Diffusion-weighted MR imaging in monitoring the effect of a vascular targeting agent on rhabdomyosarcoma in rats

PURPOSE: To evaluate diffusion-weighted magnetic resonance (MR) imaging for monitoring tumor response in rats after administration of combretastatin A4 phosphate. MATERIALS AND METHODS: Study protocol was approved by local ethical committee for animal care and use. Rhabdomyosarcomas implanted subcutaneously in both flanks of 17 rats were evaluated with 1.5-T MR unit by using four-channel wrist coil. Transverse T2-weighted fast spin-echo sequences, T1-weighted spin-echo sequences before and after gadodiamide administration, and transverse echo-planar diffusion-weighted MR examinations were performed before, 1 and 6 hours, and 2 and 9 days after intraperitoneal injection of vascular targeting agent (combretastatin A4 phosphate, 25 mg/kg). Apparent diffusion coefficient (ADC) was automatically calculated from diffusion-weighted MR imaging findings. These findings were compared with histopathologic results at each time point. For statistical analysis, paired Student t tests with Bonferroni correction for multiple testing were used. RESULTS: T1-weighted images before combretastatin administration showed enhancement of solid tumor tissue but not of central necrosis. At 1 and 6 hours after combretastatin injection, enhancement of solid tissue disappeared almost completely, with exception of small peripheral rim. At 2 and 9 days after combretastatin injection, enhancement progressively reappeared in tumor periphery. ADC, however, showed decrease early after combretastatin injection ([1.26 +/- 0.16]x 10(-3) mm2/sec before, [1.18 +/- 0.17]x 10(-3) mm2/sec 1 hour after [P=.0005] and [1.08 +/- 0.14]x 10(-3) mm(2)/sec 6 hours after [P=.0007] combretastatin A4 phosphate injection), histologically corresponding to vessel congestion and vascular shutdown in periphery but no necrosis. An increase of ADC ([1.79 +/- 0.13]x 10(-3) mm2/sec) (P <.0001) 2 days after combretastatin A4 phosphate injection was paralleled by progressive histologic necrosis. A significant (P <.0001) decrease in ADC 9 days after treatment ([1.41 +/- 0.15]x 10(-3) mm2/sec) corresponded to tumor regrowth. CONCLUSION: In addition to basic relaxation-weighted MR imaging and postgadolinium T1-weighted MR imaging to enable prompt detection of vascular shutdown, diffusion-weighted MR imaging was used to discriminate between nonperfused but viable and necrotic tumor tissues for early monitoring of therapeutic effects of vascular targeting agent.     

The relationship between reticulocyte hemoglobin content with C-reactive protein and conventional iron parameters in dialysis patients

Adequate iron stores are a prerequisite for successful erythropoietin (EPO) therapy in hemodialysis (HD) patients. Nevertheless, iron status estimation in HD patients remains problematic, as most parameters are influenced by inflammation. The reticulocyte hemoglobin content (CHr) has recently been proposed as a useful tool in iron status assessment. However, the effect of inflammation on CHr remains unstudied. This study aimed to assess the relationship between CHr with other parameters of iron status as well as with C-reactive protein (CRP). This relationship was studied in all the patients (n=61) at our dialysis unit. CHr was significantly and positively related to transferrin saturation (TS) (rho=0.26; p<0.05) and inversely to the percentage of hypochromic red blood cells (%Hypo) (rho=-0.63; p<0.0001), but not to serum ferritin. CHr was strongly and inversely related to log CRP (rho=-0.50; p<0.0001). Despite the use of maintenance intravenous (i.v.) iron doses and relatively high serum ferritin levels, a large percentage of patients were in a state of functional iron deficiency (%Hypo > or = 6 in 41% of patients and CHr < or = 29 pg in 13% of patients). This percentage was far lower in patients with CRP levels below the detection limit (2 mg/L) (26% and 0%, respectively). In conclusion, CHr is related to both TS and %Hypo, but not to serum ferritin, and is strongly influenced by the presence of inflammation (as determined by CRP). In patients with elevated CRP levels, it is very difficult to reach target iron status levels without exceeding the upper limits for serum ferritin.     

Rising prevalence of HIV-1 non-B subtypes in Belgium: 1983-2001

This study documented the HIV-1 subtype distribution in 2 Belgian hospitals and determined predictive demographics for non-B subtypes. Overall, subtype B was the most prevalent subtype in this population, followed by subtypes A and C. Several recombinants were detected, circulating recombinants as well as new ones. We found a rise in non-B subtypes from 0% in 1983 to 57% in 2001. The Cochran-Armitage trend test (P < 0.001) as well as the correlation analysis (R = 0.71, P = 0.0006) was highly significant. Recombinants were also increasing in this patient population from 0% in 1983 to 10% in 2001, with good support from the statistical analyses (trend test P < 0.001; correlation analysis R = 0.67, P = 0.0016). Heterosexual route of infection, black African race, African origin of the virus, and year of diagnosis were predictors for infection with non-B subtypes in multivariate analysis. This analysis indicates that the prevalence of non-B subtypes and recombinants in this patient population is high and increasing. Gathering demographic and sequence information from newly diagnosed patients could be useful to further follow the spread of non-B subtypes in Belgium and Europe, but subtyping based on sequence information still remains the most reliable method.     

