Osteonecrosis of the jaw and bisphosphonate treatment for osteoporosis

A potential side effect associated with bisphosphonates, a class of drugs used in the treatment of osteoporosis, Paget's disease and metastatic bone disease, is osteonecrosis of the jaw (ONJ). The incidence of ONJ in the general population is unknown; this rare condition also may occur in patients not receiving bisphosphonates. Case reports have discussed ONJ development in patients with multiple myeloma or metastatic breast cancer receiving bisphosphonates as palliation for bone metastases. These patients are also receiving chemotherapeutic agents that might impair the immune system and affect angiogenesis. The incidence or prevalence of ONJ in patients taking bisphosphonates for osteoporosis seems to be very rare. No causative relationship has been unequivocally demonstrated between ONJ and bisphosphonate therapy. A majority of ONJ occurs after tooth extraction. Furthermore, the underlying risk of developing ONJ may be increased in osteoporotic patients by comorbid diseases. Treatment for ONJ is generally conservative.     

Regional patterns and clinical correlates of basal ganglia morphology in non-medicated schizophrenia

Although structural changes of the basal ganglia are widely implicated in schizophrenia, prior findings in chronically medicated patients show that these changes relate to particular antipsychotic treatments. In unmedicated schizophrenia, local alterations in morphological parameters and their relationships with clinical measures remain unknown. Novel surface-based anatomical modelling methods were applied to magnetic resonance imaging data to examine regional changes in the shape and volume of the caudate, the putamen and the nucleus accumbens in 21 patients (19 males/2 females; mean age=30.7+/-7.3) who were either antipsychotic-na?ve or antipsychotic-free for at least 1 year and 21 healthy comparison subjects (19 males/2 females; mean age=31.1+/-8.2). Clinical relationships of striatal morphology were based on exploratory analyses. Left and right global putamen volumes were significantly smaller in patients than controls; no significant global volume effects were observed for the caudate and the nucleus accumbens. However, surface deformation mapping results showed localized volume changes prominent bilaterally in medial/lateral anterior regions of the caudate, as well as in anterior and midposterior regions of the putamen, pronounced on the medial surface. A significant positive correlation was observed between right anterior putamen surface contractions and affective flattening, a core negative symptom of schizophrenia. The diagnostic effects of local surface deformations mostly pronounced in the associative striatum, as well as the correlation between anterior putamen morphology and affective flattening in unmedicated schizophrenia suggest disease-specific neuroanatomical abnormalities and distinct cortical-striatal dysconnectivity patterns relevant to altered executive control, motor planning, along with abnormalities of emotional processing.     

Computer-assisted colonoscopy (the NeoGuide Endoscopy System): results of the first human clinical trial ("PACE study")

OBJECTIVES: Unsedated colonoscopy is an uncomfortable procedure for most patients. Discomfort during colonoscopy is largely related to looping of the colonoscope, which displaces the colon from its native configuration and stretches attachments to the mesentery. A novel computer-assisted colonoscope utilizes a fully articulated, computer-controlled insertion tube. On manual insertion of the colonoscope, the position and angle of the scope's tip are encoded into a computer algorithm. As the colonoscope is advanced, the computer directs each successive segment to take the same shape that the tip had at a given insertion depth. The insertion tube thus changes its shape at different insertion depths in a "follow-the-leader" manner. METHODS: This initial clinical trial with this novel colonoscopy system was designed as a prospective, nonrandomized, unblinded, feasibility study. Three physicians of varying levels of experience participated in the study. RESULTS: Eleven consecutive patients (seven men, four women, age range 19-80) meeting inclusion criteria for screening or diagnostic colonoscopy were enrolled in the study. The cecum was reached in 10 consecutive patients (100%). Findings included diverticular disease in two cases and multiple colonic polyps in two cases. Postprocedure assessment at discharge, 48 h, and 30 days revealed no complications or adverse effects. Physician satisfaction and patient acceptance of this new technique were high. CONCLUSIONS: In this limited, first of its kind feasibility study, the computer-assisted colonoscope was shown to perform colonoscopy safely and effectively. The colonoscope's unique design limited loop formation during colonoscopy. Large-scale clinical trials are indicated.     

Coronary-subclavian steal: presentation and management: two case reports

Subclavian stenosis is a highly prevalent and underrecognized clinical entity. In patients with a history of coronary artery bypass grafting utilizing a left internal mammary artery, subclavian artery stenosis can cause coronary-subclavian steal, leading to myocardial ischemia. Traditionally, this has been treated surgically with a vascular bypass operation. Two cases of coronary-subclavian steal syndrome are presented, 1 treated percutaneously with angioplasty and stent, and 1 treated with a combined endovascular-surgical procedure.     

Natural killer cell-derived human granzyme H induces an alternative, caspase-independent cell-death program

Granzyme H (GzmH) belongs to a family of 5 human serine proteases that are expressed by cytotoxic immune effector cells. Although GzmH is most closely related to the caspase-activating granzyme B (GzmB), neither a natural substrate nor a role in immune defense reactions has been demonstrated for this orphan granzyme. In rodents, multiple related genes exist, but none of these can be regarded as functional homologs. Here we show that host cells are efficiently killed by GzmH after perforin and streptolysin O-mediated delivery into the cytosol. Dying cells show typical hallmarks of programmed cell death, such as mitochondrial depolarization, reactive oxygen species (ROS) generation, DNA degradation, and chromatin condensation. Contrary to GzmB, cell death by GzmH does not involve the activation of executioner caspases, the cleavage of Bid or inhibitor of caspase-activated DNase (ICAD), or the release of cytochrome c. The high expression levels of GzmH in naive natural killer (NK) cells and its potent killing ability strongly support the role of the protease in triggering an alternative cell-death pathway in innate immunity.