Predicting final infarct size using acute and subacute multiparametric MRI measurements in patients with ischemic stroke

PURPOSE: To identify early MRI characteristics of ischemic stroke that predict final infarct size three months poststroke. MATERIALS AND METHODS: Multiparametric MRI (multispin echo T2-weighted [T2W] imaging, T1-weighted [T1W] imaging, and diffusion-weighted imaging [DWI]) was performed acutely (<24 hours), subacutely (three to five days), and at three months. MRI was processed using maps of apparent diffusion coefficient (ADC), T2, and a self-organizing data analysis (ISODATA) technique. Analyses began with testing for individual MRI parameter effects, followed by multivariable modeling with assessment of predictive ability (R(2)) on final infarct size. RESULTS: A total of 45 patients were studied, 15 of whom were treated with tissue plasminogen activator (tPA) before acute MRI. The acute DWI and DWI-ISODATA mismatch lesion size, and the interactions of ADC, T2, and T2W imaging lesion with tPA remained in the final multivariable model (R(2) = 70%). A large acute DWI lesion or DWI < ISODATA lesion independently predicted increase in the final infract size, with predictive ability 68%. Predictive ability increased (R(2) = 83%) when subacute MRI parameters were included along with acute DWI, DWI-ISODATA mismatch, and acute T2W image lesion size by tPA treatment interaction. Subacute DWI > acute DWI lesion size predicted an increased final infarct size (P < 0.01). CONCLUSION: Acute-phase DWI and DWI-ISODATA mismatch strongly predict the final infarct size. An acute-to-subacute DWI lesion size change further increases the predictive ability of the model.     

Is polydipsia sometimes the cause of oxcarbazepine-induced hyponatremia?

Hyponatremia is a commonly encountered clinical problem with potentially severe complications. Among the underlying implicated etiologies are medications such as oxcarbazepine, which has been well documented and attributed to the syndrome of inappropriate antidiuretic hormones (SIADH). We report the case of a 28-year-old woman with a diagnosis of secondary antiphospholipid syndrome who presented with asymptomatic hyponatremia secondary to excessive water intake after oxcarbazepine ingestion, suggesting a new mechanism for oxcarbazepine-induced hyponatremia.     

Statistical methods for clinical verification of dose-response parameters related to esophageal stricture and AVM obliteration from radiotherapy

The purpose of this work is to provide some statistical methods for evaluating the predictive strength of radiobiological models and the validity of dose-response parameters for tumour control and normal tissue complications. This is accomplished by associating the expected complication rates, which are calculated using different models, with the clinical follow-up records. These methods are applied to 77 patients who received radiation treatment for head and neck cancer and 85 patients who were treated for arteriovenous malformation (AVM). The three-dimensional dose distribution delivered to esophagus and AVM nidus and the clinical follow-up results were available for each patient. Dose-response parameters derived by a maximum likelihood fitting were used as a reference to evaluate their compatibility with the examined treatment methodologies. The impact of the parameter uncertainties on the dose-response curves is demonstrated. The clinical utilization of the radiobiological parameters is illustrated. The radiobiological models (relative seriality and linear Poisson) and the reference parameters are validated to prove their suitability in reproducing the treatment outcome pattern of the patient material studied (through the probability of finding a worse fit, area under the ROC curve and chi2 test). The analysis was carried out for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures are formed, and the total volume of AVM. The estimated confidence intervals of the dose-response curves appear to have a significant supporting role on their clinical implementation and use.     

