Preparation and ring-opening reactions of N-diphenylphosphinyl vinyl aziridines.

Predominantly (E)-N-diphenylphosphinyl vinyl aziridines are prepared by a reaction of N-diphenylphosphinyl imines with α-bromoallyllithium in the presence of freshly fused ZnCl2. These aziridines undergo a ring-opening reaction with a variety of carbon and heteronucleophiles, in good yield, and generally with good regioselectivity.

Scraper reduction and "imposed form" at the Lower Palaeolithic site of High Lodge, England.

This paper investigates patterns of scraper retouch at the Lower Palaeolithic site of High Lodge, England. The unifacial scrapers from High Lodge are intensively retouched tools with regular and complex shapes that have been routinely interpreted as evidence of intentional design. The primary aim is to determine whether the different scraper types identified in the assemblage represent discrete and discontinuous implement categories made according to fixed designs, or rather, points or stages along one or more reduction continuums. To achieve this, we apply a range of quantitative measures of artifact reduction to all complete single, double, convergent, and transverse scrapers from the site (n=165). Our results indicate that morphological and typological diversity in the High Lodge scraper assemblage can be parsimoniously explained as a result of both the extent to which implements were resharpened during use and subtle variability in the nature of blank forms selected for retouch. Accordingly, we critique the notion that high levels of morphological complexity in retouched Lower Palaeolithic tool types necessarily reflect the imposition of preconceived forms on stones.

Catheter-related right atrial thrombus and pulmonary embolism: a case report and systematic review of the literature.

Central venous catheters (CVCs) are commonly used in clinical practice. One of the foremost complications associated with their use is the potential for symptomatic or asymptomatic thrombosis. CVC thrombosis, in turn, may not only result in vascular and catheter occlusion but also infection, pulmonary embolism, and formation of right heart thromboemboli. Thrombi within cardiac chambers are associated with an increased risk of mortality due to their potential for embolization to the pulmonary vasculature. We describe the case of a 77-year-old man, who was successfully thrombolyzed following detection of a right atrial thrombus and hemodynamically significant pulmonary embolism resulting from thrombus formation on the tip of a peripherally inserted central catheter (PICC). The present article is the first report of a PICC-related right atrial thrombus in an adult treated with thrombolysis. A systematic review of the literature suggests that the true incidence of this complication may be underestimated because the diagnosis may not be considered in asymptomatic and symptomatic patients, or may be missed by transthoracic echocardiography. The present case highlights the importance of maintaining a high index of suspicion for thromboembolic complications and heparin-induced thrombocytopenia in patients with CVCs or a PICC. It also underscores the important role of transesophageal echocardiography and thrombolysis in the diagnosis and management, respectively, of right heart thromboemboli with associated pulmonary embolism.

A critical review of thromboembolic complications associated with central venous catheters.

PURPOSE: Central venous catheters (CVC) are commonly used in critical care. While thrombosis is a well-recognized and frequent complication associated with their use, CVC-related thromboembolic complications, including pulmonary embolism (PE) and right heart thromboembolism (RHTE), occur less frequently and often evade diagnosis. Little information exists to guide clinicians in the diagnosis and management of CVC-related thromboembolic complications. SOURCE: We critically review and synthesize the literature highlighting the incidence of CVC-related thrombosis. We highlight the risk for developing thromboembolic complications and provide approaches to diagnosing and managing RHTE. PRINCIPLE FINDINGS: The incidence of CVC-related thrombosis varies depending on patient, site, instrument, and infusate-related factors. Central venous catheters-related thrombosis represents an important source of morbidity and mortality for affected patients. Pulmonary embolism occurs in approximately 15% of patients with CVC-related upper extremity deep venous thrombosis (UEDVT). More frequent use of transesophageal echocardiography, in patients with suspected and confirmed PE, has resulted in increased detection of RHTE. While it is recognized that the occurrence of RHTE, in association with PE, increases mortality, the optimal strategy for their management has not been established in a clinical trial. CONCLUSION: Central venous catheter-related thrombosis occurs frequently and represents an important source of morbidity and mortality for affected patients. Our review supports that surgery and thrombolysis have both been demonstrated to enhance survival in patients with RHTE and PE. However, important patient, clot, and institutional considerations mandate that treatment for patients with RHTE and PE be individualized.

Autonomic function is impaired in elderly stroke survivors.

