Archive for June, 2006

Neural stem cell systems: diversities and properties after transplantation in animal models of diseases.

Sunday, June 18th, 2006
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Neural stem cell systems: diversities and properties after transplantation in animal models of diseases.

Brain Pathol. 2006 Apr;16(2):143-54

Authors: Conti L, Reitano E, Cattaneo E

Currently available effective treatments of the diseased or damaged central nervous system (CNS) are restricted to a limited pharmacological relief of symptoms or those given to avoid further damage. Therefore the search is on for treatments that can restore function in the CNS. During recent years replacement of damaged neurons by cell transplantation is being enthusiastically explored as a potential treatment for many neurodegenerative diseases, stroke and traumatic brain injury. Several references in both scientific journals and popular newspapers concerning different types of cultured stem cells, potentially exploitable to treat pathological conditions of the brain, raise important questions pertinent to the fundamental and realistic differences between grafts of primary neural cells and the transplantation of in vitro expanded neural stem cells (NSCs). Our aim is to review the available information on the grafting of different NSC types into the adult rodent brain, focusing on critical aspects for the development of clinical therapies to replace damaged neurons.

PMID: 16768755 [PubMed - in process]

Antiplatelet therapy in peripheral occlusive arterial disease.

Sunday, June 18th, 2006
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Antiplatelet therapy in peripheral occlusive arterial disease.

ANZ J Surg. 2006 May;76(5):364-72

Authors: Wong S, Appleberg M, Lewis DR

BACKGROUND: Antiplatelet therapy (APT) in patients with peripheral occlusive arterial disease (POAD) may reduce cardiovascular (CV) morbidity and mortality by inhibiting atherothrombosis. This article reviews the current evidence for APT in patients with stable POAD and in patients undergoing revascularization procedures for POAD. METHODS: A Medline and Pubmed literature search (January 1966 to February 2003) was conducted to identify articles relating APT and POAD. Manual cross referencing was also used. RESULTS AND CONCLUSIONS: Meta-analyses suggest that APT (most commonly aspirin) in patients with stable POAD significantly reduces the incidence of nonfatal stroke, myocardial infarction and CV death. However, this conclusion is based on subset analysis of data predominantly involving patients with coronary and cerebrovascular atherosclerosis. There is a little direct evidence for the use of aspirin in patients with isolated POAD, but in practice, aspirin remains the most commonly used antiplatelet agent as high rates of coronary and cerebrovascular diseases are observed in this patient population. For patients with POAD without additional indicators of vascular risk, the protective effect of aspirin is unclear and dependent on the balance of risks and benefits in the individual patient. For patients undergoing peripheral revascularization, ticlopidine and aspirin in combination with dipyridamole are effective in maintaining patency after bypass procedures and following angioplasty/femoral endarterectomy. The efficacy of thienopyridines in peripheral angioplasty is uncertain, and the optimum timing and duration of APT relative to intervention are not known.

PMID: 16768698 [PubMed - in process]

Outcomes of a contemporary amputation series.

Sunday, June 18th, 2006
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Outcomes of a contemporary amputation series.

ANZ J Surg. 2006 May;76(5):300-5

Authors: Lim TS, Finlayson A, Thorpe JM, Sieunarine K, Mwipatayi BP, Brady A, Abbas M, Angel D

BACKGROUND: The aim of this study was to determine the outcomes of a contemporary amputation series. METHODS: A retrospective audit of 87 cases of major lower limb amputation from January 2000 to December 2002 from the Department of Vascular Surgery, Royal Perth Hospital, was conducted. RESULTS: The mean age of the study population was 70.1 +/- 14.3 years; the male : female ratio was 3.35:1. Comorbid problems included diabetes (49.4%), smoking (81.6%), hypertension (77.0%), ischaemic heart disease (58.6%), stroke (25.3%), raised creatinine level (34.5%) and chronic airway limitation (25.3%). Preamputation vascular reconstructive procedures were common, 34.5% in a previous admission and 23.0% in the same admission. The main indication was critical limb ischaemia (75.9%) followed by diabetic infection (17.2%). There were 51 below-knee (58.6%), 5 through-knee (5.7%) and 31 above-knee (35.6%.) amputations. The below-knee amputation to above-knee amputation ratio was 1.65:1. The overall wound infection rate was 26.4%; the infection rates for below-knee (29.4%) and above-knee (22.6%) amputation did not differ significantly (P = 0.58). Revision rates were 17.6% for below-knee, 20% for through-knee and none for above-knee amputations. Twenty patients (23.0%) underwent subsequent contralateral amputation. Thirty-nine patients (44.8%) were selected as suitable for a prosthesis by a rehabilitation physician; 31 (79.5%) used the prosthesis both indoors and outdoors and 6 (15.4%) used it indoors only within 3 months. Cumulative mortality at 30 days, 6 months, 12 months and 24 months was 10.1, 28.7, 43.1 and 51.7%, respectively. CONCLUSION: This series agrees with the current published work in finding that patients undergoing major lower limb amputation are older, with a high prevalence of comorbid conditions. Successful prosthesis rehabilitation depends on patient selection and a multidisciplinary approach. Despite a low immediate mortality, the overall long-term results of lower limb amputation remain dismal.