The effect of Edrecolomab (Mo17-1A) or fluorouracil-based chemotherapy on specific immune parameters in patients with colorectal cancer. A comparative study

OBJECTIVES: We investigated the immune profile of patients with resected Dukes' stage C colorectal cancer (CRC), receiving adjuvant therapy with edrecolomab (Mo17-1A) or first-line 5-fluorouracil (5-FU)-based chemotherapy. PATIENTS AND METHODS: Patients received either 5 doses of Mo17-1A over 13 weeks, or 5-FU/leucovorin, or 5-FU/levamisole over 6 and 12 months, respectively. Peripheral blood was collected postoperatively and 4 months after therapy initiation. Peripheral blood mononuclear cells were tested in the autologous mixed lymphocyte reaction (AMLR), for natural killer (NK) and lymphokine-activated killer (LAK) cell activity. Serum cytokines were quantified by ELISA. RESULTS: Fifty-two patients entered the study. Postoperatively, they exhibited decreased levels of interleukin (IL)-2, interferon-gamma, IL-12, granulocyte-macrophage colony-stimulating factor and IL-15, low cellular immune responses (AMLR, NK- and LAK-cytotoxicity) and increased levels of IL-1beta, tumor necrosis factor-alpha, IL-6, IL-10 and prostaglandin E(2). After four months of therapy, patients receiving edrecolomab demonstrated enhanced AMLR, NK, LAK activity, increased serum levels of cytokines regulating such responses and reduced levels of acute-phase cytokines and immune suppressors, compared to patients treated with conventional chemotherapy. CONCLUSIONS: Postoperative adjuvant therapy with edrecolomab restores the in vivo deficient immune responses of patients with resected Dukes' C CRC despite its clinical ineffectiveness in recent randomized adjuvant trials. These results suggest that further immunological studies with the combination of edrecolomab and chemotherapy are required.     

Peripheral vascular disease in antiphospholipid syndrome

Atherosclerosis has been considered an inflammatory disease based on the finding that atherosclerotic lesion contains activated T lymphocytes reacting with oxidized low-density lipoproteins (oxLDL) and heat shock proteins (HSP); it also contains autoantigens like β₂GPI, a target of antibodies occurring in an immune-mediated thrombophilia called antiphospholipid syndrome (APS). Further support to this hypothesis comes from the cross-reactivity, which occurs between antiphospholipid antibodies (aPL) and antibodies to oxLDL. Animal experiments have shown that aPL are associated with atheroma. In addition, accelerated atherosclerosis has been detected in patients with a prototype systemic autoimmune disease, such as systemic lupus erythematosus (SLE). However, the association of APS or aPL with atherosclerosis is a matter of debate due to the small numbers of patients studied, and the fact that traditional risk factors for atherosclerosis coexist. The prevalence of APS ranges from 1.7% to 6%, and that of aPL reaches to 14% among patients with peripheral vascular disease defined on the basis of clinical outcomes. On the other hand, the prevalence of asymptomatic atherosclerosis, defined in terms of plaques in ultrasonography, reaches to 15% of patients with APS compared to 9% of SLE patients and 3% of normal controls. Among SLE patients with aPL, the prevalence of plaques ranges from 6% in premenopausal women to 31% in unselected patients. Less than 10% of APS patients express premature atherosclerosis in the absence of other risk factors. Which APS patient will develop atherosclerosis is unpredictable.     

Tocol emulsions for drug solubilization and parenteral delivery

Tocols represent a family of tocopherols, tocotrienols, and their derivatives, and are fundamentally derived from the simplest tocopherol, 6-hydroxy-2-methyl-2-phytylchroman, which is referred to as "tocol". The most common tocol is D-alpha-tocopherol, also known as vitamin E. Tocols can be excellent solvents for water insoluble drugs and are compatible with other cosolvents, oils and surfactants. This review highlights the major developments in the use of tocols in parenteral emulsions for drug delivery, with a focus on drug solubilization, physicochemical properties, and biopharmaceutical applications. Tocol emulsions offer an appealing alternative for the parenteral administration of poorly soluble drugs, including major chemotherapeutics such as paclitaxel. Data will be presented on solubilization of paclitaxel, a key chemotherapeutic agent, and its corresponding formulation development, toxicity, efficacy and pharmacokinetic studies in animal models and humans. The breadth of the utility of tocol-based emulsions will be discussed and examples of specific therapeutic drugs and applications will be provided. As these formulations progress further in the clinic, the therapeutic utility of tocol emulsions is anticipated to expand.