99 research outputs found
IL-33 reflects dynamics of disease activity in patients with autoimmune hemolytic anemia by regulating autoantibody production
A Phase I study of the angiogenesis inhibitor SU5416 (semaxanib) in solid tumours, incorporating dynamic contrast MR pharmacodynamic end points
SU5416 (Z-3-[(2,4-dimethylpyrrol-5-yl)methylidenyl]-2-indolinone; semaxanib) is a small molecule inhibitor of the vascular endothelial growth factor receptor (VEGFR)2. A Phase I dose escalation study was performed. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used as a pharmacodynamic assessment tool. In all, 27 patients were recruited. SU5416 was administered twice weekly by fixed rate intravenous infusion. Patients were treated in sequential cohorts of three patients at 48, 65, 85 110 and 145âmgâmâ2. A further dose level of 190âmgâmâ2 after a 2-week lead in period at a lower dose was completed; thereafter, the cohort at 145âmgâmâ2 was expanded. SU5416 showed linear pharmacokinetics to 145âmgâmâ2 with a large volume of distribution and rapid clearance. A significant degree of interpatient variability was seen. SU5416 was well tolerated, by definition a maximum-tolerated dose was not defined. No reproducible changes were seen in DCE-MRI end points. Serial assessments of VEGF in a cohort of patients treated at 145âmgâmâ2 did not show a statistically significant treatment-related change. Parallel assessments of the impact of SU5416 on coagulation profiles in six patients showed a transient effect within the fibrinolytic pathway. Clinical experience showed that patients who had breaks of therapy longer than a week could not have treatment reinitiated at a dose of 190âmgâmâ2 without unacceptable toxicity. The 145âmgâmâ2 dose level is thus the recommended dose for future study
Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts
Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007).
Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of âtotal Alâassumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold.
The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2âąâ, generate Al superoxides [Al(O2âą)](H2O5)]+ 2. Semireduced AlO2âą radicals deplete mitochondrial Fe and promote generation of H2O2, O2 âą â and OHâą. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates.
Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants.
The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances
The heat shock response in neurons and astroglia and its role in neurodegenerative diseases
An outbreak of dengue fever in Peri Urban slums of Chandigarh, India, with special reference to entomological and climatic factors
Primary pulmonary malignant teratoma with yolk sac element associated with hematologic neoplasia
We describe the unique case of a primary pulmonary malignant teratoma with yolk sac elements, associated with hematologic neoplasia. This 20-year-old male was admitted with complaints of fever, right-sided chest pain, dry cough, and hemoptysis. Necropsy revealed a mass in the right middle and upper lobe which microscopically was a malignant teratoma with yolk sac element. The associated hematologic neoplasia was a myelofibrosis, cellular phase, with myeloid metaplasia in liver, spleen, hilar lymph nodes, left adrenal gland, and lower lobe of the right lung
Case Report - Mucoepidermoid Carcinoma of the Bronchus: Is Conservative Surgery Always Justified?
A case of mucoepidermoid carcinoma of the bronchus in a 7-year-old boy
is reported. The patient underwent right pneumonectomy. Histologically,
the tumor was a low-grade muco-epidermoid carcinoma arising from the
bronchus with lymph node metastasis in the drainage area. Presence of
lymph node metastasis in this low-grade tumor suggests the possibility
of early progression of disease in what has until now been considered a
very slow growing tumor. Aggressive surgery may be necessary in these
situations
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