Vasopressin receptor subtypes differentially modulate calcium-activated potassium currents in the horizontal limb of the diagonal band of Broca

Because many testicular toxicants cause damage to specific stages of spermatogenesis, the present study has investigated the utility of a model in which the testis is synchronized to contain only a few closely related spermatogenic stages. The susceptibility of different stages to 1,3-dinitrobenzene (1,3-DNB) toxicity was investigated in rats, the testes of which had been stage synchronized by a vitamin A depletion/repletion (VADR) procedure. 1,3-DNB (25 mg/kg, IP) or vehicle was injected 58, 61, or 78 d after vitamin A readministration, and testicular histopathology was evaluated 48 h later. At the time of sacrifice, testes in the three groups were synchronized to stages I-VI, VII-IX, or X-XIV+I. The data indicated that tubules in all stages of spermatogenesis, in both synchronized and unsynchronized animals, demonstrated histopathologic changes in response to 1,3-DNB. However, the lesion seen in synchronized animals was more severe and less stage specific than that seen in weight-matched, unsynchronized animals. This increase in degree of susceptibility could be partially explained by differences in toxicokinetics. Stage-synchronized testes could provide unique insights into stage-specific cellular and molecular events, especially for in vitro studies where the stage enrichment could be maximally exploited. However, results obtained from in vivo toxicity studies using animals subjected to VADR should be interpreted carefully in light of the confounding physiologic/metabolic perturbations potentially induced by the VADR procedure.     

An in vitro model for toxin-mediated vascular leak syndrome: ricin toxin A chain increases the permeability of human endothelial cell monolayers

Vascular leak syndrome (VLS) is the dose-limiting toxicity observed in clinical trials of immunotoxins containing ricin toxin A chain (RTA). RTA itself is thought to cause VLS by damaging vascular endothelial cells, but the exact mechanism remains unclear. This is partially due to the paucity of appropriate models. To study VLS, we developed an in vitro model in which human umbilical vein-derived endothelial cells were first grown to confluence on microporous supports and then cultured under low pressure in the presence or absence of RTA. Endothelial cell barrier function was assessed by measuring the volume of fluid that passed through each monolayer per unit time. We found that RTA significantly increased monolayer permeability at times and concentrations consistent with the onset of VLS in patients treated with RTA-based immunotoxins. Scanning electron microscopy showed that intercellular gaps formed in endothelial monolayers exposed to RTA. Intercellular gap formation followed endothelial cell death caused by the enzymatic activity of RTA. We conclude that RTA is directly toxic to endothelial cells in vitro and speculate that this contributes to VLS in vivo.     

Acquired hemophilia and rheumatoid arthritis. Value of intravenous immunoglobulins

The authors report an exceedingly rare complication of rheumatoid arthritis, i.e. acquired hemophilia due to anti-factor VIII autoantibody production. Treatment with intravenous immune globulin ensured control of hemorrhagic manifestations by inducing a transient rise in factor VIII level.     

The crystal structure of an Fe-superoxide dismutase from the hyperthermophile Aquifex pyrophilus at 1.9 A resolution: structural basis for thermostability

The incidence of stress fractures is increasing among competitive and recreational athletes as well as among children and the elderly. By understanding the continuum of bone's response to stress and maintaining an appropriate index of suspicion, the health care provider can diagnose these injuries appropriately. An accurate history and examination is essential and will differentiate stress fractures from other stress reactions. The more common stress fractures are discussed.     

Family practice physicians' firearm safety counseling beliefs and behaviors

The purpose of this study was to identify family physicians' firearm safety counseling beliefs and behaviors. A survey was mailed to a random sample of 600 members of the American Academy of Family Physicians. A three wave mailing technique was used to maximize the response rate and yielded 271 usable surveys (55% response rate). Outcome measures included training experience in firearm safety counseling, the prevalence of firearm safety counseling by family physicians, and their perceptions regarding such counseling. The majority (78%) of family physicians lacked formal training on how to counsel patients about firearm safety and 49% believed more time should be spent in residency programs on firearm safety counseling. The majority (84%) of respondents never or rarely counseled patients on firearm safety and 50% believed firearm safety counseling should be a low priority in their delivery of primary care. The majority of respondents did not regularly counsel patients about firearm safety, did not believe firearm safety counseling should be a priority, and did not believe firearm safety counseling would be effective in reducing firearm-related trauma.     

Tetraparesis following dental extraction: case report and discussion of preventive measures for cervical spinal hyperextension injury

This concerns a patient with compression myelopathy following passive hyperextension of the cervical spine during a dental procedure. Although he had been asymptomatic prior to the procedure, subsequent cervical spinal imaging revealed advanced spondylosis and spinal stenosis. Spinal stenosis is often asymptomatic for a long time. However, when radiculomyelopathy occurs after minor trauma to the head or neck, the patient is often found to have spinal stenosis. Specifically, hyperextension of a cervical spine with spondylotic changes can lead to compression myelopathy. Acquired spinal stenosis correlates positively with aging. As the size of the elderly population continues to increase the prevalence of cervical spondylotic radiculo-myelopathy will likely increase as well. Since appropriate precautions against potential neurologic damage can be undertaken, we suggest radiographic screening for pre-existing spinal stenosis prior to a procedure requiring hyperextension of the neck. Preventive measures for individuals with asymptomatic spondylotic changes and education of all health-care professionals to avoid abrupt or prolonged hyperextension of the cervical spine is emphasized.