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2.
Eur J Intern Med ; 20(7): 682-5, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19818286

ABSTRACT

We present a patient with a rare cause of ectopic ACTH-dependent Cushing's syndrome, caused by a pheochromocytoma. The case provides clues for a detailed discussion on the pitfalls and diagnostic difficulties in establishing the correct underlying cause of ACTH-dependent Cushing's syndrome. It clearly demonstrates that the relative contributions of clinical, biochemical, and radiological clues in establishing the correct underlying cause of Cushing's syndrome may differ considerably between Cushing's disease and Cushing's syndrome due to ectopic overproduction of ACTH. In addition, the literature concerning ACTH-producing pheochromocytomas is reviewed.


Subject(s)
Adrenal Gland Neoplasms/metabolism , Adrenocorticotropic Hormone/metabolism , Hormones, Ectopic/metabolism , Pheochromocytoma/metabolism , Adrenal Gland Neoplasms/complications , Adrenal Gland Neoplasms/diagnosis , Aged , Cushing Syndrome/etiology , Humans , Male , Pheochromocytoma/complications , Pheochromocytoma/diagnosis
3.
Neth J Med ; 66(10): 438-41, 2008 Nov.
Article in English | MEDLINE | ID: mdl-19011271

ABSTRACT

Case report of a 62-year-old woman who developed acute renal failure due to nephrocalcinosis, also called acute phosphate nephropathy, after large bowel cleansing in preparation for colonoscopy using oral sodium phosphate solution (Phosphoral, de Witt, Cheshire, UK). Subsequently her renal insufficiency resolved only partially resulting in stage 4 chronic kidney disease. In retrospect multiple risk factors for this condition (hypertension, diuretics, AT-II receptor blocker, female gender, advanced age and volume depleting due to vomiting and nausea) were identified. If these factors had been taken into consideration prior to prescribing this drug, acute and chronic renal failure would have been prevented. Future investigation of potential risk factors and the exact mechanism of this complication is necessary to identify those patients prone to develop this complication. In the meantime prescribing physicians should be made aware of this complication. On the basis of the current state of knowledge the evidence seems to be quite compelling not to prescribe these drugs in patients with one or more associated risk factors. It could even be argued that these drugs should not be prescribed at all.


Subject(s)
Acute Kidney Injury/chemically induced , Cathartics/adverse effects , Nephrocalcinosis/chemically induced , Phosphates/adverse effects , Colonoscopy , Contraindications , Female , Humans , Middle Aged , Nephrocalcinosis/complications
4.
Kidney Int ; 73(12): 1426-33, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18354379

ABSTRACT

Treatment of patients with IgA nephropathy (IgAN) depends on a reliable assessment of disease progression based on measurements of glomerular filtration rate (GFR), proteinuria, hypertension, and tubulointerstitial changes. We sought to determine whether progression could be predicted from analysis of glomerular and tubulointerstitial inflammation in biopsies taken at an early stage of IgAN. We retrospectively analyzed biopsies from 50 patients, relating the subsequent clinical course to infiltration with B- and T-lymphocytes, granule membrane protein of 17 kDa (GMP-17) positive cytotoxic T cells, macrophages, fibroblasts, and tubulointerstitial expression of human leukocyte antigen-D related (HLA-DR). At biopsy, 19 patients had decreased GFR while 13 of 31 patients with normal GFR and progressive IgAN differed significantly from 18 non-progressors in the level of proteinuria and in the severity of scores for mesangial proliferation, tubular atrophy, interstitial fibrosis, and interstitial infiltrates. On multivariate regression analysis these differences disappeared; however, associations with GMP-17-positive cytotoxic T-lymphocytes in intact renal tubules and of B-lymphocytes in the interstitium remained significant. Our study may have identified a marker of disease progression in early stages of IgAN.


