2-methylene-(20S,25S)-19,27-dinor-(22E)-vitamin D analogs

This invention discloses 2-methylene-(20S,25S)-19,27-dinor-(22E)-vitamin D analogs, and specifically 2-methylene-(20S,25S)-19,27-dinor-(22E)-1.alpha.,25-dihydroxyvitamin D.sub.3, and pharmaceutical uses therefor. This compound exhibits pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent and for the treatment of skin diseases such as psoriasis as well as skin conditions such as wrinkles, slack skin, dry skin and insufficient sebum secretion. This compound also has little, if any, calcemic activity and therefore may be used to treat autoimmune disorders or inflammatory diseases in humans as well as renal osteodystrophy. This compound may also be used for the treatment or prevention of obesity

Hand ischemia associated with elbow trauma in children

ObjectivesPrevious observational studies suggest that children with hand ischemia following elbow trauma can be safely observed if Doppler signals are present in the wrist arteries (pink pulseless hand, PPH). Nonoperative management of PPH is predicated on the assumption that PPH results from local arterial spasm, but the mechanism of arterial compromise has not been investigated. We hypothesized that PPH signifies a brachial artery injury that requires surgical repair.MethodsRetrospective review of operations performed on children with hand ischemia following elbow trauma at a level I trauma center pediatric hospital.ResultsBetween 2003 and 2010, 12 children (seven males, mean age 7.4 years) underwent brachial artery exploration for hand ischemia following elbow trauma (11 supracondylar fractures, one elbow dislocation) due to falls (n = 10) or motor vehicle crashes (n = 2). At presentation, three subjects had normal radial pulses, eight subjects had Doppler signals but no palpable pulses, and one had weak Doppler flow with advanced hand ischemia. Six of the nine subjects without palpable pulses also had neurosensory changes. All 12 subjects underwent brachial artery exploration either initially (n = 2) or following orthopedic fixation (n = 10) due to persistent pulselessness. At operation, eight of 12 patients (67%) had focal brachial artery thrombosis due to intimal flaps, and four had brachial artery and median nerve entrapment within the pinned fracture site. At discharge, all 12 subjects had palpable radial pulses, but three with entrapment had dense median nerve deficits. One of the three subjects with dense neurologic deficit had complete recovery of neurologic function at ten months. The other two subjects had residual median nerve deficits with partial recovery at 5 and 6 months follow-up, respectively. No patient developed Volkman's contracture.ConclusionsBrachial artery injuries should be anticipated in children with hand ischemia associated with elbow trauma. Neurovascular entrapment at the fracture site is a possible complication of orthopedic fixation. Absence of palpable wrist pulses after orthopedic fixation should prompt immediate brachial artery exploration. PPH should not be considered a consequence of arterial spasm in these patients

Accuracy and utility of three-dimensional contrast-enhanced magnetic resonance angiography in planning carotid stenting

BackgroundContrast-enhanced magnetic resonance angiography (CE-MRA) is a proven diagnostic tool for the evaluation of carotid stenosis; however, its utility in planning carotid artery stenting (CAS) has not been addressed. This study assessed the accuracy of three-dimensional CE-MRA as a noninvasive screening tool, compared with digital subtraction angiography (DSA), for evaluating carotid and arch morphology before CAS.MethodsIn a series of 96 CAS procedures during a 2-year period, CE-MRAs and DSAs with complete visualization from the aortic arch to the intracranial circulation were obtained before CAS in 60 patients. Four additional patients, initially considered potential candidates for CAS, were also evaluated with CE-MRA and DSA. The two-by-two table method, receiver operating characteristic curve, and Bland-Altman analyses were used to characterize the ability of CE-MRA to discriminate carotid and arch anatomy, suitability for CAS, and degree of carotid stenosis.ResultsThe sensitivity and specificity of CE-MRA were, respectively, 100% and 100% to determine CAS suitability, 87% and 100% to define aortic arch type, 93% and 100% to determine severe carotid tortuosity, and 75% and 98% to detect ulcerated plaques. CE-MRA had 87% sensitivity and 100% specificity for the detection of carotid stenosis ≥80%. The accuracy of CE MRA to determine optimal imaging angles and stent and embolic protection device sizes was >90%. The operative technique for CAS was altered because of the findings of preoperative CE-MRA in 22 procedures (38%). The most frequent change in the operative plan was the use of the telescoping technique in 11 cases (18%). CAS was aborted in four patients (5%) due to unfavorable anatomy identified on CE-MRA, including prohibitive internal carotid artery tortuosity (n = 1), long string sign of the internal carotid artery (n = 2), and concomitant intracranial disease (n = 1). Among patients considered suitable for CAS by CE-MRA, technical success was 100%, and the 30-day stroke/death rate was 1.6%.ConclusionsContrast-enhanced magnetic resonance angiography of the arch and carotid arteries is accurate in determining suitability for CAS and may alter the operative technique. Certain anatomic contraindications for CAS may be detected without DSA. Although CE-MRA is less accurate to estimate the degree of stenosis, it can accurately predict imaging angles, and stent and embolic protection device size, which may facilitate safe and expeditious CAS

