Acute hantavirus infection presenting as haemolytic-uraemic syndrome (HUS): the importance of early clinical diagnosis.

The European prototype of hantavirus, Puumala virus (PUUV), isolated from a common wild rodent, the bank vole (Myodes glareolus), causes nephropathia epidemica (NE). NE can perfectly mimic haemolytic-uraemic syndrome (HUS), progressing from an aspecific flu-like syndrome to acute kidney injury with thrombocytopaenia, and presenting with some signs of haemolytic anaemia and/or coagulopathy. Moreover, both NE and HUS can occur in local outbreaks. We report an isolated case of NE, initially referred for plasmapheresis for suspected HUS, although signs of overt haemolysis were lacking. Early suspicion of hantavirus infection, later confirmed by serology and reverse transcription polymerase chain reaction (RT-PCR), prevented subsequent excessive treatment modalities.

Impact of a standardized nurse observation protocol including MEWS after Intensive Care Unit discharge.

BACKGROUND: Analysis of in-hospital mortality after serious adverse events (SAE's) in our hospital showed the need for more frequent observation in medical and surgical wards. We hypothesized that the incidence of SAE's could be decreased by introducing a standard nurse observation protocol. AIM: To investigate the effect of a standard nurse observation protocol implementing the Modified Early Warning Score (MEWS) and a color graphic observation chart. METHODS: Pre- and post-intervention study by analysis of patients records for a 5-day period after Intensive Care Unit (ICU) discharge to 14 medical and surgical wards before (n=530) and after (n=509) the intervention. RESULTS: For the total study population the mean Patient Observation Frequency Per Nursing Shift (POFPNS) during the 5-day period after ICU discharge increased from .9993 (95% C.I. .9637-1.0350) in the pre-intervention period to 1.0732 (95% C.I. 1.0362-1.1101) (p=.005) in the post-intervention period. There was an increased risk of a SAE in patients with MEWS 4 or higher in the present nursing shift (HR 8.25; 95% C.I. 2.88-23.62) and the previous nursing shift (HR 12.83;95% C.I. 4.45-36.99). There was an absolute risk reduction for SAE's within 120h after ICU discharge of 2.2% (95% C.I. -0.4-4.67%) from 5.7% to 3.5%. CONCLUSION: The intervention had a positive impact on the observation frequency. MEWS had a predictive value for SAE's in patients after ICU discharge. The drop in SAE's was substantial but did not reach statistical significance.

Cost analysis in favor of a combined approach for cytomegalovirus after kidney transplantation: a single-center experience.

BACKGROUND: In kidney transplant recipients, cytomegalovirus (CMV) can cause significant morbidity, mortality, and costs, which can be prevented by universal antiviral prophylaxis or preemptive therapy. METHODS: With the aim to improve our understanding of the advantages and disadvantages of these interventions, we documented resource use for 101 consecutive kidney transplant recipients in our center receiving preemptive therapy and estimated resource use for 2 alternative scenarios. RESULTS: At 100 days after transplantation, the mean total costs of our preemptive strategy including monitoring and treatment with intravenous ganciclovir was €2545 per patient. At €4853 per patient, these costs were highest for the CMV-positive donor/CMV-negative recipient (D+/R-) patient subgroup (n = 28), who frequently require recurrent treatment. A treatment scenario with valganciclovir prophylaxis for D+/R- and R+ patients, in which we ignored late-onset disease after discontinuation of prophylaxis, resulted in an estimated cost of €1892 per patient. A combined approach using valganciclovir prophylaxis in the D+/R- group and a preemptive strategy in the R+ groups would result in the lowest mean and median costs per patient (€1701). CONCLUSION: Our study suggests that a combined approach, using valganciclovir prophylaxis in D+/R- patients and preemptive treatment in R+ patients, may result in the lowest cost. This approach seems reasonable as it restricts expensive prophylactic drug therapy to those who would benefit the most, whereas it limits the risk for drug toxicity and late-onset disease in those at lower risk for CMV.

