficiency during childhood. In the Netherlands about 20 children per year are seriously affected. Following a prodromal phase of mostly bloody diarrhoea, the main symptoms become evident, namely, haemolytic anaemia, thrombocytopenia and renal failure. The syndrome is caused by a verocytotoxin producing Escherichia coli, which damages the endothelium of the arterioles and glomeruli in the kidney. In humans, the most important cause of infection is the consumption of infected food-stuffs. After transport through the intestinal epithelium, the toxin becomes attached to the neutrophils, which transport it through the circulatory system, mainly to the kidneys where it has a toxic effect. Why the endothelial cells in these organs are the main targets for this toxin is as yet unknown. A symptomatic treatment is given to the 10% of infected patients who develop HUS. Increasing knowledge about the pathogenesis has resulted in new forms of treatment that will be studied during the next few years.

Acute Kidney Injury↗
PubMed2001

Persistent arterial hypotension after bilateral nephrectomy in a 4-month-old infant.

A patient with congenital nephrotic syndrome underwent bilateral nephrectomy at the age of 4 months. She showed persistent hypotension from the fourth postoperative day until death at the age of nearly 5 months. No cause for the hypotension could be found. It is postulated that, especially in young infants, a deficiency of renin after bilateral nephrectomy may cause persistent hypotension. An explanation for the putative increased risk of this complication in young infants may be their need for a highly active renin-angiotensin system. Until more is known about the incidence of this complication and its predisposing factors, reluctancy towards the performance of bilateral nephrectomy in children under the age of 6 months is warranted.

Blood Pressure↗
PubMed2001

The molecular basis of Dutch infantile nephropathic cystinosis.

Infantile nephropathic cystinosis, an inborn error of metabolism with an autosomal recessive inheritance pattern, is characterized by lysosomal storage of the amino acid cystine due to an impaired transport of cystine out of the lysosomes. Initial clinical features consist of the renal Fanconi syndrome and crystals in the cornea. Oral therapy with cysteamine lowers the intracellular cystine content. Recently, the gene coding for the integral membrane protein cystinosin, which is responsible for membrane transport of cystine (CTNS), was cloned. Mutation analysis of the CTNS gene of Caucasian patients revealed a common 57-kb deletion, and several other mutations spread throughout the entire gene. In the present study, we developed an improved screening method for the detection of the common 57-kb deletion. By use of this method we detected the 57-kb deletion in 59% of the examined Dutch alleles. The remaining alleles were screened for other mutations by genomic sequencing of the different exons, revealing three previously described mutations. Furthermore, we studied a possible genotype-phenotype relation of the homozygous deleted patients, which could not be demonstrated in our study population. Next to biochemical determination of cystine in leukocytes or fibroblasts, molecular genetic analysis enables prenatal diagnosis and facilitates identification of carriers.

Amino Acid Transport Systems, Neutral↗
PubMed2001

Detection of apoptosis in kidney biopsies of patients with D+ hemolytic uremic syndrome.

In this study we have investigated the presence of apoptotic cells in renal biopsy material of seven patients with hemolytic uremic syndrome (HUS) by using an improved and stringent terminal deoxynucleotidyl nick-end labeling (TUNEL) technique. Renal biopsy material was taken in the second or third week after onset of the disease. Renal biopsy material of patients with minimal lesions nephrotic syndrome or thin basement syndrome were used as control. It has been reported that nonapoptotic cells can be labeled nonspecifically due to proteinase K pretreatment or a delay in fixation when only TUNEL technique is used. In post mortem material this delay in fixation is seen. Moreover, it has been described that mainly nonapoptotic cells that shows signs of active gene transcription can be labeled in this nonspecific way. For this reason we used the TUNEL technique in combination with a label for RNA synthesis and splicing factor (SC-35). Indeed, we found nonspecific labeling of nonapoptotic nuclei in biopsy material of HUS patients, but not in control biopsy material. By using co-labeling with RNA synthesis factor SC-35, we were able to identify true apoptotic cells. There was a significant increase (p < 0.05) in the presence of apoptotic cells in biopsy material of HUS patients compared with material of controls. About 80 % of apoptotic cells were detected in tubuli and only 20 % in glomeruli of the renal biopsies of HUS patients. Furthermore, most apoptotic cells were detected in those patients that had received peritoneal dialysis suggesting that there is a relationship between severity of the disease and amount of apoptotic cells. The finding of apoptotic cells suggest that apoptosis plays a role in HUS.

