Unveiling the HER2-low phenomenon: exploring immunohistochemistry and gene expression to characterise HR-positive HER2-negative early breast cancer.

PURPOSE: HER2-low breast cancer (BC) is a novel entity with relevant therapeutic implications, especially in hormone receptor (HR) positive BC. This study examines whether HER2 mRNA through the 21-gene assay, Oncotype DX (ODX), can refine the diagnosis of HER2-low and HER2-zero, obtained by immunohistochemistry (IHC). METHODS: Between Jan 2021 and Jan 2023, 229 consecutive HR-positive HER2-negative early BC (T1-3 N0-1) have been characterised by IHC and ODX. HER2 status by IHC was either zero (IHC-0) or low (IHC-1 + and IHC-2 + /ISH-negative) while HER2-zero was further divided into HER2-null (IHC-0) and HER2-ultralow (IHC-1-10%). HER2 gene expression by ODX was negative if lower 10.7. RESULTS: The distribution of HER2 IHC was as follows: 53.3% HER2-0, 29.25% HER2-1 + , and 17.5% HER2-2 + . The clinicopathological characteristics were similar in the three groups, with higher PgR-negative rate in HER2-zero (13.9% vs 3% vs 5%). The distribution of RS was homogeneous in the three groups with the median HER2 gene expression of 9.20 [IQR: 8.70-9.60]. HER2 gene expression gradually increased as the IHC score, with substantial overlap. After adjusting for confounders, HER2-1 + and HER2 2 + had a significant positive correlation between HER2 gene expression and IHC [OR 1.42, 95% CI 1.21 to 1.68, p < 0.001; OR 1.96, 95% CI 1.61 to 2.37, p < 0.001] compared to the HER2-zero group. HER2 gene expression did not differ between HER2-null and HER2-ultralow subgroups. CONCLUSION: Due to the substantial overlap, the HER2 gene expression is unable to properly distinguish HER2-low and HER2-zero IHC whose accurate identification is critical in the context of HER2-negative BC.

Prognostic value of HER2-low status in breast cancer: a systematic review and meta-analysis.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-low expression in breast cancer has been recently identified as a new therapeutic target. However, it is unclear if HER2-low status has an independent impact on prognosis. MATERIALS AND METHODS: A systematic literature research was carried out to identify studies comparing survival outcomes of patients affected by HER2-low versus HER2-zero breast cancer. Using random-effects models, pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for progression-free survival (PFS) and overall survival (OS) in the metastatic setting as well as disease-free survival (DFS), OS and pathological complete response (pCR) in the early setting. Subgroup analyses by hormone receptor (HoR) status were carried out. The study protocol is registered on PROSPERO (n.CRD42023390777). RESULTS: Among 1916 identified records, 42 studies including 1 797 175 patients were eligible. In the early setting, HER2-low status was associated with significant improved DFS (HR 0.86, 95% CI 0.79-0.92, P < 0.001) and OS (HR 0.90, 95% CI 0.85-0.95, P < 0.001) when compared to HER2-zero status. Improved OS was observed for both HoR-positive and HoR-negative HER2-low populations, while DFS improvement was observed only in the HoR-positive subgroup. HER2-low status was significantly associated with a lower rate of pCR as compared to HER2-zero status both in the overall population (OR 0.74, 95% CI 0.62-0.88, P = 0.001) and in the HoR-positive subgroup (OR 0.77, 95% CI 0.65-0.90, P = 0.001). In the metastatic setting, patients with HER2-low breast cancers showed better OS when compared with those with HER2-zero tumours in the overall population (HR 0.94, 95% CI 0.89-0.98, P = 0.008), regardless of HoR status. No significant PFS differences were found. CONCLUSIONS: Compared with HER2-zero status, HER2-low status appears to be associated with a slightly increased OS both in the advanced and early settings, regardless of HoR expression. In the early setting, HER2-low tumours seem to be associated to lower pCR rates, especially if HoR-positive.

Lateralized deficits after unilateral AAV-vector based overexpression of alpha-synuclein in the midbrain of rats on drug-free behavioral tests.