Identification of modifiable risk factors for acute kidney injury after cardiac surgery.

OBJECTIVES: Acute kidney injury (AKI) is a common problem after cardiac surgery and is associated with an increase in morbidity, mortality and duration of hospital stay. With this study we aimed to identify potential risk factors for cardiac surgery associated AKI (CS-AKI) in a single-centre population with a special focus on modifiable risk factors. METHODS: Retrospective single-centre cohort study of 565 consecutive patients who underwent isolated coronary artery bypass grafting (CABG) with the use of cardiopulmonary bypass. AKI was defined by the AKIN classification. Known risk scores were applied when possible. RESULTS: Of the population, 14.7% were diagnosed with AKI. When considering baseline characteristics we found a significant difference in age, preoperative estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) stage and urgency of surgery between the CS-AKI group and the control population. Regarding the intraoperative characteristics, patients with CS-AKI had a significantly lower haematocrit and were more likely to receive a transfusion of packed cells. Postoperative administration of furosemide and packed cell transfusions were also associated with AKI. We found no differences in other characteristics (history of diabetes mellitus, history of congestive heart failure, sex, body mass index (BMI), history of cardiac surgery, low cardiac output and need for intra-aortic balloon pump (IABP), duration of cardiopulmonary bypass (CPB) and cross clamping). CONCLUSION: In our series we could identify intraoperative administration of packed cells and postoperative administration of furosemide or packed cells as potentially modifiable risk factors in the development of AKI.

A four-gene methylation marker panel as triage test in high-risk human papillomavirus positive patients.

Cervical neoplasia-specific biomarkers, e.g. DNA methylation markers, with high sensitivity and specificity are urgently needed to improve current population-based screening on (pre)malignant cervical neoplasia. We aimed to identify new cervical neoplasia-specific DNA methylation markers and to design and validate a methylation marker panel for triage of high-risk human papillomavirus (hr-HPV) positive patients. First, high-throughput quantitative methylation-specific PCRs (QMSP) on a novel OpenArray™ platform, representing 424 primers of 213 cancer specific methylated genes, were performed on frozen tissue samples from 84 cervical cancer patients and 106 normal cervices. Second, the top 20 discriminating methylation markers were validated by LightCycler® MSP on frozen tissue from 27 cervical cancer patients and 20 normal cervices and ROCs and test characteristics were assessed. Three new methylation markers were identified (JAM3, EPB41L3 and TERT), which were subsequently combined with C13ORF18 in our four-gene methylation panel. In a third step, our methylation panel detected in cervical scrapings 94% (70/74) of cervical cancers, while in a fourth step 82% (32/39) cervical intraepithelial neoplasia grade 3 or higher (CIN3+) and 65% (44/68) CIN2+ were detected, with 21% positive cases for ≤CIN1 (16/75). Finally, hypothetical scenario analysis showed that primary hr-HPV testing combined with our four-gene methylation panel as a triage test resulted in a higher identification of CIN3 and cervical cancers and a higher percentage of correct referrals compared to hr-HPV testing in combination with conventional cytology. In conclusion, our four-gene methylation panel might provide an alternative triage test after primary hr-HPV testing.

Antihypertensive effectiveness of aliskiren for the 'real-world' management of hypertension: multilevel modelling of 180-day blood pressure outcomes (the Belgian DRIVER Study).