BACKGROUND AND PURPOSE: Impaired autonomic function is common in the acute poststroke phase but little is known about the longer term effects, particularly in older people. We sought to determine if autonomic function is impaired after stroke recovery in older patients. METHODS: A cross-sectional case-control study comparing autonomic function in 76 nondemented stroke patients with 70 community-living controls aged older than 75 years. RESULTS: Cases were assessed on average 9 months after stroke. From power spectral analysis of heart rate variability, stroke patients had lower total (P=0.032) and low-frequency (P=0.014) spectral densities and impaired baroreflex sensitivity (alpha low-frequency baroreflex sensitivity, P=0.006). From a series of cardiovascular autonomic reflex tests, heart rate variation during forced respiration, Valsalva ratio, and blood pressure overshoot during Valsalva maneuver were significantly lower in stroke patients (P=0.003, <0.001, and 0.027, respectively). Blood pressure response to isometric exercise was significantly exaggerated in stroke patients (P=0.007). CONCLUSIONS: Cardiovascular autonomic function is impaired long after the index event in stroke survivors. Impaired autonomic function may increase the risk of all-cause mortality and cardiovascular mortality in older stroke survivors.

Familial neurocardiogenic (vasovagal) syncope.

Vasovagal syncope (VSS) is an exaggerated tendency towards the common faint caused by a sudden and profound hypotension with or without bradycardia. The etiology of VVS is unknown though several lines of evidence indicate central and peripheral abnormalities of sympathetic function. Studies however indicate a strong heritable component to the etiology of VVS in over 20% of cases. Here, we report the findings from a family that shows apparently autosomal dominant VVS in at least three generations. Clinical findings included an absence of any discernible cardiac or autonomic abnormalities and reproducible hypotension on tilt table testing in affected family members.

Liver transplantation from non-heart-beating donors: current status and future prospects.

Liver transplantation is the treatment of choice for many patients with acute and chronic liver failure, but its application is limited by a shortage of donor organs. Donor organ shortage is the principal cause of increasing waiting lists, and a number of patients die while awaiting transplantation. Non-heart-beating donor (NHBD) livers are a potential means of expanding the donor pool. This is not a new concept. Prior to the recognition of brainstem death, organs were retrieved from deceased donors only after cardiac arrest. Given the preservation techniques available at that time, this restricted the use of extrarenal organs for transplantation. In conclusion, after establishment of brain death criteria, deceased donor organs were almost exclusively from heart-beating donors (HBDs). To increase organ availability, there is now a resurgence of interest in NHBD liver transplantation. This review explores the basis for this and considers some of the published results.

Trends in organ preservation.

Organ preservation aims to provide a viable graft with primary function post-transplant. The current basis of preservation for transplantation is static cold storage using specific preservation solutions which minimise cellular swelling and membrane pump activity, thus maintaining cellular ATP levels. The current organ shortage and consequent expansion of donor criteria places even greater reliance on minimising graft injury during preservation. This review focuses on current and future advances in preservation technology. The key areas of advance are additives to preservation solutions, alternatives/adjuncts to preservation solutions including perfluorocarbons. A major area of advance is in the modulation of organs during the storage period. This may be achieved by biochemical additives or genetic manipulation. Machine perfusion technology is improving, and this is discussed together with the recent concept of warm (normothermic) perfusion as an alternative means of preservation. The authors provide an overview over the current methods of organ preservation. Cold storage, effective in the short-term is insufficient for marginal organs, does not allow assessment of viability markers, and provokes ischaemic injury. Potential strategies for minimising ischaemic injury include additives to preservation solutions; the two-layer method with perfluorcarbons and UW solution-at present limited to pancreas preservation; organ modulation; organ preconditioning and genetic modification of organs. In particular, the authors illuminate the potential in a reappraisal of the concept of normothermic perfusion.

Dementia with Lewy bodies.