PMID: 16768686 [PubMed - in process]

Low-dose thalidomide plus monthly high-dose oral dexamethasone (Thali-Dexa): results, prognostic factors and side effects in eight patients previously treated with multiple myeloma.

Sunday, June 18th, 2006
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Low-dose thalidomide plus monthly high-dose oral dexamethasone (Thali-Dexa): results, prognostic factors and side effects in eight patients previously treated with multiple myeloma.

J Exp Clin Cancer Res. 2003 Dec;22(4 Suppl):129-33

Authors: Bemardeschi P, Dentico P, Rossi S, Fiorentini G, Giustarini G, Turano E

Thalidomide is active both as single agent and in combination-therapy against refractory or relapsing multiple myeloma. Eigth patients previously treated were given Thalidomide 100mg/daily plus Dexametasone 40mg/daily for four days each month (Thali-Dexa) and followed for response, prognostic factors and side effects. Two patients had early death (one from massive cerebral ischemic stroke, the other from dementia and progressive renal failure), one patient progressed during Thali-Dexa (thalidomide 200mg) and was rescued with chemotherapy, two patients required increasing thalidomide dosage (to 200 and 400mg, respectively) because of progressive disease, three patients had stable disease remission lasting from 4m+ to 16m+. Thali-Dexa is a useful agent but age and vascular/metabolic diseases may increase the risk of severe side effects. Early decrease in erythrocyte sedimentation rate seems to correlate with better disease control.

PMID: 16767919 [PubMed - in process]

Effect of using local arterial input functions on cerebral blood flow estimation.

Sunday, June 18th, 2006
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Effect of using local arterial input functions on cerebral blood flow estimation.

J Magn Reson Imaging. 2006 Jun 9;

Authors: Lorenz C, Benner T, Lopez CJ, Ay H, Zhu MW, Aronen H, Karonen J, Liu Y, Nuutinen J, Sorensen AG

PURPOSE: To investigate a previously developed method for perfusion-weighted MRI (PWI) cerebral blood flow (CBF) estimation that uses local arterial input functions (AIFs) in stroke patients, and determine its ability to correct delay and/or dispersion (D/D) errors. MATERIALS AND METHODS: Analysis was performed on dynamic susceptibility contrast data from 36 stroke patients, and CBF maps were calculated with global- and local-AIF techniques using standard SVP based methods. The ratios of these maps were calculated and the mean ratios were calculated for voxels with both normal and abnormal time to peak or width. The locations of the voxels with high locally-defined to globally-defined CBF ratios were also mapped and the average underlying concentration-time curves for these voxels were calculated. RESULTS: The ratio of CBF estimates based on local AIFs to global AIFs was on average increased for D/D voxels. The voxels in which this ratio was high were commonly concentrated in the ipsilateral hemisphere, and these voxels also displayed underlying concentration-time curves that showed delay or dispersion. Conversely, there were no such findings based on high globally-defined to locally-defined CBF ratios. CONCLUSION: The local-AIF technique results in an increase in the calculated CBF values for tissues with D/D, consistent with a reduction in the errors associated with D/D. J. Magn. Reson. Imaging 2006. (c) 2006 Wiley-Liss, Inc.

PMID: 16767708 [PubMed - as supplied by publisher]

The Italian multicenter observational study on post-stroke depression (DESTRO).

Sunday, June 18th, 2006
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The Italian multicenter observational study on post-stroke depression (DESTRO).

J Neurol. 2006 May;253(5):556-62

Authors: Paolucci S, Gandolfo C, Provinciali L, Torta R, Toso V,

Despite growing information, questions still surround various aspects of post-stroke depression (PSD). The Italian multicenter observational study Destro was designed to help clarify in a large sample the frequency and clinical impact of PSD. A total of 53 centers consecutively admitted 1064 patients with ischemic or hemorrhagic stroke, assessing them periodically in the first 9 months after the event. Patients with depression were followed for two years. Depression was diagnosed on clinical examination, verbal (Beck Depression Inventory) and non-verbal rating systems (Visual Analog Mood Scale), identifying the nosographic condition attributable to the mental state. The patient’s clinical history, residual independence, and post-ictus quality of life were also taken into account. PSD was detected in 383 patients (36 %), most of whom had minor depression (80.17 %), with dysthymia, rather than major depression and adaptation disorder. About 80% developed depression within three months of the stroke. Cases with later onset tended to have less severe symptoms. Risk factors were a history of depression, severe disability, previous stroke and female sex, but not the type and site of the vascular lesion. PSD was not correlated with any increase in mortality or cerebrovascular recurrences, but these patients had lower autonomy and quality of life ratings. In conclusion, patients should be close observed in the first few weeks after a stroke in order to check for depression,which is more likely in those with clear risk factors and may spoil their quality of life.