AIMS: The 'DRIVER' study was designed to investigate the 'real-world' effectiveness of aliskiren-based treatment of hypertension. This article reports the 180-day blood pressure (BP) outcomes, and the multilevel (physician- and patient-level) determinants thereof. METHODS AND RESULTS: DRIVER was a prospective, observational, open-label, multi-centre, pharmaco-epidemiologic study of hypertensive patients treated with aliskiren in whom prior treatment failed or was not tolerated. 2070 patients (enrolled by 426 physicians) were enrolled; 1695 patients (81.9%) completed the 180-day aliskiren treatment period. Mean patient age was 64.2 ± 12.1 years; 53.7% were men, 25.3% diabetic and 40.7% had a high or very high cardiovascular (CV) risk. At 180 days, the mean ± SD reductions in systolic and diastolic BP were -22.9 ± 16.7 mmHg and -10.5 ± 10.9 mmHg respectively (both p < .001). 2007 and 2009 guideline-defined BP control was achieved in 36.4% and 56.3% of patients, respectively (both p < .001). 64.2% of eligible patients had a reduction in CV risk (p < .001). A physician-level class effect was responsible for 22.8% and 28.1% of variability in systolic and diastolic BP, respectively, for 20.1% of variability in BP control, and for 16.1% of variability in the reduction of CV risk. Both patient- (e.g. adherence) and physician-related factors (e.g. age and knowledge) were significant in profiling best response to treatment with aliskiren. Adverse events reported in this article were consistent with the aliskiren scientific leaflet. CONCLUSION: Aliskiren is safe and effective in reducing BP, improving BP control and reducing global CV risk in a 'real-world' setting and for patients in whom prior treatment failed or was not tolerated. Optimising treatment adherence and strategic medical education may be ways of improving BP outcomes in patients with hypertension.

Prevalence of chronic renal failure stage 3 or more in HIV-infected patients in Antwerp: an observational study.

The introduction of Highly Active Antiretroviral Therapy has transformed HIV-infection from an inevitably lethal disease to a chronic condition with a life expectancy comparable to that of people with diabetes mellitus. In recent years it has become evident that people living with HIV/AIDS have an increased risk of developing cardiovascular disease and it is expected that the prevalence of chronic kidney disease will rise accordingly. To investigate the prevalence of chronic kidney disease in patients with HIV, we conducted a retrospective observational analysis using the clinical database of a large centre (Institute of Tropical Medicine) in the urban area of Antwerp, Belgium. The prevalence of chronic kidney disease among HIV infected subjects was found to be 3.0%. The development of chronic kidney disease was associated with age above 50 years, lower CD4 cell counts and Caucasian origin. Screening for chronic renal disorders and prevention of evolution toward chronic renal failure is a crucial challenge in the management of people living with HIV/AIDS.

Adherence to bisphosphonates therapy and hip fracture risk in osteoporotic women.

UNLABELLED: Adherence is now one of the major issues in the management of osteoporosis and several papers have suggested that vertebral fractures might be increased in patients who do not follow appropriately their prescriptions. This paper relates the strong relationship existing between adherence to anti-osteoporosis treatment and the risk of subsequent hip fracture. INTRODUCTION: A study was performed to investigate adherence to bisphosphonate (BP) therapy and the impact of adherence on the risk of hip fracture (Fx). METHODS: An exhaustive search of the Belgian national social security database was conducted. Patients enrolled in the study were postmenopausal women, naive to BP, who received a first prescription of alendronate. Compliance at 12 months was quantified using the medication possession ratio (MPR). Persistence was calculated as the number of days from the initial prescription to a gap of more than 5 weeks after completion of the previous refill. A logistic regression model was used to estimate the impact of compliance on the risk of hip fracture. The impact of persistence on hip fracture risk was analysed using the Cox proportional hazards model. RESULTS: The mean MPR at 12 months was significantly higher among patients receiving weekly (n = 15.021) compared to daily alendronate (n = 14,136) (daily = 58.6%; weekly = 70.5%; p < 0.001). At 12 months, the rate of persistence was 39.45%. For each decrease of the MPR by 1%, the risk of hip Fx increased by 0.4% (OR: 0.996; CI 95%: 0.994-0.998; p < 0.001). The relative risk reduction for hip Fx was 60% (HR: 0.404; CI 95%: 0.357-0.457; p < 0.0001) for persistent compared to non-persistent patients. CONCLUSION: These results confirm that adherence to current therapeutic regimens remains suboptimal.

Malignancy after kidney transplantation: still a challenge.