Subject(s)
Glomerulonephritis, IGA/pathology , Kidney Tubules/pathology , Membrane Proteins/analysis , T-Lymphocytes, Cytotoxic/immunology , Biomarkers/analysis , Disease Progression , Female , Glomerular Filtration Rate , Glomerulonephritis, IGA/immunology , Glomerulonephritis, IGA/physiopathology , HLA-DR Antigens/analysis , Humans , Kidney Tubules/immunology , Kidney Tubules/physiopathology , Male , Prognosis , Regression Analysis , Retrospective Studies
5.
Clin Toxicol (Phila) ; 46(1): 74-8, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18167039

ABSTRACT

The plastic hardener methyl ethyl ketone peroxide (MEKP) is an unstable peroxide that releases free oxygen radicals. Ingestion of this compound induces widespread liver necrosis that is often fatal, extensive ulceration with subsequent scarring, and stenosis of the proximal digestive tract in survivors. Severe metabolic acidosis occurs due to the accumulation of formic acid and other organic acids inducing neurologic damage, such as optic nerve lesions. A 53-year-old man unintentionally ingested approximately 120 ml of a 33% solution of this compound in dimethylphtalate. The patient was treated with the free radical scavenger N-acetylcysteine to counteract free radical-mediated damage and with hemodialysis to remove accumulated organic acids. Although our patient demonstrated considerable edema and ulceration of the distal esophagus, stomach and duodenum in the acute phase, there was never any sign of liver damage or neurological damage, nor were there any demonstrable lesions in the proximal digestive tract three weeks after the event. Treatment with a combination of N-acetylcysteine and haemodialysis may be a promising therapy for this severe and potentially life-threatening intoxication.


Subject(s)
Acetylcysteine/therapeutic use , Butanones/poisoning , Free Radical Scavengers/therapeutic use , Renal Dialysis , Acidosis/prevention & control , Edema/chemically induced , Free Radicals/metabolism , Free Radicals/toxicity , Gastrointestinal Diseases/chemically induced , Humans , Liver/drug effects , Liver/pathology , Male , Middle Aged , Phthalic Acids
6.
Ned Tijdschr Geneeskd ; 150(43): 2370-6, 2006 Oct 28.
Article in Dutch | MEDLINE | ID: mdl-17100128

ABSTRACT

The 'Stichting Werkgroep Antibioticabeleid' (SWAB; Dutch Working Party on Antibiotic Policy) has developed an evidence-based guideline for the empirical antimicrobial treatment of complicated urinary tract infections (UTIs) in hospitalised adult patients. The choice of treatment is based on recent Dutch data on the resistance ofuropathogens to the most frequently used antibiotics. The first choice for empirical antibiotic treatment in a patient with a complicated UTI is a 2nd or 3rd generation cephalosporin or the combination of amoxicillin and gentamicin. Amoxicillin-clavulanic-acid intravenously is the second empirical choice. The treatment duration must be at least 10 days. The treatment must be adjusted after the results of the urine culture become known and made more specific if possible. Oral treatment can be given if the patient's clinical situation allows it. There are separate recommendations for the treatment ofUTIs in the following patient categories: men, pregnant women, patients with a urinary catheter, patients with diabetes mellitus and patients with renal diseases, congenital polycystic kidney disease or pyocystis.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteriuria/drug therapy , Practice Guidelines as Topic , Pregnancy Complications, Infectious/drug therapy , Urinary Tract Infections/drug therapy , Bacteriuria/microbiology , Drug Resistance, Bacterial , Drug Therapy, Combination , Female , Health Policy , Health Status , Humans , Male , Netherlands , Pregnancy , Pregnancy Complications, Infectious/microbiology , Time Factors , Urinary Tract Infections/microbiology
7.
J Pathol ; 193(2): 256-62, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11180174

ABSTRACT

Fibronectin (FN) is an extracellular matrix component which appears in different isoforms, due to alternative mRNA splicing of the ED-A, ED-B, and IIICS regions, and subsequent post-translational modifications. The FN isoforms, some of which occur specifically during fetal development and in fibrogenic diseases, have been reported to play a role in various biological functions, such as regulation of the matrix assembly, adhesion, and proliferation. The contribution of these FN isoforms to the pathogenesis of chronic renal diseases, which are also fibrogenic disorders, is not well known. This study therefore examined the distribution of FN isoforms in renal diseases by immunohistochemistry, with a panel of isoform-specific monoclonal antibodies (MAbs), applied to 63 abnormal renal biopsies and ten normal controls. Normal kidneys contained total FN (MAb IST4) both in the mesangial and in the interstitial extracellular matrix (ECM), but only traces of ED-A-positive FN (MAb IST9), and no ED-B-positive FN (MAb BC1) or oncofetal FN (MAb FDC6) was found in normal renal tissue. All patients with renal disease demonstrated increased total FN staining of the interstitium and the mesangium. Periglomerular fibrotic lesions and fibrous crescents showed massive accumulation of total FN, whereas the amount of total FN in the ECM of obsolescent glomeruli was decreased, compared with that in normal mesangial ECM. Oncofetal (FDC6), EDB-negative (MAb IST6), ED-A-positive, and ED-B-positive FN isoforms were found in glomerular ECM accumulations and in fibrous crescents. Tubulointerstitial fibrotic lesions predominantly contained the ED-A-positive FN isoform, whereas in globally sclerotic glomeruli, predominantly ED-B-positive FN was observed. The expression of FN isoforms was similar in all renal diseases studied. These results show that in various renal diseases, oncofetal (FDC6) FN and ED-A- and ED-B-positive isoforms of FN accumulate at locations of chronic lesions, independently of the aetiology of the disease. The deposition of these isoforms in human renal tissue may play a role in the modulation of the immune response by attracting monocytes and lymphocytes to the injured kidney. Furthermore, because the ED-B-positive FN isoform is highly susceptible to proteolytic degradation, its accumulation may play a role in scar formation and tissue repair. ED-B-positive FN forms a temporary scaffold supporting the cells, which can easily be cleared by proteolytic degradation once new tissue has been produced at the site of injury.