Defining the type of surgeon volume that influences the outcomes for open abdominal aortic aneurysm repair

ObjectivePrior studies have reported improved clinical outcomes with higher surgeon volume, which is assumed to be a product of the surgeon's experience with the index operation. We hypothesized that composite surgeon volume is an important determinant of outcome. We tested this hypothesis by comparing the impact of operation-specific surgeon volume versus composite surgeon volume on surgical outcomes, using open abdominal aortic aneurysm (AAA) repair as the index operation.MethodsThe Nationwide Inpatient Sample was analyzed to identify patients undergoing open AAA repairs for 2000 to 2008. Surgeons were stratified into deciles based on annual volume of open AAA repairs (“operation-specific volume”) and overall volume of open vascular operations (“composite volume”). Composite volume was defined by the sum of several open vascular operations: carotid endarterectomy, aortobifemoral bypass, femoral-popliteal bypass, and femoral-tibial bypass. Multiple logistic regression analyses were used to examine the relationship between surgeon volume and in-hospital mortality for open AAA repair, adjusting for both patient and hospital characteristics.ResultsBetween 2000 and 2008, an estimated 111,533 (95% confidence interval [CI], 102,296-121,232) elective open AAA repairs were performed nationwide by 6,857 surgeons. The crude in-hospital mortality rate over the study period was 6.1% (95% CI, 5.6%-6.5%). The mean number of open AAA repairs performed annually was 2.4 operations per surgeon. The mean composite volume was 5.3 operations annually. As expected, in-hospital mortality for open AAA repair decreased with increasing volume of open AAA repairs performed by a surgeon. Mortality rates for the lowest and highest deciles of surgeon volume were 10.2% and 4.5%, respectively (P < .0001). A similar pattern was observed for composite surgeon volume, as the mortality rates for the lowest and highest deciles of composite volume were 9.8% and 4.8%, respectively (P < .0001). After adjusting for patient and hospital characteristics, increasing composite surgeon volume remained a significant predictor of lower in-hospital mortality for open AAA repair (odds ratio, 0.994; 95% CI, .992-.996; P < .0001), whereas increasing volume of AAA repairs per surgeon did not predict in-hospital deaths.ConclusionsThe current study suggests that composite surgeon volume—not operation-specific volume—is a key determinant of in-hospital mortality for open AAA repair. This finding needs to be considered for future credentialing of surgeons

Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis

Background. Without strong evidence of benefit, the use of carotid endarterectomy for prophylaxis against stroke rose dramatically until the mid-1980s, then declined. Our investigation sought to determine whether carotid endarterectomy reduces the risk of stroke among patients with a recent adverse cerebrovascular event and ipsilateral carotid stenosis. Method. We conducted a randomized trial at 50 clinical centers throughout the United States and Canada, in patients in two predetermined strata based on the severity of carotid stenosis—30 to 69 percent and 70 to 99 percent. We report here the results in the 659 patients in the latter stratum, who had had a hemispheric or retinal transient ischemic attack or a nondisabling stroke within the 120 days before entry and had stenosis of 70 to 99 percent in the symptomatic carotid artery. All patients received optimal medical care, including antiplatelet therapy. Those assigned to surgical treatment underwent carotid endarterectomy performed by neurosurgeons or vascular surgeons. All patients were examined by neurologists 1, 3, 6, 9, and 12 months after entry and then every 4 months. End points were assessed by blinded, independent case review. No patient was lost to follow-up. Results. Life-table estimates of the cumulative risk of any ipsilateral stroke at two years were 26 percent in the 331 medical patients and 9 percent in the 328 surgical patients—an absolute risk reduction (±SE) of 17±3.5 percent (P\u3c0.001). For a major or fatal ipsilateral stroke, the corresponding estimates were 13.1 percent and 2.5 percent — an absolute risk reduction of 10.6±2.6 percent (P\u3c0.001 ). Conclusion. Carotid endarterectomy was still found to be beneficial when all strokes and deaths were included in the analysis (P\u3c0.001). Carotid endarterectomy is highly beneficial to patients with recent hemispheric and retinal transient ischemic attacks or nondisabling strokes and ipsilateral high-grade stenosis (70 to 99 percent) of the internal carotid artery. (N Engl J Med 1991; 325:445–53.). © 1991, Massachusetts Medical Society. All rights reserved

Decreased Serologic Response in Vaccinated Military Recruits during 2011 Correspond to Genetic Drift in Concurrent Circulating Pandemic A/H1N1 Viruses

Population-based febrile respiratory illness surveillance conducted by the Department of Defense contributes to an estimate of vaccine effectiveness. Between January and March 2011, 64 cases of 2009 A/H1N1 (pH1N1), including one fatality, were confirmed in immunized recruits at Fort Jackson, South Carolina, suggesting insufficient efficacy for the pH1N1 component of the live attenuated influenza vaccine (LAIV).To test serologic protection, serum samples were collected at least 30 days post-vaccination from recruits at Fort Jackson (LAIV), Parris Island (LAIV and trivalent inactivated vaccine [TIV]) at Cape May, New Jersey (TIV) and responses measured against pre-vaccination sera. A subset of 78 LAIV and 64 TIV sera pairs from recruits who reported neither influenza vaccination in the prior year nor fever during training were tested by microneutralization (MN) and hemagglutination inhibition (HI) assays. MN results demonstrated that seroconversion in paired sera was greater in those who received TIV versus LAIV (74% and 37%). Additionally, the fold change associated with TIV vaccination was significantly different between circulating (2011) versus the vaccine strain (2009) of pH1N1 viruses (ANOVA p value = 0.0006). HI analyses revealed similar trends. Surface plasmon resonance (SPR) analysis revealed that the quantity, IgG/IgM ratios, and affinity of anti-HA antibodies were significantly greater in TIV vaccinees. Finally, sequence analysis of the HA1 gene in concurrent circulating 2011 pH1N1 isolates from Fort Jackson exhibited modest amino acid divergence from the vaccine strain.Among military recruits in 2011, serum antibody response differed by vaccine type (LAIV vs. TIV) and pH1N1 virus year (2009 vs. 2011). We hypothesize that antigen drift in circulating pH1N1 viruses contributed to reduce vaccine effectiveness at Fort Jackson. Our findings have wider implications regarding vaccine protection from circulating pH1N1 viruses in 2011-2012

Autologous deep vein reconstruction of infected thoracoabdominal aortic patch graft

AbstractGraft infection remains a serious complication of prosthetic aortic repair. Infection of thoracoabdominal aortic prosthetic grafts, in particular, is a significant clinical challenge and is associated with high mortality. We report successful in situ reconstruction of an infected thoracoabdominal aortic prosthetic patch graft with autogenous superficial femoral vein. To our knowledge, this is the first such case described in the North American and English language surgical literature. At 24-month follow-up the patient remains well, with no evidence of sepsis or graft complication at clinical and radiologic assessment

Endothelial Linings in Prosthetic Vascular Grafts

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73894/1/j.1749-6632.1987.tb33036.x.pd