The objective was to summarize recent findings about the clinical features, diagnosis and investigation of dementia with Lewy (DLB) bodies, together with its neuropathology, neurochemistry and genetics. Dementia with Lewy bodies (DLB) is a primary, neurodegenerative dementia sharing clinical and pathological characteristics with both Parkinson's disease (PD) and Alzheimer's disease (AD). Antiubiquitin immunocytochemical staining, developed in the early 1990s, allowed the frequency and distribution of cortical LBs to be defined. More recently, alpha-synuclein antibodies have revealed extensive neuritic pathology in DLB demonstrating a neurobiological link with other "synucleinopathies" including PD and multiple system atrophy (MSA). The most significant correlates of cognitive failure in DLB appear to be with cortical LB and Lewy neurites (LNs) rather than Alzheimer type pathology. Clinical diagnostic criteria for DLB, published in 1996, have been subjected to several validation studies against autopsy findings. These conclude that although diagnostic specificity is high (range 79- 100%, mean 92%), sensitivity is lower (range 0- 83 %, mean, 49%). Improved methods of case detection are therefore required. Fluctuating impairments in attention, visual recognition and construction are more indicative of DLB than AD. Relative preservation of medial temporal lobe volume on structural MRI and the use of SPECT tracers for regional blood flow and the dopamine transporter are the most reliable current biomarkers for DLB. There are no genetic or CSF tests recommended for the diagnosis of DLB at present. Between 15 and 20% of all elderly demented cases reaching autopsy have DLB, making it the most common cause of degenerative dementia after AD. Exquisite, not infrequently fatal, sensitivity to neuroleptic drugs and encouraging reports of the effects of cholinesterase inhibitors on cognitive, psychiatric and neurological features, mean that an accurate diagnosis of DLB is more than merely of academic interest. Dementia developing late in the course of PD shares many of the same clinical and pathological characteristics.

Mild cognitive impairment and vascular cognitive impairment in stroke patients.

In 150 older stroke patients (>75) without dementia, the proportion of people meeting different criteria for early cognitive impairment varied from 17% to 23% depending upon the individual criteria used. Given this large disparity, prospective studies to clarify the utility of different criteria as a predictor of subsequent dementia are a priority.

Neuropsychological deficits in older stroke patients.

This paper examines the frequency of CIND, the profile of early cognitive deficits in stroke patients, the differences in the profile of cognitive impairment in people with CIND and those with vascular dementia, and the MRI associations of CIND in older stroke patients.

Cognitive decline in a prospectively studied group of stroke survivors, with a particular emphasis on the >75's.

BACKGROUND: Although cognitive decline is frequent after stroke, there has been very little work focussing upon older age groups, in whom the majority of strokes occur. OBJECTIVE: To determine whether cognitive decline is more common in older (>75) compared to younger (<75) stroke survivors. METHOD: A cohort of 360 stroke survivors of all ages from a stroke register in Newcastle, UK, were assessed prospectively at 3 time points over 1 year with a standardized battery. Dementia was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria. RESULTS: The overall one year prevalence of dementia was 23%, but rose from 7% in the under 65's to 53% in over 85's. People over 75 were significantly more likely to have dementia (Odds Ratio 8.9, 95% Confidence Intervals 4.1-19.1). CONCLUSION: The striking age related increase in the prevalence of dementia has important implications for service planning and clinical management.

Lecithinized superoxide dismutase reduces cold ischemia-induced chronic allograft dysfunction.

BACKGROUND: Chronic renal allograft failure (CAF) is influenced by both allo-dependent and independent factors and is a major cause of graft loss in clinical renal transplantation. We evaluated a novel membrane-bound free radical scavenger, lecithinized superoxide dismutase (lec-SOD), to determine its potential in limiting the harmful effects of ischemia/reperfusion injury on CAF. METHODS: Fisher rat kidneys were stored for either 1 hour or 18 hours in cold Marshall's preservation solution either with or without lec-SOD and transplanted into Lewis recipients. RESULTS: Within 3 days of transplantation, an early inflammatory response involving granulocytes and macrophages was detected in renal allografts exposed to 18 hours cold ischemia that was significantly reduced by preservation with lec-SOD. By 24 weeks post-transplantation, elevated proteinuria and detection of apoptotic cells was observed in kidneys exposed to 18 hours of cold ischemia, that was attenuated by preservation with lec-SOD (P < 0.05). However, up-regulated expression of intracellular adhesion molecule-1 (ICAM-1) and major histocompatibility complex (MHC) Class II together with a T lymphocyte infiltration were observed at 24 weeks that was not prevented by preservation with lec-SOD. CONCLUSIONS: These results demonstrate that ischemia/reperfusion injury, apoptotic cell death and allo-immune responses may be exacerbated by cold ischemia and accelerate the development of CAF. Preservation with lec-SOD may protect against the early damage induced by cold ischemia and reperfusion injury.