BACKGROUND: Preclinical rodent models of Parkinson's aim to recapitulate some of the hallmarks of the disease as it presents in humans, including the progressive neuronal loss of dopaminergic neurons in the midbrain as well as the development of a behavioral phenotype. AAV vector-based models of alpha-synuclein overexpression are a promising tool to achieve such animal models with high face and predictive validity. OBJECTIVE: We have developed a preclinical rodent model of Parkinson's disease using an AAV-vector based overexpression of human alpha-synuclein. In the present work we characterize this model on a behavioral and histopathological level. METHODS: We use a AAV9 vector for transgene delivery to overexpress human alpha-synuclein under a CBA promoter. We compare the behavioral and histopathological changes to a AAV vector control group where the transgene was omitted and to that of a 6-OHDA lesion control. We assessed the behavioral performance of these three groups on a series of tests (Cylinder, Stepping, Corridor) at baseline and up to 22 weeks post-injection at which point we performed electrochemical recordings of dopamine kinetics. RESULTS: The overexpression of human alpha-synuclein led to the progressive manifestation of behavioral deficits on all three behavioral tests. This was accompanied with impaired dopamine release and reuptake kinetics as demonstrated by electrochemical detection methods. Histopathological quantifications corroborated the findings that we induced a moderate cell loss with remaining cells displaying pathological markers which are abundant in the brains of human PD patients. CONCLUSIONS: In the present work we developed a characterized a rat model of PD that closely mimics human disease development and pathology. Such model will be of great use for investigation of disease mechanisms and early therapeutic interventions.

When you can't see the wood for the trees. Mucor circinelloides: A rare case of primary cutaneous zygomycosis.

A patient with refractory diffuse lymphoma treated for pulmonary invasive aspergillosis developed a concomitant primary cutaneous mucormycosis. The mucormycete was identified by sequencing as Mucor circinelloides. This case confirms the importance of a rapid pathogen diagnosis in immunocompromised patients and the usefulness of molecular methods for identification of rare fungal species.

Beneficial effects of selective HDL-raising gene transfer on survival, cardiac remodelling and cardiac function after myocardial infarction in mice.

Post-myocardial infarction (MI) ejection fraction is decreased in patients with low high-density lipoprotein (HDL) cholesterol levels, independent of the degree of coronary atherosclerosis. The objective of this study is to evaluate whether selective HDL-raising gene transfer exerts cardioprotective effects post MI. Gene transfer in C57BL/6 low-density lipoprotein receptor (LDLr)(-/-) mice was performed with the E1E3E4-deleted adenoviral vector AdA-I, inducing hepatocyte-specific expression of human apo A-I, or with the control vector Adnull. A ligation of the left anterior descending coronary artery was performed 2 weeks after transfer or saline injection. HDL cholesterol levels were persistently 1.5-times (P<0.0001) higher in AdA-I mice compared with controls. Survival was increased (P<0.01) in AdA-I MI mice compared with control MI mice during the 28-day follow-up period (hazard ratio for mortality 0.42; 95% confidence interval 0.24-0.76). Longitudinal morphometric analysis demonstrated attenuated infarct expansion and inhibition of left ventricular (LV) dilatation in AdA-I MI mice compared with controls. AdA-I transfer exerted immunomodulatory effects and increased neovascularisation in the infarct zone. Increased HDL after AdA-I transfer significantly improved systolic and diastolic cardiac function post MI, and led to a preservation of peripheral blood pressure. In conclusion, selective HDL-raising gene transfer may impede the development of heart failure.

Therapeutic drug monitoring of posaconazole in patients with acute myeloid leukemia or myelodysplastic syndrome.