Apoptosis↗
PubMed2000

[A child without edema in spite of albumin deficiency].

During extended investigation of a newborn girl with recurrent respiratory tract infection a continuous elevated blood sedimentation rate was noted together with a normal level of C reactive protein. This abnormality could be explained by analbuminaemia, causing a change in concentration of several other proteins such as transferrin. It was striking that this girl without albumin showed no signs of oedema. This lack of oedema could be explained by a decrease of oncotic pressure in the interstitium. Analbuminaemia is an autosomal recessive disorder. At follow-up the girl was still without complaints after 6 years.

Blood Sedimentation↗
PubMed2000

Binding and transfer of verocytotoxin by polymorphonuclear leukocytes in hemolytic uremic syndrome.

The hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in children. The role of a verocytotoxin (VT)-producing Escherichia coli has been strongly implicated in the epidemic form of HUS. Although direct toxicity of VT on glomerular endothelial cells has been demonstrated, it remained still unclear how the VT is transported from the intestine to the target organs. In this study we demonstrate that VT, when incubated in whole blood, binds rapidly and completely to human polymorphonuclear leukocytes (PMNs) and not to other components of blood. Binding studies with (125)I-VT-1 showed a single class of binding sites on freshly isolated, nonstimulated human PMNs. The K(d) of VT-binding to PMNs was 10(-8) mol/L, 100-fold less than that of the VT-receptor globotriaosylceramide. On incubation of VT-preloaded PMNs with human glomerular microvascular endothelial cells (GMVECs), transfer of VT-1 to the endothelial cells occurred. Incubation of nonstimulated GMVECs with VT-preloaded PMNs, but not with PMNs or VT-1 alone, caused inhibition of protein synthesis and cell death. Our data are in concert with a role of PMNs in the transfer of VT from the intestine to the kidney endothelium. This transfer occurs by selective binding to a specific receptor on PMNs and subsequent passing of the ligand VT to the VT-receptor on GMVECs, which causes cell damage. This new mechanism further underpins the important role of PMNs in HUS.

Adult↗
PubMed2000

Clinical experience with icodextrin in children: ultrafiltration profiles and metabolism.

Icodextrin use in adults provides sustained ultrafiltration (UF) in long-term dwells. No information is available on UF and metabolism in children. In 11 children, a volume of 1,049+/-138 ml/m2 of the study fluid (1.36% glucose, 7.5% icodextrin, 3.86% glucose) was administered for 12 h. Net UF with icodextrin (339+/-147 ml/1.73 m2) did not differ from UF with 3.86% glucose (450+/-306 ml/1.73 m2, P=0.53) and was higher than UF with 1.36% glucose (-87+/-239 ml/1.73 m2, P=0.003). Icodextrin added 0.52+/-0.07 to the weekly Kt/V. Over 6 weeks, icodextrin was used for 12-h daytime dwell. Total icodextrin reached a steady-state level of 2.91+/-1.22 g/l at 2 weeks. The main icodextrin metabolites were maltose, maltotriose, and maltotetraose. After 2 weeks, steady state levels were 2.02+/-0.66 mmol/l, 1.46+/-0.35 mmol/l, and 0.45+/-0.12 mmol/l. No icodextrin or metabolites were detectable 4 weeks after the study. We conclude that 7.5% icodextrin is capable of maintaining UF during 12-h dwell in children and is comparable to UF obtained with 3.86% glucose. Steady-state levels of icodextrin and metabolites were reached at 2 weeks and disappeared after the study.

