[Current dilemmas on the transmission of hepatitis E virus]. / Actuele dilemma's rond de transmissie van hepatitis E-virus.

Immunocompromised patients are especially at risk for developing chronic hepatitis E virus (HEV) infection, which may result in progressive liver disease and cirrhosis. In addition, treatment of chronic HEV infection in these patients often includes dose reduction of immunosuppressive therapy and this may lead to severe flare-ups of the underlying condition or even rejection of transplant material. Therefore prevention of HEV transmission is being more and more recognised as an essential step to stop increasing HEV seroprevalence. The Dutch National Institute for Public Health and the Environment (RIVM) has recently warned immunocompromised patients following haematopoietic stem cell and solid organ transplantations for the risk of infection by HEV through eating of contaminated products from pig meat. Furthermore, the Dutch blood bank recently decided to start screening all blood products for HEV to prevent iatrogenic transmission of HEV. We describe two patients with HEV infection and discuss risk of infection for immunocompromised patients, transmission routes and the importance of prevention of iatrogenic transfusion related transmission.

Relationships of body habitus and SUV indices with signal-to-noise ratio of hepatic (18)F-FDG PET.

OBJECTIVE: Tissue accumulation of (18)F-FDG is quantified as standardised uptake value (SUV), which may be expressed as the voxel maximum (SUVmax) or mean (SUVmean). SUVmax/SUVmean may be a marker of hepatic steatosis, while the coefficient of variation (CV) of SUV may be a marker of hepatic fat distribution heterogeneity (HFDH). Alternatively, they may reflect low signal-to-noise ratio ('noise') in obese persons in whom hepatic steatosis is common. The study aim was to compare the impact of body size on noise versus SUV and CT density (CTD). METHODS: Dynamic PET was performed (30×1min frames) following FDG injection in 60 patients undergoing routine PET/CT. Hepatic FDG clearance was measured using Patlak-Rutland graphical analysis with abdominal aorta as input. Noise was quantified as the standard deviation (SD) of the plot residuals (ignoring the first 2 frames), normalised to the intercept (NRMSD). SUVmax, SUVmean and CTD were measured from 60min whole body PET/CT. CV of SUV and SD of CTD were quantified in 28/60 patients using texture analysis. RESULTS: NRMSD correlated with weight (r=0.49; p<0.0001) and BMI (r=0.48; p=0.0001). SUVmax, SUVmean, SUVmax/SUVmean, CV of SUV, CTD, and SD of CTD all correlated strongly with weight and BMI (p<0.0001). However, they correlated weakly with NRMSD, the strongest being SUVmax (r=0.34; p=0.008) and SD of CTD (r=0.42; n=28; p=0.026). CONCLUSIONS: Noise is increased in overweight/obese persons but has little effect on SUV indices, CTD and their variabilities. SUVmax/SUVmean and CV of SUV are therefore, to some extent, markers of hepatic steatosis and HFDH, respectively.

The appropriate whole-body index on which to base standardized uptake value in 2-deoxy-2-[(18)F]fludeoxyglucose PET.

OBJECTIVE: Tissue uptake of 2-deoxy-2-fluorine-18 fludeoxyglucose ((18)F-FDG) is routinely quantified as standardized uptake value (SUV), which in general is the fraction (F) of administered activity per millilitre of tissue multiplied by an index of body size, usually weight (W), i.e. F/ml × W = SUV or F/ml = SUV × (1/W). Other indices have been suggested as preferable to W, especially lean body mass (LBM) and body surface area (BSA). The second equation mentioned above shows that the reciprocal of the ideal index should correlate closely with F/ml and give a regression line through the origin. The purpose of this study was to determine which of these three indices best meets these criteria. METHODS: Data were evaluated from 49 males and 51 females undergoing routine (18)F-FDG positron emission tomography/CT. A 3 cm diameter region of interest was drawn over the liver and F/ml recorded. LBM and BSA were estimated from height and weight. RESULTS: Based on all patients, the reciprocals of the three indices gave similar correlation coefficients with F/ml, but only 1/LBM gave regressions close to the origin. Intercepts were significantly higher for females for 1/W and 1/BSA, consistent with females having more body fat, but there was no significant difference with 1/LBM. CONCLUSION: LBM is the best index on which to base SUV because adipose tissue accumulates less (18)F-FDG than other soft tissues. ADVANCES IN KNOWLEDGE: The value of this study lies in its use of a novel, more rational approach than previously to confirm that SUV should be based on LBM.

