Medical hypotheses
-
Alzheimer's disease (AD) includes etiologically heterogeneous disorders characterized by senile or presenile dementia, extracellular amyloid protein aggregations containing an insoluble amyloid precursor protein derivative, and intracytoplasmic tau protein aggregations. Recent studies also show excess neuronal aneuploidy, programmed cell death (PCD), and mitochondrial dysfunction. The leading AD molecular paradigm, the "amyloid cascade hypothesis", is based on studies of rare autosomal dominant variants and does not specify what initiates the common late-onset, sporadic form. ⋯ In our model, the inherited, gene-determined make-up of an individual's electron transport chain sets basal rates of reactive oxygen species (ROS) production, which determines the pace at which acquired mitochondrial damage accumulates. Oxidative mitochondrial DNA, RNA, lipid, and protein damage amplifies ROS production and triggers three events: (1) a reset response in which cells respond to elevated ROS by generating the beta-sheet protein, beta amyloid, which further perturbs mitochondrial function, (2) a removal response in which compromised cells are purged via PCD mechanisms, and (3) a replace response in which neuronal progenitors unsuccessfully attempt to re-enter the cell cycle, with resultant aneuploidy, tau phosphorylation, and neurofibrillary tangle formation. In addition to defining a role for aging in AD pathogenesis, the mitochondrial cascade hypothesis also allows and accounts for histopathologic overlap between the sporadic, late-onset and autosomal dominant, early onset forms of the disease.
-
Human babesiosis, caused by parasitic protozoa of erythrocytes, has escaped usual associates--lower mammals. Thriving in tick guts, it has spread inland from the coasts of America, adopting mankind as a host. Babesia spp. threaten life quality of unsuspecting humans in quickly expanding territories worldwide, including the state of Pennsylvania, USA. ⋯ Physicians practicing throughout Pennsylvania have identified patients with symptomatic babesiosis, but without governmental surveillance or health registries that require doctors to consider and report babesiosis, these cases have not prompted epidemiological concern. Misunderstandings such as, "Isn't that an obscure tropical disease?" are usual responses when doctors are asked about babesiosis, inadvertently trivializing patients and disease. Mandatory reporting of babesiosis should now be considered a medical necessity.
-
Bone metastasis are a frequent complication of cancer, occurring in up to 70% of patients with advanced breast or prostate cancer. The consequences of bone metastasis are often devastating. Osteolytic metastasis can cause different kinds of skeletal related events including severe pain, pathologic fractures, life-threatening hypercalcemia, spinal cord compression, and other nerve-compression syndromes. ⋯ Local calcium also promotes tumor growth and the production of parathyroid hormone-related peptide which in turn stimulates bone resorption. Vitamin D and calcium supplementation during bisphosphonate administration for the purpose of elimination of the side effects related to hypocalcemia in patients with bone metastasis may increase the bone resorption and decrease the efficacy of bisphosphonates. Therefore, vitamin D and calcium supplementation must not be routinely recommended during bisphosphonate administration.
-
The common physiological rationale for migraine, anger, and epileptic attacks is discussed. The potential importance of homeostatic reactions in brain blood perfusion is described. The author speculates that these attacks are induced to meet some urgent biological needs. ⋯ Migraine attack is a subacute local vasomotor response. In contrast, anger and epileptic attacks are different manifestations of acute solemn general neuropsychiatric vasomotor reflexes. The newer paradigm of the etiological integration of these three kinds of attacks based on cerebral hemodynamic change does not only explain the mechanism of seizure-producing treatments such as electroconvulsive therapy, but also indicates the significance of cerebral vasodilative demands for the particular treatment of migraine, aggressive behavior, and epileptic seizures.