Citations

Tremendous attention and energy have been put toward development of minimally invasive techniques in urology to decrease the morbidity of surgery without compromising outcomes. Urologists have remained on the cutting edge of technology, performing procedures via laparoscopic, robotic, and transurethral approaches in procedures that were formerly only performed with an open approach. As the treatment paradigm shifts toward less invasive procedures, the concept of performing surgery through natural body openings has been recognized. Natural orifice translumenal endoscopic surgery (NOTES) eliminates the need for abdominal incisions, theoretically resulting in decreased pain, faster convalescence, improved cosmesis, and absence of wound infections and hernias. While transvesical NOTES has the potential to develop into a viable technology in the clinical setting, it is still in its infancy. Initial studies have demonstrated the feasibility of transvesical NOTES; however, further work must be dedicated to this subject before its routine application in humans. The purpose of this review is to detail the experimental, cadaveric, and clinical work that has been accomplished with transvesical NOTES, in addition to discussing the advantages and disadvantages, technical obstacles, and potential risks that accompany the use of the bladder as a portal for surgery.

ABSTRACTPasteurella (Mannheimia) haemolyticaleukotoxin (Lkt) causes cell type- and species-specific effects in ruminant leukocytes. Recent studies indicate thatP. haemolyticaLkt binds to bovine CD18, the common subunit of all β2 integrins. We designed experiments with the following objectives: to identify which member of the β2 integrins is a receptor for Lkt; to determine whether Lkt binding to the receptor is target cell (bovine leukocytes) specific; to define the relationships between Lkt binding to the receptor, calcium elevation, and cytolysis; and to determine whether a correlation exists between Lkt receptor expression and the magnitude of target cell cytolysis. We compared Lkt-induced cytolysis in neutrophils from control calves and from calves with bovine leukocyte adhesion deficiency (BLAD), because neutrophils from BLAD-homozygous calves exhibit reduced β2 integrin expression. The results demonstrate for the first time that Lkt binds to bovine CD11a and CD18 (lymphocyte function-associated antigen 1 [LFA-1]). The binding was abolished by anti-CD11a or anti-CD18 monoclonal antibody (MAb). Lkt-induced calcium elevation in bovine alveolar macrophages (BAMs) was inhibited by anti-CD11a or anti-CD18 MAb (65 to 94% and 37 to 98%, respectively, at 5 and 50 Lkt units per ml;P< 0.05). Lkt-induced cytolysis in neutrophils and BAMs was also inhibited by anti-CD11a or anti-CD18 MAb in a concentration-dependent manner. Lkt bound to porcine LFA-1 but did not induce calcium elevation or cytolysis. In neutrophils from BLAD calves, Lkt-induced cytolysis was decreased by 44% compared to that of neutrophils from control calves (P< 0.05). These results indicate that LFA-1 is a Lkt receptor, Lkt binding to LFA-1 is not target cell specific, Lkt binding to bovine LFA-1 correlates with calcium elevation and cytolysis, and bovine LFA-1 expression correlates with the magnitude of Lkt-induced target cell cytolysis.

Object The decline in cranial nerve morbidity after radiosurgery for vestibular schwannoma (VS) correlates with dose reduction and other technical changes to this procedure. The effect these changes have had on tumor control has not been well documented. Methods The authors performed a retrospective review of 293 patients with VSs who underwent radiosurgery between 1990 and 2004 and had a minimum of 24 months of imaging follow-up (90% of the entire series). The median radiation dose to the tumor margin was 13 Gy. Treatment failure was defined as progressive tumor enlargement noted on 2 or more imaging studies. The mean postradiosurgical follow-up was 60.9 ± 32.5 months. Results Tumor growth was noted in 15 patients (5%) at a median of 32 months after radiosurgery. Radiographically demonstrated tumor control was 96% at 3 years and 94% at 7 years after radiosurgery. Univariate analysis revealed 2 factors that correlated with failed radiosurgery for VS: an increasing number of isocenters (p = 0.03) and tumor margin radiation doses ≤ 13 Gy (p = 0.02). Multivariate analysis showed that only an increasing number of isocenters correlated with failed VS radiosurgery (hazard ratio 1.1, 95% CI 1.02–1.32, p < 0.05). The tumor margin radiation dose (p = 0.22) was not associated with tumor growth after radiosurgery. Conclusions Distortion of stereotactic MR imaging coupled with increased radiosurgical conformality and progressive dose reduction likely caused some VSs to receive less than the prescribed radiation dose to the entire tumor volume.

Object A review of the literature has revealed scant data related to neurosurgical treatment of gravid patients. The authors reviewed their experience with the neurosurgical treatment of pregnant women to better characterize the optimal management strategies for intracranial pathological entities in this population. Methods Between July 1969 and July 2005, 34 patients with documented pregnancy and concomitant intracranial pathological entities were treated at the authors' institution. The average age of the gravid patients at presentation was 27 ± 6 years. Twelve patients harbored vascular and 14 patients harbored neoplastic lesions. Four gravid patients suffered from traumatic intracranial hemorrhage, 2 had primary intracerebral hemorrhage, and 2 had hydrocephalus. The medical records of these patients were reviewed to assess the outcome for the mothers and fetuses. Results Nineteen pregnant patients (56%) underwent a neurosurgical procedure after induction of general anesthesia. Of these, 14 (74%) underwent craniotomies for clipping/resection of their lesion, 2 (10%) underwent stereotactic biopsies, and 3 (16%) underwent CSF shunting procedures. Three patients (9%) delivered by cesarean section followed by their neurosurgical procedure, and 5 (15%) underwent therapeutic abortion preoperatively to allow for radiation therapy early in their pregnancy (4 of these patients underwent surgery prior to their therapeutic abortion). Eleven patients (32%) were treated nonoperatively while pregnant, and 3 of these received their treatment after delivery. There was no operative maternal mortality or permanent morbidity. The fetuses did not suffer from any complications related to the mother's neurosurgical procedure. Conclusions Based on the authors' experience and a review of the literature, surgery for intracranial lesions in pregnant patients is generally well tolerated by both mother and fetus. Preoperative delivery by cesarean section of term or near-term babies is reasonable. Some patients treated conservatively may deteriorate and require an operation.