Adjuvant taxanes and the development of breast cancer-related arm lymphoedema.

BACKGROUND: Despite affecting approximately one-quarter of all patients undergoing axillary lymph node dissection, the pathophysiology of breast cancer-related lymphoedema (BCRL) remains poorly understood. More extensive locoregional treatment and higher body mass index have long been identified as major risk factors. This study aimed to identify risk factors for BCRL with a specific focus on the potential impact of chemotherapy on the risk of BCRL. METHODS: This was a retrospective analysis of a cohort of consecutive patients with breast cancer treated at a major London regional teaching hospital between 1 January 2010 and 31 December 2012. All patients had node-positive disease and underwent axillary lymph node dissection. Data regarding tumour-, patient- and treatment-related characteristics were collected prospectively. The diagnosis of BCRL was based on both subjective and objective criteria. Multivariable Cox proportional hazards regression was used to assess the association between treatment and risk of BCRL. RESULTS: Some 27.1 per cent of all patients (74 of 273) developed BCRL over the study period. Administration of taxanes showed a strong association with the development of BCRL, as 52 (33.5 per cent) of 155 patients who received taxanes developed BCRL. Multivariable Cox regression analysis demonstrated that patients who received taxanes were nearly three times more likely to develop BCRL than patients who had no chemotherapy (hazard ratio 2.82, 95 per cent c.i. 1.31 to 6.06). No such increase was observed when taxanes were administered in the neoadjuvant setting. CONCLUSION: The present findings suggest that adjuvant taxanes play a key role in the development of BCRL after surgery. This may support the use of taxanes in a neoadjuvant rather than adjuvant setting.

Global abnormalities in lymphatic function following systemic therapy in patients with breast cancer.

BACKGROUND: Breast cancer-related lymphoedema (BCRL) is a result of interaction between several pathophysiological processes, and is not simply a 'stopcock' effect resulting from removal of axillary lymph nodes. The aim of this study was to test the hypothesis that there is a constitutional 'global' lymphatic dysfunction in patients who develop BCRL. METHODS: Lower-limb lymphoscintigraphy was performed in 30 women who had undergone axillary lymph node dissection at least 3 years previously, of whom 15 had BCRL and 15 did not. No patient had any clinical abnormality of the lower limb. The control group comprised 24 women with no history of cancer or lower-limb lymphoedema. (99m) Tc-Nanocoll was injected subcutaneously into the first webspace of each foot, followed by whole-body imaging. Scans were reported as abnormal if there was delay in lymph transport or rerouting through skin or deep system. Quantification was expressed as the percentage injected activity accumulating in ilioinguinal nodes. RESULTS: Mean(s.d.) ilioinguinal nodal accumulation at 150 min was significantly lower in women with BCRL than in those without (2·7(2·5) versus 5·9(4·8) per cent respectively; P = 0·006). Abnormal findings on lower-limb lymphoscintigraphy were observed in 17 of the 30 patients: ten of the 15 women who had BCRL and seven of the 15 who did not. None of the 24 control subjects had abnormal scan findings. CONCLUSION: Women with BCRL had reduced lower-limb lymph drainage, supporting the hypothesis of a predisposition to BCRL. A surprisingly high proportion of patients with breast cancer also demonstrated lymphatic dysfunction, despite clinically normal lower limbs. Possible explanations could be a systemic effect of breast cancer or its treatment, or an unidentified association between breast cancer and lymphatic dysfunction. REGISTRATION NUMBER: ISRCTN84866416 ( http://www.isrctn.com).

Determination of extracellular fluid volume in healthy and azotemic cats.