Congenital nasal piriform aperture stenosis or bony inlet stenosis: a report of three cases

BACKGROUND: Congenital nasal piriform aperture stenosis is an uncommon disorder causing nasal obstruction in neonates. Findings on computed tomography (CT) greatly facilitate the diagnosis. METHODS: Three cases of congenital nasal piriform aperture stenosis are reported, with an emphasis on CT findings. CONCLUSIONS: At birth, a diameter of the piriform aperture at the level of the inferior nasal meatus of > or =5 mm on CT may indicate a good chance of success using conservative treatment.     

Subcutaneous nodules with malignant presentation, but caused by infection

Three patients, a woman aged 32, a boy aged 6.5 and a man aged 56 years, presented with a subcutaneous mass suggesting a malignancy: respectively a rubbery swelling, painful to the touch below the left scapula, a partly massive, partly soft swelling on the inside of the left upper leg, and a non-fluctuating mass near the right eighth rib, parasternally. Additional diagnostic investigation revealed an infectious cause: respectively Mycobacterium tuberculosis, Bartonella henselae and Salmonella typhi. Antimicrobial therapy was successful. Subcutaneous masses suspected of being a benign or malignant tumour are sometimes caused by an infection. The differential diagnosis is extensive. Sometimes the travel anamnesis yields helpful information. It is concluded that besides histopathological examination, microbiological investigation can play a major role in the evaluation of subcutaneous masses.     

Non-pharmacological management of type 2 diabetes

Major studies have demonstrated an association between poor glycaemic control and the development of micro - and macrovascular complications in type 2 diabetes. Optimized metabolic control, including treatment of hyperglycaemia and other risk factors, reduces the risk of complications. Current strategies aiming at achieving the best possible control include a non-pharmacological approach consisting of lifestyle intervention using physical exercise and modification of nutrition intakes in the early stage of type 2 diabetes, or in later stages, combined with pharmacotherapy. Such an approach is also efficient in preventing type 2 diabetes in patients with impaired glucose tolerance. The purpose of this review is to analyse, in a clinical practice perspective, the current recommendations with respect to lifestyle modifications.     

Involvement of the sigma 1 receptor in the modulation of dopaminergic transmission by amantadine

Pharmacological effects of amantadine on dopaminergic transmission are proposed to result from an uncompetitive antagonism at glutamate N-methyl-D-aspartate (NMDA) receptors. However, our previous studies examining amantadine-mediated dopamine receptor regulation in the rat striatum revealed a discrepancy from a direct interference with glutamate transmission. Preliminary in vitro binding data from the literature suggested the interaction of amantadine with the sigma1 receptor. Therefore, we have now further characterized the pharmacological properties of amantadine and memantine at this receptor and investigated its involvement in the modulation of striatal dopaminergic transmission. Our binding studies using [3H]-(+)SKF-10,047 indicated that amantadine and memantine behave as ligands of the sigma(1) receptor in rat forebrain homogenates (Ki values of 7.44 +/- 0.82 and 2.60 +/- 0.62 microm, respectively). In NG108-15 neuroblastoma cells, both drugs (amantadine (100 microm) and memantine (10 microm)) potentiated the bradykinin-induced mobilization of intracellular Ca2+, mimicking the effect of the sigma1 receptor agonist PRE-084 (1 microm). Finally, we previously showed that in striatal membranes from amantadine-treated rats, the functional coupling of dopamine receptors with G-proteins was enhanced. Similarly, PRE-084 dose-dependently increased the [35S]GTPgammaS binding induced by dopamine (Emax 28 and 26% of basal, 0.3 and 1 mg/kg PRE-084, respectively). By contrast, BD1047, which is without effect on its own, antagonized the effects of amantadine and PRE-084. Together, these data demonstrate that aminoadamantanes behave as sigma1 receptor agonists, and confirm an involvement of this receptor in modulating dopamine receptors exerted by therapeutically relevant concentrations of amantadine.     

Patient access to the medical file

A new law regulates the access of the patients to their medical files in Belgium. The authors discuss the implications of this law for everyday medical practice.     

Multiplex opsonophagocytosis assay (MOPA): a useful tool for the monitoring of the 7-valent pneumococcal conjugate vaccine

Pneumococcal conjugate vaccination is highly efficacious against invasive diseases in young children. Since host protection is mainly mediated by opsonin-dependent phagocytosis, the in vitro measurement of opsonophagocytic activity of the anti-capsular antibodies is assumed to be a reliable correlate of protection to monitor vaccine efficacy. Unfortunately, the methods used so far are all tedious to perform and material-consuming. Therefore, we modified the multi-specificity opsonophagocytosis killing assay (MSOPKA) into a high-throughput method, which simultaneously measures the opsonophagocytosis against the seven serotypes covered by the current conjugate vaccine in a single assay. In the so-called multiplex opsonophagocytosis assay (MOPA), a mixture containing equal numbers of colony forming units (CFUs) of chloramphenicol-resistant serotype 4, spectinomycin-resistant serotype 6B, streptomycin-resistant serotype 9V, erythromycin-resistant serotype 14, rifampicin-resistant serotype 18C, tetracycline-resistant serotype 19F, and trimethoprim-resistant serotype 23F pneumococci was used as a target mixture and incubated with serial dilutions of test serum. After opsonophagocytosis by differentiated HL-60 cells in the presence of complement, the samples were spotted onto different blood agar plates containing the seven selective antibiotics, respectively. Opsonophagocytosis was calculated as the highest serum dilution resulting in 90% or more reduction in CFUs. The data obtained by this assay correlated well with the data obtained by the MSOPKA. In conclusion, the MOPA simultaneously measures opsonophagocytosis capacity of serum against the capsular serotypes included in the 7-valent pneumococcal conjugate vaccine in a high-throughput fashion, requiring low volumes of patient sera.