Posaconazole is a broad-spectrum triazole antifungal available as an oral suspension. Pharmacokinetic data showed a high variability of plasma posaconazole concentrations (PPCs) in patients, suggesting a potential interest in drug monitoring. The aim of our prospective study was to measure the PPCs in prophylactically treated patients to evaluate the impact of different factors on these concentrations. In 40 patients treated prophylactically with posaconazole for acute myeloid leukemia or myelodysplastic syndrome between February 2009 and August 2010, PPCs were measured at day 7 of treatment and then twice weekly. Demographic data, clinical data (including gastrointestinal disorders, comedications, and treatment compliance), caloric and fat intake, and biological data were collected and evaluated. We obtained 275 measurements of PPCs, with a median of 430 ng/ml. PPCs were significantly lower in patients with mucositis (P < 0.001), nausea (P = 0.03), diarrhea (P = 0.03), or vomiting (P = 0.05). PPCs were higher in patients with a higher caloric intake (P = 0.02), while the proportion of fat intake had no influence on PPCs (P = 0.84). The concomitant use of proton pump inhibitors decreased the PPCs (P = 0.02), while the use of tacrolimus increased the PPC (P = 0.03). In the multivariate analysis, the factors influencing the PPCs independently were the concomitant use of tacrolimus (P < 0.001), the presence of mucositis (P = 0.01), and food intake (P = 0.02). Our study confirmed the high variability of posaconazole bioavailability and showed the significant influence of gastrointestinal disorders, food intake, and concomitant medication on the PPCs. However, the optimal PPCs still remain to be defined and correlated with clinical efficacy.

Probable hypersensitivity reaction to vancomycin associating rash, fever and neutropenia.

We describe the case of a 54-year old woman with breast cancer who was treated by vancomycin for febrile neutropenia due to a methicillin-resistant Staphyloccocus epidermidis infection of a surgically implanted catheter. She developed an hypersensitivity reaction to vancomycin associating neutropenia, fever, skin rash and elevated liver enzymes following re-challenge with vancomycin after having been misdiagnosed with septic thrombophlebitis. Following this re-challenge, neutrophils count fell dramatically but promptly resolved after cessation of vancomycin.

Low-density lipoprotein receptor gene transfer in hypercholesterolemic mice improves cardiac function after myocardial infarction.

Left ventricular (LV) function post-myocardial infarction (MI) is adversely influenced by hypercholesterolemia independent of the severity of coronary atherosclerosis. The objective of this study was to evaluate whether lipid lowering by adenoviral low-density lipoprotein (LDL) receptor (AdLDLr) gene transfer in C57BL/6 LDL receptor (LDLr)-deficient mice beneficially affects ventricular remodeling and cardiac function post-MI independent of effects on the coronary circulation. AdLDLr transfer reduced plasma cholesterol by 77% (P<0.0001). Survival 28 days post-MI was higher in AdLDLr-treated mice (95%) compared with control mice (80%) (P<0.05) (hazard ratio for mortality 0.26, 95% confidence interval 0.11-0.84). Infarct size was not significantly different at day 1 and day 7 but was reduced by 18% (P<0.05) at day 28 in AdLDLr MI mice compared with control MI mice. Cardiomyocyte hypertrophy and interstitial fibrosis were reduced and neovascularization was increased in AdLDLr MI mice. LDLr gene transfer had beneficial effects on endothelial progenitor cell (EPC) number and ex vivo EPC function. LV contractility and relaxation were better preserved in AdLDLr MI mice compared with control MI mice. In conclusion, lipid lowering in hypercholesterolemic mice exerts direct cardioprotective effects resulting in enhanced survival, reduced infarct size, decreased ventricular remodeling and better cardiac function.

The impact of antigen expression in antigen-presenting cells on humoral immune responses against the transgene product.

Treatment of genetic diseases by gene therapy is hampered by immune responses against the transgene product. Promoter choice has been shown to be an important parameter of the presence or absence of antibodies against the transgene product after gene transfer. Here, the generality of some of these observations was tested by comparing different murine strains and different transgene products. We show immunological unresponsiveness for human apolipoprotein (apo) A-I in six murine strains after transfer with E1E3E4-deleted adenoviral vectors containing hepatocyte-specific expression cassettes. However, differences in the induction of a humoral immune response against human apo A-I after gene transfer with vectors driven by the major histocompatibility complex class II Ebeta promoter and the ubiquitously active cytomegalovirus promoter were not consistent in these six murine strains. Furthermore, use of a potent hepatocyte-specific expression cassette did not prevent a humoral immune response against human plasminogen in C57BL/6 mice. In contrast, human microplasminogen transfer resulted in stable expression in the absence of an immune response against the transgene product. Taken together, the molecular design of strategies to abrogate or induce an immune response against the transgene product may be hampered by the multitude of parameters affecting the outcome, thus limiting the external validity of results.