Subject(s)
Fibronectins/metabolism , Kidney Diseases/metabolism , Adult , Aged , Alternative Splicing , Antibodies, Monoclonal , Case-Control Studies , Female , Fibrosis , Humans , Kidney Diseases/pathology , Male , Middle Aged , Protein Isoforms/metabolism
8.
Clin Nephrol ; 51(3): 133-40, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10099885

ABSTRACT

BACKGROUND: The insertion-deletion (I/D) polymorphism of the angiotensin converting enzyme gene is a diallelic polymorphism that constitutes a genetic influence on the progression of renal diseases such as IgA nephropathy. Patients with the DD genotype have an accelerated progression towards end stage renal failure in these diseases. The role of the I/D polymorphism in the pathogenesis of diabetic nephropathy in IDDM is unresolved. PATIENTS AND METHODS: We therefore set out to study the contribution of the I/D polymorphism in 79 patients (age 39.5 +/- 7.6 years (mean +/- SD) with end stage renal failure due to diabetic nephropathy, who were recipients of a combined kidney-pancreas transplantation (n = 60), or who were on the waiting list for such a procedure (n = 19). The control series consisted of 82 patients (age 39.5 +/- 9.6 years) without microalbuminuria after fifteen years of IDDM. RESULTS: The ACE genotype distribution in patients was not in accordance with the Hardy-Weinberg equilibrium due to a significant overrepresentation of the DD genotype (X2 = 8.9, p = 0.01). This resulted in a significant increase of the D-allele frequency in the cases compared to controls (X2 = 4.9, p = 0.03). The presence of one D-allele did not increase the risk of end stage renal failure (odds ratio ID/II = 1.0, 95% CI 0.4-2.2). The presence of the DD genotype increased the risk of end stage renal failure twofold compared to the other genotypes (odds ratio 2.1, 95% CI 1.1-4.0). The risk estimate seemed slightly higher in patients with good metabolic control (odds ratio 2.6, 95% CI 1.0-7.1), than in patients with poor control (odds ratio 1.6, 95% CI 0.59-4.3). CONCLUSION: It is concluded that the risk of end-stage renal failure in patients with IDDM is twofold increased in patients with the DD genotype as compared to patients with other genotypes.


Subject(s)
Diabetes Mellitus, Type 1/complications , Diabetic Nephropathies/genetics , Kidney Failure, Chronic/genetics , Peptidyl-Dipeptidase A/genetics , Adult , Case-Control Studies , Diabetes Mellitus, Type 1/genetics , Diabetic Nephropathies/etiology , Disease Progression , Female , Genotype , Humans , Kidney Failure, Chronic/etiology , Male , Polymorphism, Genetic , Risk Assessment
9.
Neth J Med ; 54(3): 114-28, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10189786

ABSTRACT

All glomerular kidney disorders with the exception of minimal change disease are characterized by a progressive decline of renal function in association with progressive glomerulosclerosis and tubulointerstitial fibrosis of the kidneys involved. This almost universal association seems to suggest that the progressive loss of kidney function results from a fibrogenic pathogenetic mechanism that serves as a final common pathway with the initial insult to the glomerulus initiating a cascade of events including an early inflammatory phase followed by a fibrogenic response in the glomerular and the tubulointerstitial compartments of the kidneys. The present review will address the pathogenesis of this fibrogenic process covering the interplay between glomerular and tubulointerstitial events, the roles of recruited and resistant cells, cytokines, growth factors and the extracellular matrix.