BACKGROUND: Methods for determining extracellular fluid volume (ECFV) are important clinically for cats. Bromide dilution has been studied in cats to estimate ECFV. Markers of GFR also distribute in ECFV and can be used for its measurement. HYPOTHESIS/OBJECTIVES: The primary objective was to develop a method of determining ECFV from iohexol clearance in cats and evaluate agreement with that determined using bromide dilution. Additional objectives were to compare ECFV between azotemic and nonazotemic cats and evaluate appropriate methods of standardizing ECFV. ANIMALS: Client-owned cats with varying renal function. METHODS: Validation of ECFV determined from slope-intercept iohexol clearance was performed in 18 healthy nonazotemic cats. ECFV was then determined using the validated method and bromide dilution and agreement assessed. Appropriateness of standardization to body weight (BW) and body surface area (BSA) was evaluated. RESULTS: Extracellular fluid volume determined from slope-intercept iohexol clearance and bromide dilution was 0.84 ± 0.32 L and 0.85 ± 0.19 L (mean ± SD), respectively. There were wide limits of agreement between the methods (-0.58 to 0.54 L) and therefore, agreement was considered to be poor. ECFV did not differ significantly between azotemic and nonazotemic cats (P = .177). BSA was found to be the best method for standardizing ECFV measurement in cats. CONCLUSIONS AND CLINICAL IMPORTANCE: This study developed a method for determining ECFV from slope-intercept iohexol clearance which provides simultaneous assessment of renal function and an estimate of ECFV. ECFV does not differ between azotemic and nonazotemic cats, which suggests fluid volume loss or overload is not an important clinical feature in cats with mild chronic kidney disease.

A constitutional predisposition to breast cancer-related lymphoedema and effect of axillary lymph node surgery on forearm muscle lymph flow.

AIM: The aims of this prospective study were (a) to examine the relationship between pre-operative muscle lymph flow and the predisposition to BCRL in women treated by axillary nodal surgery for breast cancer; and (b) to test the 'stopcock' hypothesis that axillary lymph node surgery impairs forearm lymph flow in the short term. METHODS: (99m)Tc-nanocoll was injected intramuscularly into both forearms of women undergoing surgery for breast cancer. Lymphatic clearance rate constant, k, representing lymph flow per unit interstitial fluid volume, was measured as the fractional disappearance rate of radioactivity from the depot site by gamma camera imaging. Axillary lymph node activity was calculated as percentage injected activity. BCRL was assessed by clinical examination and upper limb perometry. RESULTS: Of 38 pre-operative women, 33 attended at 8 ± 6 weeks post-operatively and 31 at 58 ± 9 weeks post-operatively. Seven patients (18%) developed BCRL. Prior to surgery the BCRL-destined patients had a higher mean k (0.0962 ± 0.034%/min) than non-BCRL patients (0.0830 ± 0.019%/min) (p = 0.10, unpaired t test). Post-operative k values were not significantly different from pre-operative, in either the ipsilateral (operated) or contralateral limb. Also, post-operative k values did not differ significantly between both upper limbs. Furthermore, there was no significant difference between pre- and post-operative axillary activity. CONCLUSION: Patients who develop BCRL have high lymph flow pre-surgery, which may predispose them to lymphatic overload and failure. Axillary lymph node surgery has no early, measurable effect on forearm muscle lymph flow despite surgical disruption of routes of lymph drainage.

An investigation of lymphovenous communications in the upper limbs of breast cancer patients.

BACKGROUND: Approximately 25% of breast cancer patients who undergo treatment to the axilla develop breast cancer-related lymphoedema (BCRL). The aim of this study was to test the hypothesis that lymphovenous communications (LVCs) open and act as a protective mechanism against the development of BCRL. METHODS: Five patients (Group 1) received intradermal injections of (99m)Technetium-labelled autologous erythrocytes into the 2nd ipsilateral hand webspace before and 6-12 weeks following axillary node clearance surgery (ANC). Ten patients at least three years after ANC were also recruited (Group 2); seven had developed BCRL and three had not. Blood was sampled from ipsilateral and contralateral antecubital veins 5, 15, 30, 60, 120 and 180 min post-injection to assess pre-nodal shunting from lymph to blood (LVCs), since nodes block erythrocyte transit. The proportion of activity remaining in the depot was used to calculate the degree of shunting in those with evidence of LVCs. RESULTS: Significant erythrocyte-bound activity, increasing over time, was detected contralaterally in 3 of the 5 patients from Group 1 (none of whom developed BCRL) and 3 of 7 patients with BCRL from Group 2, which indicated the presence of LVCs. The degree of shunting was more marked in those patients who did not develop BCRL compared with those who did. CONCLUSIONS: The time-course of erythrocyte-bound contralateral activity indicates transit through lymphovenous communications rather than needle-induced trauma. Lymphovenous communications large enough to transmit erythrocytes are probably constitutional rather than induced. A larger study is warranted to assess any resulting protection against BCRL.