Apolipoprotein A-I and lecithin:cholesterol acyltransferase transfer induce cholesterol unloading in complex atherosclerotic lesions.

Plasma levels of high-density lipoprotein (HDL) cholesterol and its major apolipoprotein (apo), apo A-I, are inversely correlated with the incidence of ischemic cardiovascular diseases. Reverse cholesterol transport is likely the main mechanism underlying the atheroprotective effects of HDL. Here, we investigated whether increased HDL cholesterol following hepatocyte-directed adenoviral rabbit apo A-I (AdrA-I) or rabbit lecithin-cholesterol acyltransferase (LCAT) (AdrLCAT) transfer may induce cholesterol unloading in complex atherosclerotic lesions in heterozygous low-density lipoprotein receptor-deficient rabbits fed a 0.15% cholesterol diet for 420 days before and for 120 days after transfer. HDL cholesterol levels increased 2.0-fold (P<0.001) and 1.9-fold (P<0.001) in the 120 days after transfer with AdrA-I and AdrLCAT, respectively, compared to levels just before transfer whereas non-HDL cholesterol remained unchanged. Increased HDL cholesterol following AdrA-I and AdrLCAT transfer resulted in a 31% (P<0.05) reduction of the intima/media ratio in comparison with the control progression group. Compared to the baseline group killed after 420 days of cholesterol diet, AdrA-I and AdrLCAT transfer reduced the percentage of Oil Red O area 1.6-fold (P<0.001) and 1.4-fold (P<0.001), respectively. In conclusion, increased HDL cholesterol after AdrA-I and AdrLCAT transfer inhibits progression of atherosclerosis and induces cholesterol unloading in complex lesions in rabbits.

[Disseminated tuberculosis with severe multi- organ failure in a patient with AIDS]. / Tuberculose disséminée avec défaillance multiviscérale foudroyante au cours d'un sida.

INTRODUCTION: Tuberculosis is the most common infectious complication in HIV infected patients. The incidence of tuberculosis and the proportion of disseminated disease increase with more severe immuno-suppression. Septic shock and multiple organ failure are uncommon but are of markedly bad prognostic significance. CASE REPORT: A forty-four year old HIV seropositive man was admitted to the intensive care unit (ICU) with acute respiratory distress. The patient had been febrile for the previous two weeks. His thoracic radiograph showed a discrete interstitial infiltrate and at bronchoscopy small whitish granulations were observed in the main bronchi. All bacteriological investigations remained negative at the time of ICU admission. The patient died sixteen hours later due to multiple organ failure. Mycobacteria were identified after patient's death on the smear from BAL, from blood cultures, and in a postmortem liver biopsy. CONCLUSIONS: Septic shock is an infrequent complication of disseminated tuberculosis. Mortality is very high. Treatment should be started early in cases with a high diagnostic suspicion.

The size of endothelial fenestrae in human liver sinusoids: implications for hepatocyte-directed gene transfer.

Fenestrae allow the passage of gene transfer vectors from the sinusoidal lumen to the surface of hepatocytes. We have previously shown that the diameter of fenestrae correlates with species and strain differences of transgene expression following intravenous adenoviral transfer. In the current study, we demonstrate that the diameter of fenestrae in humans without liver pathology is 107+/-1.5 nm. This is similar to the previously reported diameter in New Zealand White (NZW) rabbits (103+/-1.3 nm) and is significantly smaller than in C57BL/6 mice (141+/-5.4 nm) and Sprague-Dawley rats (161+/-2.7 nm). We show that the diameter of fenestrae in one male NZW rabbit and its offspring characterized by a more than 50-fold increase of transgene expression after adenoviral gene transfer is significantly (113+/-1.5 nm; P<0.001) larger than in control NZW rabbits. In vitro filtration experiments using polycarbonate filters with increasing pore sizes demonstrate that a relatively small increment of the diameter of pores potently enhances passage of adenoviral vectors, consistent with in vivo data. In conclusion, the small diameter of fenestrae in humans is likely to be a major obstacle for hepatocyte transduction by adenoviral vectors.

Direct comparison of hepatocyte-specific expression cassettes following adenoviral and nonviral hydrodynamic gene transfer.