Long-term complications of continuous immunosuppression still remain a serious threat and are currently drawing the attention of transplant physicians. Wimmer et al. show that malignancy occurs approximately fourfold more frequently in renal-transplant recipients than in a normal control population. Besides immunosuppression, viruses probably play an important oncogenic role in transplant recipients. The retrospective analysis by Wimmer et al. suggests that mTOR inhibitors and interleukin-2 receptor antibodies are promising immunosuppressive drugs to reduce the risk of cancer after transplantation. These preliminary results must be confirmed in large, prospective, randomized, controlled trials, with long follow-up, designed to evaluate the incidence of de novo malignancy in transplant recipients.

Lipid and apoprotein changes during atorvastatin up-titration in hemodialysis patients with hypercholesterolemia: a placebo-controlled study.

BACKGROUND: Patients with end-stage renal disease commonly present with an atherogenic lipid profile characterized by the accumulation of triglyceride-rich, apoprotein B-containing "remnant" lipoproteins, small dense low-density lipoprotein, and low levels of high-density lipoprotein. They are at increased cardiovascular risk and may benefit from drastic lipid-lowering treatment with atorvastatin, a potent, broadacting lipid regulator. This study aims to assess the effects of atorvastatin on the lipid profile in hemodialysis patients, to determine wether atorvastatin is also effective at lowering lipid levels in this particular high-risk subgroup. METHODS: In this randomized, placebo-controlled, double-blind study in hemodialysis patients with hypercholesterolemia (n = 42, mean total cholesterol 243 +/- 33 mg/dl (6.3 +/- 0.8 mmol/l)), the efficacy of 4-weekly increasing doses of atorvastatin (10 - 40 mg daily) was investigated. Lipids and apoproteins were measured in plasma and isolated lipoprotein fractions. RESULTS: Mean total cholesterol and low-density lipoprotein cholesterol progressively decreased with increasing doses of atorvastatin (total cholesterol -33%, low-density lipoprotein cholesterol -43% after 12 weeks), while high-density lipoprotein cholesterol remained unchanged. Plasma levels of apoprotein B and apoprotein E were also significantly reduced by atorvastatin 10 mg, while up-titration to 20 and 40 mg daily provided additional benefits by lowering triglycerides and apoprotein C-III. At week 12, the fraction of small dense low-density lipoprotein was significantly reduced from 23% - 18%, and apoprotein B-containing intermediate-density lipoproteins were no longer detectable. CONCLUSION: In conclusion, atorvastatin not only treated hypercholesterolemia but also favorably affected the uremic lipid profile in patients on hemodialysis. Atorvastatin 4-weekly dose escalation up to 40 mg daily was well-tolerated. Further prospective studies are needed to evaluate the impact of this improved lipid profile on morbidity and mortality.

Four cases of red blood cell aplasia in association with the use of mycophenolate mofetil in renal transplant patients.

Mycophenolate mofetil (MMF) is one of the new immunosuppressive drugs used in renal transplantation. MMF inhibits the de novo purine synthesis. Since this purine synthesis in lymphocytes entirely depends on the de novo pathway, MMF is considered to cause a selective inhibition of T- and B lymphocytes. Recently, 4 transplant patients out of 30 developed a severe anemia in the early post-transplantation period. Their immediate post-transplantation immunosuppression consisted of corticosteroids, cyclosporine and MMF. They all received anti-T-lymphocyte globulin (ATG) as induction treatment or because of rejection. In all 4 patients, iron supplementation and a treatment with erythropoietin were started. Blood loss, deficiencies, hemolysis, drug interactions or viral infections were excluded as causes of the anemia. Bone marrow biopsies were carried out, showing pure red cell aplasia that was ascribed to the use of MMF. Cessation or reduction of MMF was followed by a hematological improvement after 5-9 days. We hypothesized that MMF has a broader antiproliferative effect than its proposed lymphocyte-specific effect.

Stability of far field R wave signals in different conditions.