Subject(s)
Glomerulonephritis/physiopathology , Kidney Failure, Chronic/physiopathology , Cytokines/metabolism , Disease Progression , Extracellular Matrix , Fibrosis/physiopathology , Glomerulonephritis/immunology , Humans , Kidney Failure, Chronic/immunology
10.
Clin Nephrol ; 49(6): 337-44, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9696428

ABSTRACT

It is generally accepted that the severity of renal insufficiency in patients correlates with the severity of tubulointerstitial abnormalities, but not with the severity of glomerular abnormalities in kidney biopsies. We recently challenged this view by demonstrating significant correlations of glomerular structural abnormalities with renal function in a histomorphometric study of biopsies from patients with various kidney diseases. We set out to confirm these findings in biopsies from patients with a single disease entity. IgA nephropathy was selected. An additional objective of the study was to determine the prognostic value of our histological predictors of renal function. Histomorphometric measurements were done in silver- and PAS-stained paraffin sections of biopsies from 83 patients with primary IgA nephropathy. The results were correlated with creatinine clearance at the time of biopsy. The prognostic value of the histomorphometric parameters and of several clinical characteristics were determined in a Cox proportional hazard model. All glomerular histomorphometric indices correlated with the severity of renal insufficiency, but quantitative estimates of the glomerular deposition of periodic acid-Schiff positive extracellular matrix (PAS-index) seemed to be the most important glomerular structural-functional correlate (r = 0.53, p<0.001). However, the correlation of quantitative estimates of the severity of interstitial extracellular matrix accumulation with renal function (quantitative interstitial index) was superior (r = 0.76, p<0.001). Creatinine clearance at biopsy and initial proteinuria were the strongest clinical predictors of renal survival. The severity of tubulointerstitial extracellular matrix accumulation was the strongest histological predictor of an adverse outcome. In conclusion, quantitative estimates of the severity of glomerular and tubulointerstitial extracellular matrix accumulation both correlate well with the severity of renal failure in biopsies from patients with IgA nephropathy. Creatinine clearance at biopsy, initial proteinuria and the severity of tubulointerstitial extracellular matrix accumulation are the best predictors of renal survival. On a more general note, the paradigm of the absence of correlation of glomerular pathology with renal function should be abandoned.


Subject(s)
Glomerulonephritis, IGA/pathology , Adult , Biopsy , Extracellular Matrix/metabolism , Female , Glomerulonephritis, IGA/metabolism , Glomerulonephritis, IGA/physiopathology , Humans , Kidney/physiopathology , Kidney Glomerulus/metabolism , Kidney Glomerulus/pathology , Male , Periodic Acid-Schiff Reaction , Prognosis , Renal Insufficiency/pathology , Renal Insufficiency/physiopathology
11.
Clin Nephrol ; 47(3): 158-67, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9105762

ABSTRACT

General agreement exists on the correlation of renal insufficiency with the severity of tubulointerstitial abnormalities in the biopsy. This could not be shown for the severity of glomerular pathology by semiquantitative methods. The relation between renal function and glomerular pathology was therefore evaluated in patients with various kidney diseases using quantitative measurements. Fifty-five patients and ten controls were studied. Histomorphometric measurements of renal biopsies were obtained for both frozen and paraffin sections and were correlated with serum creatinine values. The frozen sections were stained with an indirect immunoperoxidase technique using antibodies against collagen types I, IV, V, VI, laminin, fibronectin, decorin and heparansulphate proteoglycan core protein. The contribution of each component to the composition of the mesangial extracellular matrix was scored with a semiquantitative technique. All glomerular histomorphometric indices correlated with the severity of renal insufficiency expressed as serum creatinine at the time of biopsy. However, quantitative estimates of the glomerular deposition of periodic acid-Schiff positive extracellular matrix seemed to be the most important structural correlate of renal function (r = 0.524, p = 0.0001). Semiquantitative estimates of interstitial extracellular matrix accumulation were less correlated with renal function (r = 0.370, p = 0.01). The composition of the mesangial extracellular matrix did not differ in patients and controls, with the exception of the extent of laminin staining, which was significantly higher in patients. The extent of fibronectin staining in patients correlated with the severity of glomerular structural abnormalities. This study demonstrates that the severity of renal insufficiency in a variety of renal diseases correlates with the severity of glomerular pathology, when quantitative scoring is applied.