Hepatocytes are a key target for treatment of inborn errors of metabolism, dyslipidemia and coagulation disorders. The development of potent expression cassettes is a critical target to improve the therapeutic index of gene transfer vectors. Here we evaluated 22 hepatocyte-specific expression cassettes containing a human apo A-I transgene following hydrodynamic transfer of plasmids or adenoviral transfer with E1E3E4-deleted vectors in C57BL/6 mice. The DC172 promoter consisting of a 890 bp human alpha(1)-antitrypsin promoter and two copies of the 160 bp alpha(1)-microglobulin enhancer results in superior expression levels compared to constructs containing the 1.5 kb human alpha(1)-antitrypsin promoter, the 790 bp synthetic liver-specific promoter or the DC190 promoter containing a 520 bp human albumin promoter and two copies of the 99 bp prothrombin enhancer. The most potent expression cassette consists of the DC172 promoter upstream of the transgene and two copies of the hepatic control region-1. Minicircles containing this expression cassette induce persistent physiological human apo A-I or human factor IX levels after hydrodynamic transfer. In conclusion, in this comparative study of 22 hepatocyte-specific expression cassettes, the DC172 promoter in combination with two copies of the hepatic control region-1 induces the highest expression levels following hydrodynamic and adenoviral transfer.

Clostridium difficile colitis in cystic fibrosis patients with and without lung transplantation.

BACKGROUND: Despite a large carriage rate of Clostridium difficile among cystic fibrosis (CF) patients, C. difficile-associated disease (CDAD) is rather rare. In case of lung transplantation, the incidence and clinical aspects of CDAD in this patient population are not well known. METHODS: We reviewed the medical files of all CF patients who presented with symptomatic C. difficile infection from January 1998 to December 2004 and compared the incidence, clinical aspects, severity of disease, and clinical outcome between non-transplanted and transplanted CF patients. RESULTS: Between 1998 and 2004, 106 adult CF patients were followed at our clinic. Forty-nine patients underwent lung transplantation; 15 before 1998 and 34 after 1998. The incidence density of CDAD was higher in transplanted CF patients as compared with non-transplanted CF patients (24.2 vs. 9.5 episodes/100,000 patient-days; risk ratio: 2.93 [1.41-6.08]; P=0.0044). Diarrhea was a very frequent feature, but was notably absent in 20% of the cases. Rates of moderate and severe colitis were similar in both groups. However, only transplanted patients developed complicated colitis. CT scan and endoscopy were performed more frequently in the transplant group. Two transplant recipients died because of CDAD. CONCLUSION: CF patients who undergo lung transplantation are at a higher risk of developing CDAD and seem to present more often atypical and/or complicated disease. CDAD should be part of the differential diagnosis in case of digestive symptoms, even in the absence of diarrhea, and requires early treatment.

Pseudomonas aeruginosa: resistance and therapeutic options at the turn of the new millennium.

Pseudomonas aeruginosa is a major cause of nosocomial infections. This organism shows a remarkable capacity to resist antibiotics, either intrinsically (because of constitutive expression of beta-lactamases and efflux pumps, combined with low permeability of the outer-membrane) or following acquisition of resistance genes (e.g., genes for beta-lactamases, or enzymes inactivating aminoglycosides or modifying their target), over-expression of efflux pumps, decreased expression of porins, or mutations in quinolone targets. Worryingly, these mechanisms are often present simultaneously, thereby conferring multiresistant phenotypes. Susceptibility testing is therefore crucial in clinical practice. Empirical treatment usually involves combination therapy, selected on the basis of known local epidemiology (usually a beta-lactam plus an aminoglycoside or a fluoroquinolone). However, therapy should be simplified as soon as possible, based on susceptibility data and the patient's clinical evolution. Alternative drugs (e.g., colistin) have proven useful against multiresistant strains, but innovative therapeutic options for the future remain scarce, while attempts to develop vaccines have been unsuccessful to date. Among broad-spectrum antibiotics in development, ceftobiprole, sitafloxacin and doripenem show interesting in-vitro activity, although the first two molecules have been evaluated in clinics only against Gram-positive organisms. Doripenem has received a fast track designation from the US Food and Drug Administration for the treatment of nosocomial pneumonia. Pump inhibitors are undergoing phase I trials in cystic fibrosis patients. Therefore, selecting appropriate antibiotics and optimising their use on the basis of pharmacodynamic concepts currently remains the best way of coping with pseudomonal infections.