Three-dimensional vessel segmentation using a novel combinatory filter framework.

Blood vessel segmentation is of great importance in medical diagnostic applications. Filter based methods that make use of Hessian matrices have been found to be very useful for blood vessel segmentation in both 2D and 3D medical images. However, these methods often fail on images that contain high density microvessels and background noise. The errors in the form of missing, undesired broken or incorrectly merged vessels eventually lead to poor segmentation results. In this paper, we present a novel method for 3D vessel segmentation that is also suitable for segmenting microvessels, incorporating the advantages of a line filter and a Hessian-based vessel filter to overcome the problems. The proposed method is shown to be reliable for noisy and inhomogeneous images. Vessels can also be separated based on their scale/thickness so that the method can be used for different medical applications. Furthermore, a quantitative vessel analysis method based on the multifractal analysis is performed on the segmented vasculature and fractal properties are found in all images.

A single sample method for estimating glomerular filtration rate in cats.

BACKGROUND: Validated methods of estimating glomerular filtration rate (GFR) in cats requiring only a limited number of samples are desirable. HYPOTHESIS/OBJECTIVES: To test a single sample method of determining GFR in cats. ANIMALS: The validation population (group 1) consisted of 89 client-owned cats (73 nonazotemic and 16 azotemic). A separate population of 18 healthy nonazotemic cats (group 2) was used to test the methods. METHODS: Glomerular filtration rate was determined in group 1 using corrected slope-intercept iohexol clearance. Single sample clearance was determined using the Jacobsson and modified Jacobsson methods and validated against slope-intercept clearance. Extracellular fluid volume (ECFV) was determined from slope-intercept clearance with correction for the 1 compartment assumption and by deriving a prediction formula for ECFV (ECFV Predicted ) based on the body weight. The optimal single sample method was tested in group 2. RESULTS: A blood sample at 180 minutes and ECFV Predicted were optimal for single sample clearance. Mean ± SD GFR in group 1 determined using the Jacobsson and modified Jacobsson formulae was 1.78 ± 0.70 and 1.65 ± 0.60 mL/min/kg, respectively. When tested in group 2, the Jacobsson method overestimated multisample clearance. The modified Jacobsson method (mean ± SD 2.22 ± 0.34 mL/min/kg) was in agreement with multisample clearance (mean ± SD 2.19 ± 0.34 mL/min/kg). CONCLUSIONS AND CLINICAL IMPORTANCE: The modified Jacobsson method provides accurate estimation of iohexol clearance in cats, from a single sample collected at 180 minutes postinjection and using a formula based on the body weight to predict ECFV. Further validation of the formula in patients with very high or very low GFR is required.

Change in Nox4 expression is accompanied by changes in myogenic marker expression in differentiating C2C12 myoblasts.

Myoblast differentiation is mediated by a cascade of changes in gene expression including transcription factors such as myogenin. Subsequent to myoblast differentiation, there is an increase in expression of the transmembrane protein NADPH oxidase (Nox). Nox is one of the primary factors for the generation of reactive oxygen species (ROS) in myogenic (C2C12) cells. Recently, ROS have been shown to be important regulators of several intracellular signaling pathways, and the full extent of their regulatory roles is yet to be discovered. In the present study, qRT PCR analysis demonstrated that Nox4 isoform is primarily expressed in differentiating C2C12 cells and contributes to the generation of ROS in C2C12 myoblast during differentiation. Over-expression and silencing of Nox4 expression during myoblast differentiation was accompanied by a reduction in intracellular ROS concentrations and an alteration in the expression patterns of Myf5, Pax7, MyoD1, and myogenin. This modulation was found to be associated with ERK1/2 phosphorylation. In both over-expression and reduced expression of Nox4, we found significant reductions in ERK1/2 phosphorylation. This indicates that cellular differentiation may be affected by Nox4-mediated endogenous ROS generation. These data suggest a new opportunity to study the temporal expression of Nox4 in the generation of ROS accompanying changes in myogenic differentiation.