AIMS: The presence of far field R wave sensing (FFRS) is usually evaluated in patients with dual chamber pacemakers in supine position. To check if this approach is valid, we tested whether FFRS is consistent both in terms of amplitude threshold and timing characteristics in different daily life conditions. METHODS AND RESULTS: In 42 patients with a DDD pacemaker, the presence, amplitude threshold and timing parameters of FFRS were therefore determined, with patients supine, standing and at peak exercise. Measurements were made of paced and sensed R waves, in unipolar and bipolar sensing configurations (at peak exercise only paced R waves and bipolar sensing). After paced R waves (bipolar sensing) amplitude thresholds/time of FFRS after V pace were 0.32+/-0.18 mV/119-139 ms (supine), 0.32+/-0.16 mV/114-130 ms (upright) and 0.27+/-0.13 mV/121-136 ms (exercise) - with unipolar sensing, this was 0.49+/-0.27 mV/101-150 ms (supine), 0.51+/-0.29 mV/100-144 ms (upright). After sensed R waves (bipolar sensing) amplitude thresholds/time of FFRS after V sense were 0.27+/-0.18 mV/24-42 ms (supine), 0.29+/-0.16 mV/18 to 41 ms (upright) - with unipolar sensing, thresholds were 0.59+/-0.32 mV/3-50 ms (supine), 0.59+/-0.36 mV/2-58 ms (upright). CONCLUSION: given the lower FFRS thresholds with bipolar sensing, bipolar sensing is superior in avoiding FFRS compared with unipolar sensing. No differences were found in terms of amplitude thresholds and timing characteristics with patients supine, standing and at peak exercise. Thus, measurements made in the supine position are basically sufficient to predict the presence/absence of FFRS under different conditions.

Oxidative modification of low-density lipoproteins and the outcome of renal allografts at 1 1/2 years.

BACKGROUND: Previous studies reported a significant association between hyperlipidemia of the recipient and chronic allograft nephropathy (CAN). However, the nature and the pathogenic mechanism of circulating lipid abnormalities in CAN remain unclear. METHODS: In a prospective study of 50 consecutive adult recipients of a cadaveric renal allograft, we investigated the impact of lipid abnormalities on the outcome of the graft at 1 1/2 years. Besides morphometric analysis of implantation and protocol biopsies, clinical and biochemical variables were studied at three-month intervals. Plasma concentrations of oxidized low-density lipoprotein (OxLDL) were determined by means of enzyme-linked immunosorbent assay. Immunohistochemical staining for OxLDL and macrophages was performed on paired renal biopsies. Study end points were the fractional interstitial volume and the 24-hour creatinine clearance at 11/2 years. RESULTS: High-density lipoprotein (HDL) cholesterol of the recipient < or =47 mg/dL was a risk factor for the functional (RR = 1.56; 95% CI, 0.978 to 2.497) and the morphological (RR = 2.75; 95% CI, 1.075 to 7.037) outcome of the graft, mainly in patients without acute rejection (RR = 2.03; 95% CI, 1.13 to 3.65, and RR = 4.67; 95% CI, 1.172 to 18.582, respectively). Interstitial accumulation of OxLDL was inversely associated with HDL cholesterol (R = -0.476, P = 0.019), and was associated with a higher density of tubulointerstitial macrophages (R = 0.656, P = 0.001) and a higher fractional interstitial volume at 11/2 years (P = 0.049). CONCLUSION: Decreased HDL cholesterol levels of the recipient adversely affect the outcome of renal allografts through the accumulation of OxLDL in the renal interstitium of the graft. Interstitial accumulation of OxLDL was associated with the presence of macrophages and the development of interstitial fibrosis.

Identification and kinetics of leukocytes after severe ischaemia/reperfusion renal injury.