Adolescent↗
PubMed2000

Dominant isolated renal magnesium loss is caused by misrouting of the Na(+),K(+)-ATPase gamma-subunit.

Primary hypomagnesaemia is composed of a heterogeneous group of disorders characterized by renal or intestinal Mg(2+) wasting, often associated with disturbances in Ca(2+) excretion. We identified a putative dominant-negative mutation in the gene encoding the Na(+), K(+)-ATPase gamma-subunit (FXYD2), leading to defective routing of the protein in a family with dominant renal hypomagnesaemia.

Alternative Splicing↗
PubMed2000

Severe linear growth retardation in rural Zambian children: the influence of biological variables.

BACKGROUND: The prevalence of stunting in preschool children in Zambia is high; stunting has detrimental effects on concurrent psychomotor development and later working capacity. OBJECTIVE: Our objective was to investigate biological variables that may contribute to linear growth retardation in preschool children in Samfya District, Zambia. DESIGN: Children aged 6-9 mo (n = 108) and 14-20 mo (n = 102) attending mother-and-child health clinics were included. With a mixed-longitudinal design, they were followed up 9 and 21 mo later. Height and weight of children and their mothers were measured. Biochemical measures (eg, serum zinc, retinol, thyrotropin, iron, and acute phase protein concentrations), malaria parasitemia, and intestinal parasitosis were assessed. RESULTS: Height-for-age z scores (HAZ) were low, indicating a high prevalence of stunting (36-79%). Ninety percent of the children were anemic, 53-71% had elevated acute phase proteins, and 80% had malaria parasitemia. Regression analyses showed that maternal height predicted the children's height at 6-9 mo (regression coefficient = 0.05; 95% CI: 0.02, 0.08). The children's height at an early age (6-9 and 14-20 mo) showed a strong relation with their height at later ages (22-30 and 34-41 mo). Serum micronutrient status did not show a significant relation with later HAZ. CONCLUSION: Unlike other studies, we did not identify specific biological factors, such as health and micronutrient status, which contribute to the retardation of linear growth. The normal zinc and iodine statuses of the children suggest that at least these factors are not causal.

Acute-Phase Proteins↗
PubMed2000

Hyperhomocysteinemia and other thrombotic risk factors in women with placental vasculopathy.

OBJECTIVE: To investigate coagulation inhibitors and abnormalities of the homocysteine metabolism, which are related to an increased thrombotic risk, as risk factors for placental vasculopathy. DESIGN: A case-control study comparing nonpregnant women with an obstetric history of placental vasculopathy (study group) with nonpregnant women (control group) matched for age and occupation. SETTING: Obstetric outpatient clinic in the University Hospital Nijmegen. SAMPLE: One hundred and one women in the study group and 92 women in a control group. METHODS: Determinations in blood samples of homocysteine concentrations; the occurrence of 677 C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene; protein C activities; activated protein C resistance ratios; concentrations of free protein S antigen; antithrombin III activities; and the occurrence of factor V Leiden mutation. RESULTS: Increased risk for placental vasculopathy was found in the study group with elevated homocysteine (odds ratio 2.28, 95% CI 1.18-4.39), MTHFR mutation (odds ratio 3.29, 95% CI 1.03-10.5), decreased activated protein C resistance ratio (odds ratio 2.46, 95% CI 1.06-5.72) and protein C (odds ratio 2.01, 95% CI 1.11-3.65). Any combination of two risk factors in the same individual resulted in a 3.40 (95% CI 1.80-6.42) higher relative risk for placental vasculopathy; combinations of three risk factors in a 6.83 (95% CI 1.52-30.7) higher risk. CONCLUSIONS: The thrombotic risk factors decreased levels of activated protein C resistance ratios and protein C, elevated homocysteine and the MTHFR 677 C-->T mutation are likely risk factors for placental vasculopathy. Combinations of these risk factors in one individual resulted in synergistic increase of risk.

Activated Protein C Resistance↗
PubMed2000

Autosomal dominant Alport syndrome caused by a COL4A3 splice site mutation.