A qualitative and quantitative assessment of the impact of three processing algorithms with halving of study count statistics in myocardial perfusion imaging: filtered backprojection, maximal likelihood expectation maximisation and ordered subset expectation maximisation with resolution recovery.

INTRODUCTION: Ordered subset expectation maximisation with depth-dependent resolution recovery (OSEM-RR) is a processing algorithm reported to improve images with halved tracer activity in myocardial perfusion scintigraphy (MPS) compared to filtered backprojection (FBP) using conventional activities. OSEM-RR has not yet been compared with maximal likelihood expectation maximisation (MLEM). METHODS: 39 patients undergoing MPS and two anthropomorphic phantoms (one with, one without an inferior wall insert) had full-time (FT) and half-time (HT) SPECT datasets acquired simultaneously and processed by FBP, MLEM and OSEM-RR. Two experienced reporters scored images of all clinical studies (n=234) for conspicuity of a perfusion defect, with results being compared using Wilcoxon paired and Kappa tests. A quantitative assessment based on mean segmental pixel counts taken from numbers automatically displayed over the 20 segments of Cedars Sinai Autoquant QPS image were compared using Pearson's correlation and Bland Altman analysis. RESULTS: A small but consistent superior concurrence between FT and HT datasets for OSEM-RR compared to FBP and MLEM was observed for both qualitative and quantitative analyses. OSEM-RR resulted in better definition of the inferior wall defect on the phantom study. CONCLUSION: OSEM-RR appears superior to both FBP and MLEM in terms of handling reduced count statistics.

Estimation of lean body mass in children.

BACKGROUND: In adults, dosages of some anaesthetic agents are based on lean body mass (LBM) rather than body weight. Our aim was to derive an equation for estimating LBM in children. METHODS: Patients comprised three groups: prospective kidney transplant donors from two separate centres (centres 1 and 3) and children referred to a further centre (centre 2) for the routine clinical measurement of glomerular filtration rate (GFR). GFR and extracellular fluid volume (ECV) were measured using Cr-51-EDTA. LBM was directly estimated (eLBM) in adults using an equation based on height and weight. ECV in children was estimated (eECV) from another equation based on height and weight, converted to eLBM using the relationship between eLBM and ECV determined in the adults from centre 1 and then compared with adult data from centre 3. RESULTS: In children, the ratio of eECV to ECV was 1.04 (SD 0.18). In centre 1, eLBM (kg) was 3.81 (SD 0.55) times greater than ECV (litres) in men (n=50) and 3.77 (0.77) times greater in women (n=51). eLBM in children was therefore derived by multiplying eECV by 3.8. In children, eLBM showed a close linear correlation with measured ECV (eLBM=3.50ECV+2.0; R(2)=0.857), similar to adults (eLBM=2.82ECV+14.5; R(2)=0.582). In all groups, eLBM/weight correlated inversely with weight. CONCLUSIONS: In terms of the relationships between eLBM, ECV, and weight, children are similar to adults. Therefore, drug dosage in children should also be based on eLBM rather than weight.

Imaging of multidrug resistance in cancer.