BACKGROUND: Leukocyte adhesion/infiltration in response to renal ischaemia/reperfusion (I/R) injury is a well-known but poorly understood phenomenon. The identification, kinetics, and exact role of these inflammatory cells in I/R injury and regeneration are still matters of debate. METHODS: Uninephrectomized rats were submitted to 60 min renal ischaemia by clamping of renal vessels. RESULTS: Severe acute renal failure was observed, with maximum functional impairment on day 2. By 12 h after the ischaemic event, up to 80% of proximal tubular cells in the outer stripe of outer medulla (OSOM) were already severely damaged. Proliferation (proliferating cell nuclear antigen (PCNA) staining) started after 24 h, reaching maximum activity on day 3. Regeneration of tubular morphology started on the 3rd day, and after 10 days 50% of tubules had regenerated completely. Interstitial leukocytes (OX-1 immunohistochemical staining) were already prominent at day 1, thereafter gradually increasing with time. The so-called neutrophil-specific identification methods (myeloperoxidase (MPO), chloroacetate esterase, mAb HIS-48) proved to be non-specific, since they also stained for macrophages, as demonstrated by flow cytometry and the combination of these stainings with the macrophage-specific ED-1 staining. MPO activity was already significantly increased at 1 h post-I/R (439+/-34%, P<0.005), reaching its maximum activity after 12 h of I/R (1159+/-138%, P<0.0005), declining thereafter. On the other hand, neutrophil presence investigated by H&E staining revealed only a few neutrophils in glomeruli, medullary rays, and OSOM at 24 h after the ischaemic event (4.7+/-4.2 cells/mm(2) vs controls=2.3+/-2.0 cells/mm(2) (n.s.)), and remained unchanged over the next 10 days. In contrast, significant monocyte/macrophage adhesion/infiltration (ED-1 staining) occurred at the OSOM at 24 h post-ischaemia (at 24 h, 120+/-46 cells/mm(2) vs. sham=18+/-4 cells/mm(2) (P<0.05)), became prominent at day 5 (1034+/-161 cells/mm(2) vs sham=18+/-18 cells/mm(2) (P<0.05)), and almost disappeared after 10 days. CD4(+) cells (W3/25) gradually increased from day 5, reaching a maximum at day 10. A few CD8(+) cells (OX-8) were apparent from days 3 until 10, but no B-cells (OX-33) were observed. CONCLUSIONS: After severe warm I/R renal injury, a pronounced acute tubular necrosis occurs during the first 12-24 h in the absence of a marked cellular infiltrate, but with an important renal MPO activity, reflecting the activation of the adhering inflammatory cells (polymorphonuclear cells (PMNs) and mainly monocytes/macrophages). Only later at the time and site (OSOM) of regeneration a sequential accumulation of monocytes/macrophages and T cells becomes prominent, in contrast with the low number of neutrophils found in the kidney during the 10-day post-ischaemic period. The non-specificity of the so-called neutrophil-specific identification methods (MPO activity, naphthol AS-D chloroacetate esterase, or mAb HIS-48 staining), cross-reacting with monocytes/macrophages, explains the controversy in literature concerning the number of PMNs in post-ischaemic injury.

TIMP-1 gene expression and PAI-1 antigen after unilateral ureteral obstruction in the adult male rat.