Herpes zoster ophthalmicus (HZO) with post-herpetic neuralgia (PHN) and giant cell arteritis (GCA) are two diseases more commonly seen in the elderly population. Each has potentially serious and preventable visual complications by differing mechanisms. Treatments for the two diseases differ. Antiviral medications are used in HZO and high-dose corticosteroids in GCA. These two entities could potentially coexist in the same patient, leading to a complicated diagnostic scenario where a potentially treatable disease could be overlooked. Here, we report a patient who was suffering from PHN following zoster ophthalmicus who developed GCA within a time frame suggesting a potential pathogenic association with the reactivation of latent varicella zoster virus (VZV). This association could be either direct with viral vessel infiltration leading to the arteritis or by an indirect dysimmune route. A pathophysiological association with VZV leading to the development of GCA is proposed.

Drugs that inhibit a distinct form of γ-secretase may be useful in treating Alzheimer's disease without causing harmful side effects.

A series of 103 acute fractures of the coronoid process of the ulna in 101 patients was reviewed to determine their frequency. The Regan-Morrey classification, treatment, associated injuries, course and outcomes were evaluated. Of the 103 fractures, 34 were type IA, 17 type IB, ten type IIA, 19 type IIB, ten type IIIA and 13 type IIIB. A total of 44 type-I fractures (86%) were treated conservatively, while 22 type-II (76%) and all type-III fractures were managed by operation. At follow-up at a mean of 3.4 years (1 to 8.9) the range of movement differed significantly between the types of fracture (p = 0.002). Patients with associated injuries had a lower Mayo elbow performance score (p = 0.03), less extension (p = 0.03), more pain (p = 0.007) and less pronosupination (p = 0.004), than those without associated injuries. The presence of a fracture of the radial head had the greatest effect on outcome. An improvement in outcome relative to that of a previous series was noted, perhaps because of more aggressive management and early mobilisation. While not providing complete information about the true details of a fracture and its nature, the Regan-Morrey classification is useful as a broad index of severity and prognosis.

Background— Better insight into the psychosocial factors associated with prehospital delays in seeking care for acute coronary syndromes is needed to inform the design of future interventions. Delay in presenting for care after the onset of symptoms is common, limits the potential benefit of acute reperfusion, and has not been reduced by interventions tested thus far. Methods and Results— Seven hundred ninety-six patients with suspected ischemic heart disease scheduled for clinically indicated imaging stress tests completed questionnaires concerning psychological distress and attachment styles (worthiness to receive care, trustworthiness of others to provide care). The primary dependent variable for this study was response to a question from the rapid early action for coronary treatment trial concerning intention to “wait until very sure” before seeking care for a possible “heart attack.” Responses to this question were strongly associated with actual emergency department-reported and self-reported care delay in the rapid early action for coronary treatment trial. In multivariable ordinal regression models, a more negative view of the trustworthiness of others, greater physical limitations from angina, and no previous revascularization were independently associated with increased intention to wait to seek care for a myocardial infarction. Intention to wait was not associated with inducible ischemia or self-perceived risk of myocardial infarction. Conclusions— Intention to delay seeking care for acute coronary syndromes is associated with a patient’s view of the trustworthiness of others, previous experience with revascularization, and functional limitations, even after adjustment for objective and perceived acute coronary syndromes risk. These findings provide insight into novel factors contributing to longer delay times and may inform future interventions to reduce delay time.

Abstract Detailed genomic studies have shown that cytogenetic abnormalities contribute to multiple myeloma (MM) pathogenesis and disease progression. Nevertheless, little is known about the characteristics of MM at the epigenetic level and specifically how microRNAs regulate MM progression in the context of the bone marrow milieu. Therefore, we performed microRNA expression profiling of bone marrow derived CD138+ MM cells versus their normal cellular counterparts and validated data by qRT-PCR. We identified a MM-specific microRNA signature characterized by down-expression of microRNA-15a/-16 and overexpression of microRNA-222/-221/-382/-181a/-181b (P < .01). We investigated the functional role of microRNA-15a and -16 and showed that they regulate proliferation and growth of MM cells in vitro and in vivo by inhibiting AKT serine/threonine-protein-kinase (AKT3), ribosomal-protein-S6, MAP-kinases, and NF-κB-activator MAP3KIP3. Moreover, miRNA-15a and -16 exerted their anti-MM activity even in the context of the bone marrow milieu in vitro and in vivo. These data indicate that microRNAs play a pivotal role in the biology of MM and represent important targets for novel therapies in MM.