Primary intrinsic and/or acquired multidrug resistance (MDR) is the main obstacle to successful cancer treatment. Functional molecular imaging of MDR in cancer using single photon or positron emitters may be helpful to identify multidrug-resistant tumours and predict not only those patients who are resistant to treatment, with a clinically unfavourable prognosis, but also those who are susceptible to the development of drug toxicity or even certain tumours . Variations in the mdr1 gene product may directly affect the therapeutic effectiveness, and single nucleotide polymorphisms for the mdr1 gene may be associated with altered oral bioavailability of MDR1 substrates, drug resistance, and a susceptibility to some human diseases. The challenge of translating the concept of MDR modulation in vivo involves a complex cellular interplay between both malignant and normal cells. Integration and correlation of functional single photon emission tomography or positron emission tomography imaging findings with mdr1 genotype and clinical data may contribute to efficient management by selecting cancer patients with the appropriate molecular phenotype for maximal individual therapeutic benefit, as well as those who are non-responders. This review describes a role for functional imaging of classical mechanisms of MDR with an emphasis on readily available [(99m)Tc]MIBI scintigraphy. MIBI scintigraphy has been shown to be a non-invasive cost-effective in vivo assay of ATP-binding cassette transporters associated with MDR in cancer, including P-glycoprotein, multidrug-resistant protein 1 and breast cancer resistant protein. New imaging agents for molecular targets such as vascular endothelial growth factor and HER2 receptors, may potentially be combined with MDR imaging substrates to more accurately predict the therapeutic response to anticancer drugs, guiding individualised treatment while minimising the economic health costs of ineffective therapy in an era of personalised medicine.

Cassie-Baxter to Wenzel state wetting transition: scaling of the front velocity.

We experimentally study the dynamics of water in the Cassie-Baxter state to Wenzel state transition on surfaces decorated with assemblies of micrometer-size square pillars arranged on a square lattice. The transition on the micro-patterned superhydrophobic polymer surfaces is followed with a high-speed camera. Detailed analysis of the movement of the liquid during this transition reveals the wetting front velocity dependence on the geometry and material properties. We show that a decrease in gap size as well as an increase in pillar height and intrinsic material hydrophobicity result in a lower front velocity. Scaling arguments based on balancing surface forces and viscous dissipation allow us to derive a relation with which we can rescale all experimentally measured front velocities, obtained for various pattern geometries and materials, on one single curve.

Sympathetic nerve damage as a potential cause of lymphoedema after axillary dissection for breast cancer.

BACKGROUND: The physiological disturbances leading to lymphoedema after breast cancer surgery are poorly understood. Damage to sympathetic nerves during axillary lymph node dissection (ALND), leading to increased capillary fluid filtration, was investigated as a possible contributory factor. METHODS: The integrity of the upper limb sympathetic nervous system was tested in 36 patients before, and 3 and 12 months after ALND. Forearm vascular resistance (FVR), calculated from forearm blood flow and mean systemic arterial pressure, was measured before and after exposure to lower-body negative pressure. Forearm venous compliance was measured using (99m)Tc-labelled autologous erythrocytes and radionuclide plethysmography before and after cold water immersion of the feet. RESULTS: There were clear changes in FVR and venous compliance in response to sympathetic stimulation but no differences attributable to surgery or between the nine patients who developed lymphoedema and the 27 who did not; nor were there differences between the two arms. There was a trend towards lower preoperative FVR in patients who developed lymphoedema. CONCLUSION: Lymphoedema is not the result of sympathetic nerve damage sustained during ALND. Preoperative FVR may help predict who will get lymphoedema following this surgery.

A pilot study of dual-isotope lymphoscintigraphy for breast sentinel node biopsy comparing intradermal and intraparenchymal injection.

AIMS: Identification of sentinel lymph nodes (SLN) may depend on the tissue plane of tracer injection. To explore this, we developed a dual-isotope technique to compare the lymphatic drainage basins accessed by intradermal and parenchymal injections. METHODS: Fifteen breast cancer patients had simultaneous parenchymal and intradermal injections of (99m)Tc-labelled human immunoglobulin G (HIG) and (111)In-HIG, respectively, 2-4h before axillary lymph node clearance surgery. All 228 freshly dissected nodes were assayed by well counting and examined for metastatic disease by haematoxylin/eosin staining and immuno-histochemistry. RESULTS: Total nodal uptake following intradermal injection was 10 times more than after parenchymal injection. Tracer uptake within the first three draining nodes divided patients into three groups; four (group 1) had identical 1st, 2nd and 3rd echelon nodes, six (group 2) had identical 1st and 2nd echelon nodes and five (group 3) had different 1st echelon nodes. With respect to the first, second and third groups, there was close, moderate and poor correlation (Pearson), respectively, between individual nodal counts accumulated from the two injection sites. Of eight patients with nodal disease, the SLN identified by intradermal and parenchymal injections contained disease in seven and four patients, respectively. CONCLUSIONS: Comparison of nodal tracer distributions from the two injection planes allows a functional model to be developed with two possible routes of drainage from the parenchymal plane, one joining the tract from the areolar plexus and the other passing independently to the axilla which builds upon Sappey's original anatomical model. This may explain the variable uptake, discordance and false negative SLN identification.