Species differences in transgene DNA uptake in hepatocytes after adenoviral transfer correlate with the size of endothelial fenestrae.

Sinusoidal fenestrae may restrict the transport of gene transfer vectors according to their size. Using Vitrobot technology and cryo-electron microscopy, we show that the diameter of human adenoviral serotype 5 vectors is 93 nm with protruding fibers of 30 nm. Thus, a diameter of fenestrae of 150 nm or more is likely to be sufficient for passage of vectors from the sinusoidal lumen to the space of Disse and subsequent uptake of vectors in hepatocytes. The average diameter of fenestrae in New Zealand White rabbits (103+/-1.3 nm) was 1.4-fold (P<0.0001) lower than in C57BL/6 mice (141+/-5.4 nm). The percentage of sinusoidal fenestrae with a diameter larger than 150 nm was 10-fold (P<0.01) lower in rabbits (3.2+/-0.24%) than in C57BL/6 mice (32+/-5%), and this resulted in 8.8-fold (P=0.01) lower transgene DNA levels in hepatocytes in rabbits after adenoviral transfer. Injection of N-acetylcysteine combined with transient liver ischemia preceding intraportal transfer in rabbits increased the percentage of sinusoidal fenestrae above 150 nm 2.0-fold (P<0.001) and increased transgene DNA levels in hepatocytes 6.6-fold (P<0.05). In conclusion, species differences in transgene DNA uptake in hepatocytes after adenoviral transfer correlate with the diameter of fenestrae.

Intensive lifestyle changes may affect the progression of prostate cancer.

PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.

[Abnormalities in tattooed skin: sometimes sarcoidosis]. / Afwijkingen in getatoeëerde huid: soms sarcoïdose.

A 43-year-old man presented with a nodular tattoo lesion on his right upperarm. Histologically it resembled the granulomatous reaction seen in systemic sarcoidosis. Further evaluation revealed asymmetrical hilar lymphadenopathy with no interstitial lung disease. Since the patient was a heavy smoker, bronchus carcinoma could not be excluded and cervical mediastinoscopy was performed in order to obtain a lymph-node biopsy. This confirmed the diagnosis of systemic sarcoidosis. The patient was treated by local application of corticosteroids, but with little result. Skin lesions in scars or tattoos may be the first symptom of systemic sarcoidosis. Skin biopsy for histological confirmation of the diagnosis is recommended, as is further investigation to evaluate other organ systems which may be affected.

Optimised tracer-dependent dosage cards to obtain weight-independent effective doses.

PURPOSE: The aim of this study was twofold: firstly, to determine whether the European Association of Nuclear Medicine (EANM) dosage card results in weight-independent effective doses or weight-independent count rates; secondly, to determine whether one dosage card is sufficient for 95 different radiopharmaceuticals, and, if not, how many cards we reasonably need to take into account inter-tracer variability. METHODS: Normalisation factors for count rate and effective dose were calculated as a function of body weight, with 70 kg as standard. Calculations were performed, using whole-body absorption fractions and MIRDOSE 3 software, for seven anthropomorphic phantoms and ten radionuclides. An analytic function for both relations was proposed. Normalisation factors for effective dose for 95 radiopharmaceuticals were investigated using cluster analysis. RESULTS: Normalisation factors for count rate and effective dose can be estimated accurately as a function of body weight W by (W/70)a holding only one parameter, called the a value. The a values for 95 radiopharmaceuticals were classified into three clusters (nA=7, nB=76, nC=12). Cluster A contains tracers for renal studies. Cluster B contains all remaining tracers, except iodine-labelled tracers for thyroid studies and 89Sr for therapy, which belong to cluster C. CONCLUSION: Correction factors proposed by the EANM task group mainly correct for effective dose. They are very similar to the factors obtained for cluster A. Using the EANM factors for tracers belonging to clusters B and C results in significantly higher effective doses to children. We suggest using three tracer-dependent dosage cards for which the correction factors have been calculated to obtain weight-independent effective doses.