BACKGROUND: Alport syndrome (AS) is a clinically and genetically heterogeneous renal disorder, predominantly affecting the type IV collagen alpha 3/alpha 4/alpha 5 network of the glomerular basement membrane (GBM). AS can be caused by mutations in any of the three genes encoding these type IV collagen chains. The majority of AS families (85%) are X-linked (XL-AS) involving mutations in the COL4A5 gene. Mutations in the COL4A3 and COL4A4 genes cause autosomal recessive AS (AR-AS), accounting for approximately 14% of the cases. Recently, autosomal dominant AS (AD-AS) was linked to the COL4A3/COL4A4 locus in a large family. METHODS: COL4A3 and COL4A4 cDNAs were generated by nested reverse transcription-polymerase chain reaction and were analyzed by DNA sequence analysis. Denaturating high-performance liquid chromatography (DHPLC) was used for mutation and segregation analysis at the genomic DNA level. RESULTS: In the AD-AS family, a splice site mutation resulting in skipping of exon 21 of the COL4A3 gene was detected. The mutation does not alter the reading frame and is predicted to result in a COL4A3 chain with an internal deletion. CONCLUSION: As the NC domain is intact, this chain may be incorporated and distort the collagen triple helix, thereby causing the dominant effect of the mutation. The finding of a specific COL4A3 mutation in AD-AS completes the spectrum of type IV collagen mutations in all genetic forms of AS.

Adult↗
PubMed2000

Consequences of infections for three-month length increment in young children in rural Zambia.

It was the aim of this study to describe the relationship of infections with subsequent 3-mo length increment in children below 2 y of age in rural Zambia. Children aged 6-9 mo ('infants'; n = 84) and 14-20 mo ('toddlers'; n = 81) attending Mother-and-Child Health clinics, were included and followed up after 3.0 mo (min-max; 2.1-3.7 mo). Anthropometric measurements were taken at each visit. At baseline, C-reactive protein (CRP), alpha1-acid glycoprotein (AGP), retinol and malaria parasitaemia were assessed. Length increment during the 3.0+/-0.5 mo was 1.0+/-0.5 cm/mo for infants and 0.6+/-0.4 cm/mo for toddlers; 50-71% of the children showed increased acute phase proteins, 79-83% had malaria parasitaemia and 55-64% had low serum retinol concentrations. In the total group of children, serum AGP concentrations (r = -0.18; p = 0.03) and serum CRP concentrations (r = -0.15; p = 0.05) showed a negative relation with length increment. After correcting for micronutrient status, dietary intake and maternal height, results of multiple regression analyses showed that the relation between serum AGP concentration and subsequent length increment remained significant. We conclude that, within the multifactorial model, presence of infections in these Zambian children contributes to the short-term retardation of linear growth.

Acute Disease↗
PubMed2000

Nutritional status of breastfed infants in rural Zambia: comparison of the National Center for Health Statistics growth reference versus the WHO 12-month breastfed pooled data set.

Cross-sectional data for breastfed infants in rural Zambia were used to evaluate the effect of applying two different data sets as a reference, i.e. the WHO 12-month breastfed pooled data set and the National Center for Health Statistics (NCHS) growth reference in terms of prevalence of malnutrition (stunting, underweight, and wasting). A total of 518 infants who were attending mother-and-child health clinics were included. Age, weight and length were recorded. Anthropometric Z-scores were calculated in two ways: by applying the NCHS growth reference and by using the WHO breastfed data set. Anthropometric Z-scores calculated using the breastfed data set were lower during the first 6-7 months of life compared with those calculated by applying the NCHS growth reference. This resulted in a higher proportion of children aged 0-6 months being classified as stunted and underweight using the breastfed data set versus the NCHS growth reference. After the age of 7 months, similar prevalences of stunting or underweight were observed. Relatively few infants were classified as wasted. In order to adequately assess the prevalence of stunting and underweight in breastfed infants, it is recommended that a new growth reference be developed, as has been initiated by WHO.

Breast Feeding↗