Obesity does not accelerate the decline in glomerular filtration rate associated with advancing age.

Obesity has been suggested as a risk factor for chronic kidney disease. However, it has also been suggested that the association between obesity and impaired glomerular filtration rate (GFR) arises from the invalid use of body surface area (BSA) for scaling. This study assesses the effect of obesity on GFR by comparing the age-dependent decline in obese (body mass index (BMI) >30 kg/m(2); n=149) and non-obese patients (n=589), aged >30 years, referred for measurement of GFR (Cr-51-EDTA and three blood samples). GFR was scaled to a BSA of 1.73 m(2) (GFR/BSA) and extracellular fluid volume of 13 l (GFR/ECV), both corrected for the one-compartment assumption. When non-obese patients were categorized into 10-year age brackets (from 31 to >70), GFR/BSA and GFR/ECV declined from 92 ml per min per 1.73 m(2) and 95 ml per min per 13 l, respectively, at 31-40 years to 58 and 59 at >70. The declines in obese patients were similar with corresponding values of 88 ml per min per 1.73 m(2) and 97 ml per min per 13 l at 31-40 and 57 and 59 at >70 years. Linear regression analysis of non-categorized data from age 40 years showed rates of decline slightly slower in the obese (0.82 vs 0.95 ml per min per 1.73 m(2) per year and 0.87 vs 1.02 ml per min per 13 l per year). No effect of obesity on renal function was shown. Scaling to BSA did not distort the results.

Disease progression in HIV-1 infected children and adolescents--results of a German-Austrian cohort study.

OBJECTIVE: The Paediatric Working Group AIDS (PAAD) initiated a prospective cohort study in order to investigate disease progression in HIV- infected children and adolescents and the effect of antiretroviral treatment regimes. PATIENTS AND METHODS: Between 1998 and 2003, paediatric centres documented HIV-infected patients under clinical care using a questionnaire for basic data and annual follow up. Main outcome measures were: use of antiretroviral therapy, adverse events, disease progression and change of therapeutic regimes. RESULTS: 174 HIV- infected paediatric patients were followed up in 12 centres in Germany and Austria between 1998 and 2003. Initially 54 (31%) patients had no antiretroviral therapy, 35 (20%) received a two-drug regimen (ART) and 85 patients (49%) a highly active antiretroviral therapy (HAART>or=3 drugs). After an observation period of 5 years, 8 patients (4%) had no therapy, 17 (10%) were on ART and 134 patients on HAART (77%). The number of patients with salvage therapy (>or=4 drugs) increased from 5 (3%) to 15 patients (9%). 72 of 166 treated patients (43%) had no change of their drug regimes, 68 patients (41%) had one change and 26 patients (16%)>or=2 changes. Main reasons for changes were increased viral load (49%), immunologic deterioration (21%) and adverse events (14%). During the follow up period no patient died. According to the CDC classification, disease progression was seen in 48 of 174 patients (28%), of whom 20 had deteriorations of clinical categories (A, B, C) and 28 of immunologic categories. Using Kaplan-Meier curves, the mean time from study onset until change of clinical categories was 61 months for patients on HAART, 26 months for patients on ART and 14 months for patients without ART. CONCLUSION: In paediatric patients with HIV infection, disease progression has declined substantially by introduction of HAART. Superiority of HAART compared with ART was demonstrated. Non-adherence as well as other reasons for treatment failure have to be studied more carefully.