Subject(s)
Creatinine/blood , Kidney Diseases/pathology , Kidney Glomerulus/chemistry , Kidney Glomerulus/pathology , Adult , Aged , Biopsy , Child, Preschool , Collagen/analysis , Decorin , Extracellular Matrix/chemistry , Extracellular Matrix Proteins , Female , Fibronectins/analysis , Heparitin Sulfate/analogs & derivatives , Heparitin Sulfate/analysis , Humans , Immunohistochemistry , Laminin/analysis , Male , Middle Aged , Periodic Acid-Schiff Reaction , Proteoglycans/analysis
12.
Clin Nephrol ; 44(4): 211-9, 1995 Oct.
Article in English | MEDLINE | ID: mdl-8575119

ABSTRACT

The degree of impairment of renal function in patients with chronic renal failure correlates closely with the extent of fibrosis in the tubulointerstitium, i.e. of interstitial extracellular matrix (ECM) accumulation. The composition of this pathological extracellular matrix and the relation between the ECM composition on the one hand and the severity of histological changes and renal function on the other has not been investigated. This prompted us to perform the present study. The severity of histological abnormalities and the composition of the interstitial ECM were assessed using a semiquantitative scoring technique in 57 biopsies from patients with kidney disease of diverse etiology and variable degrees of renal failure and were contrasted with the results of 9 control biopsies. Tissue sections were stained with an indirect immunoperoxidase technique using antibodies against collagen I, III, IV, V, VI, laminin, fibronectin, decorin and heparansulphate proteoglycan core protein (HSPG). Collagen IV, laminin and HSPG were virtually absent from the interstitium in controls. These components were more widely distributed in patients and the extent of their deposition correlated with the severity of interstitial histological abnormalities. In patients with severe interstitial damage the deposition became diffuse. Collagen type I and III were already diffusely distributed in the interstitium of controls and did not increase significantly as interstitial damage became more severe. However, the extent of collagen III staining in patients was significantly higher than in controls. Decorin staining showed a patchy distribution both in patients and controls. The overall distribution was significantly increased in patients. The extent of the deposition of both collagen V and VI was significantly increased in patients when compared with controls. Only the distribution of collagen V correlated with the severity of histological abnormalities. Our findings suggest that an increased interstitial deposition of extracellular matrix substances which are generally regarded as basement membrane components contributes more to the development of interstitial fibrosis and renal failure than the deposition of the fiber forming interstitial collagens type I and III, which are prominent in controls and in patients irrespective of the severity of histological abnormalities. Decorin staining was significantly enhanced in patients and was found to be the best predictor both of the severity of interstitial fibrosis and of renal failure. This could mean that decorin is important in human renal pathology. Collagen V and VI staining was significantly increased in patients when compared with controls. To our knowledge this is the first study in which this is demonstrated.


Subject(s)
Basement Membrane/pathology , Extracellular Matrix Proteins/metabolism , Extracellular Matrix/pathology , Kidney Diseases/pathology , Proteoglycans/metabolism , Adult , Aged , Analysis of Variance , Basement Membrane/metabolism , Biopsy , Chronic Disease , Collagen/metabolism , Decorin , Disease Progression , Extracellular Matrix/metabolism , Female , Fibrosis/metabolism , Fibrosis/pathology , Humans , Immunohistochemistry , Kidney Diseases/metabolism , Male , Middle Aged , Retrospective Studies
14.
Clin Rheumatol ; 3(3): 305-9, 1984 Sep.
Article in English | MEDLINE | ID: mdl-6488708

ABSTRACT

A self-administered health-assessment questionnaire (HAQ) was completed by 38 Dutch rheumatoid arthritis (RA) patients and the results compared to those obtained objectively when the same subjects were interviewed and asked to perform standardised tasks included in the HAQ. The results of the interview and the questionnaire showed a high degree of overall correlation and inter-component correlation. The correlation was comparable in outpatients with milder disease and in patients with more severe disease and was not influenced by age. The questionnaire offers a valid approach to the assessment of the functional disability of RA patients.


Subject(s)
Arthritis, Rheumatoid/physiopathology , Disability Evaluation , Adult , Aged , Arthritis, Rheumatoid/psychology , Female , Humans , Interviews as Topic , Male , Middle Aged , Netherlands , Self Disclosure , Surveys and Questionnaires
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