BACKGROUND: Sustained obstruction of urinary flow invariably leads to inflammation, loss of functional renal structures and progressive deposition of extracellular matrix proteins, culminating in renal fibrosis. Although increased renal tissue inhibitor of matrix metalloproteinase (TIMP-1) expression is one of the early events following experimental hydronephrosis, little is known about its cellular source. Both the recruited macrophage and the resident/recruited (myo)fibroblast have been postulated to be candidate TIMP-1 transcribing cells. Currently, data concerning plasminogen activator inhibitor type 1 (PAI-1) expression in the ligated kidney are unavailable. Our study concentrated on the localization of TIMP-1 expressing cells and PAI-1 immunoreactive cells in the obstructed rat kidney. METHODS: Rats were sacrificed 1, 5, 10, 15, 20 and 26 days after unilateral ureteral obstruction (UUO) or sham-surgery (SOR). Leukocyte (OX-1+), macrophage (ED1+) and neutrophil infiltration were analyzed using specific antibodies or nuclear morphology. alpha-Smooth muscle actin (alpha-SMA) immunostaining was measured morphometrically. Mitotic figures and nuclei with an apoptotic morphology were quantified in hematoxylin-eosin (H&E)-stained sections. TIMP-1 mRNA transcribing cells were localized with in situ hybridization (ISH) and identified by subsequent immunostainings for alpha-SMA and macrophages. PAI-1 antigenicity was evaluated immunohistochemically in SOR, contralateral unobstructed kidneys (CUK), and UUO kidneys. RESULTS: The number of leukocytes and macrophages in the ligated rat kidney increased progressively in time, starting from day 5 post-surgery when compared with CUKs. Neutrophil accumulation in UUO kidneys became apparent from day 5 and large intraluminal leukocyte clusters (neutrophils and macrophages) were found in the lumen of distended tubules, especially at later stages post-obstruction, when collected urine and tissue samples proved to be sterile upon culture. From day 5 on, the number of apoptotic cells started to predominate the number of mitotic cells in the obstructed kidneys. Interstitial alpha-SMA immunoreactivity in the ligated kidney expanded from day 5 on and was most pronounced in the inner stripe of the outer medulla. As early as 24 hours post-ligation, TIMP-1 mRNA transcribing interstitial cells were detected with ISH, while tubular TIMP-1 expression was sparse. Since at that point in time, no interstitial alpha-SMA expressing cells and only few ED1+ macrophages were present, the bulk of the TIMP-1 mRNA transcription occurred in other interstitial cells. Throughout the study period numerous interstitial TIMP-1 expressing cells were detectable in obstructed kidneys and from day 5 after ligation on, we could identify alpha-SMA+ and to a lesser degree ED1+ macrophages as TIMP-1 transcribing cells. In addition, dilated tubules containing intraluminal leukocyte casts were surrounded by a corona of intact neutrophils in H&E-stained sections and ISH showed that similar tubules were encircled by TIMP-1 mRNA expressing cells. PAI-1 immunoreactivity appeared to diminish in the early phase following urinary outlet obstruction, but emerged in damaged tubules from day 5 to 10 on. In later stages post-ligation, PAI-1+ cells and PAI-1 immunoreactive material were found embedded in the extracellular matrix. CONCLUSIONS: Our results confirm that TIMP-1 is active in the early phase of the fibrotic process and we demonstrated that initially TIMP-1 mRNA is transcribed by very few ED1+ macrophages but mainly by other, presently unidentified, interstitial cells. During later stages of post-ligation, both TIMP-1 (transcribed among others by alpha-SMA+ myofibroblasts, ED1+ macrophages, and possibly neutrophils) and PAI-1 are involved in the progression of tubulointerstitial scarring.

Morphometric analysis of renal vessels. Advantage of the multisector area approach to cross-sections.

OBJECTIVE: To determine the most accurate morphometric approach to overcoming the obstacles of limited number, angle of section and irregular contours of vascular structures in analyzing vascular sections of renal biopsies. STUDY DESIGN: The luminal area of 451 cortical arterioles in 65 Masson-trichrome-stained renal sections was assessed with a computer-assisted imaging system connected to a Leica DMR microscope (Mikroskopie und Systeme GmbH, Wetzlar, Germany). The luminal area measured by the imaging system was used as the gold standard, against which three mathematical sector approaches and one classical approach were evaluated. The accuracy of these approaches was evaluated by means of the relative deviation from the measured value and of the degree of overestimation or underestimation. Intraobserver and interobserver variability were determined for the most accurate mathematical approach. RESULTS: As compared to measured luminal area, the sector elliptical approach yielded the lowest relative deviation (13.4 +/- 12.5%), without significant overestimation or underestimation (-0.6 +/- 18.3%). The intraobserver and interobserver correlation coefficients for this method were 82.3% and 86.5%, respectively. CONCLUSION: The sector elliptical approach is the most accurate mathematical approach to vascular sections in renal biopsies.

Treatment of bone and joint infections: recommendations of a Belgian panel.

A multidisciplinary panel of Belgian specialists describes the overall therapeutic approach for bone and joint infections. Classification, general methods of investigation, therapeutic options, special circumstances, the role of aminoglycosides and of glycopeptides are described. The possibility of home treatment is discussed, as well as some pharmaco-economic insights.