PMID: 16767539 [PubMed - in process]

Spontaneous splenic infarction associated with sumatriptan use.

Sunday, June 18th, 2006
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Spontaneous splenic infarction associated with sumatriptan use.

J Headache Pain. 2006 Jun 15;

Authors: Arora A, Arora S

Triptans are specific agonists of the serotonergic 5-HT(1B/1D) receptors that have increasingly been used in the treatment of migraine and cluster headaches. Though they are generally considered safe, there have been a few reports of myocardial infarction and stroke associated with triptan use. We report a patient who developed spontaneous splenic infarction after the use of sumatriptan for the treatment of migraine headache.

PMID: 16767537 [PubMed - as supplied by publisher]

Comorbid neuropathologies in migraine.

Sunday, June 18th, 2006
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Comorbid neuropathologies in migraine.

J Headache Pain. 2006 Jun 15;

Authors: Sacco S, Olivieri L, Bastianello S, Carolei A

The identification of comorbid disorders in migraineurs is important since it may impose therapeutic challenges and limit treatment options. Moreover, the study of comorbidity might lead to improve our knowledge about causes and consequences of migraine. Comorbid neuropathologies in migraine may involve mood disorders (depression, mania, anxiety, panic attacks), epilepsy, essential tremor, stroke, and white matter abnormalities. Particularly, a complex bidirectional relation exists between migraine and stroke, including migraine as a risk factor for cerebral ischemia, migraine caused by cerebral ischemia, migraine as a cause of stroke, migraine mimicking cerebral ischemia, migraine and cerebral ischemia sharing a common cause, and migraine associated with subclinical vascular brain lesions.

PMID: 16767530 [PubMed - as supplied by publisher]

The influence of comorbidities and complications on discharge function in stroke rehabilitation inpatients.

Sunday, June 18th, 2006
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The influence of comorbidities and complications on discharge function in stroke rehabilitation inpatients.

Eura Medicophys. 2006 Jun;42(2):91-6

Authors: Ferriero G, Franchignoni F, Benevolo E, Ottonello M, Scocchi M, Michail X

AIM: The aims of this prospective study were: 1) to assess the frequency, type and severity of comorbidities (COMs) and complications (COMPLs) in acute stroke patients, according to the weighted comorbidity index (w-CI) of Liu et al. and 2 new indices, respectively COM severity index (COM-SI) and COMPL severity index (COMPL-SI); 2) to separately analyse the interference of COMs and COMPLs with functional status and recovery during stroke rehabilitation treatment; 3) to compare the ability of COM-SI and COMPL-SI to predict functional independence at discharge with that of w-CI. METHODS: Eighty-five stroke rehabilitation inpatients participated in the study. The type, incidence and severity of COM at admission and of COMPL during the whole hospital stay were studied prospectively. The Functional Independence Measure (FIM) scale was administered at both admission and discharge. RESULTS: About 1/3 suffered from some significant COM and another 1/3 developed COMPLs needing specific medical treatment and/or clinical monitoring. The most frequent COMs and COMPLs were cardiovascular and psychiatric/psychological diseases. The odds of having a high efficiency in the daily functional gain (FIM score) were greater for patients without any COM (3.5) and/or COMPL (4.6). Similarly, the odds of having a high FIM score at discharge were greater (3.5) for patients without COM or COMPL. The COM-SI demonstrated a higher predictive capacity of the FIM score at discharge (5%) than w-CI (4%), and COMPL-SI (1%). CONCLUSIONS: COM-SI resulted as the most interesting predictive index of functional outcome at discharge, after accounting for the functional status at admission.

PMID: 16767056 [PubMed - in process]

Cardiovascular responses to static exercise in boys: insights from tissue Doppler imaging.

Sunday, June 18th, 2006
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Cardiovascular responses to static exercise in boys: insights from tissue Doppler imaging.

Eur J Appl Physiol. 2006 Jun 13;

Authors: Rowland T, Heffernan K, Jae SY, Echols G, Krull G, Fernhall B

Ventricular functional changes and mechanisms of the cardiovascular responses during static exercise have not been well delineated in children. In this study, Doppler echocardiographic techniques were utilized to assess cardiovascular adaptations to bilateral isometric leg extension at 30% maximal voluntary contraction for three minutes in a group of 14 healthy boys (mean age 10.2 +/- 1.5 years). Mean heart rate rose from 77 +/- 9 to 106 +/- 11 bpm, stroke volume fell from 59 +/- 9 to 52 +/- 7 ml, and cardiac output increased from 4.58 +/- 0.58 to 5.62 +/- 0.81 l min(-1) (P < 0.05). Mean arterial pressure rose from 86 +/- 7 to 109 +/- 9 mm Hg, with no significant change in peripheral vascular resistance. By tissue Doppler imaging markers, inotropic function improved by 59%, while lusitropic function increased 38%. These findings suggest that (1) cardiovascular responses to static leg extension in boys are similar to those in adult men, and (2) isometric leg extension triggers modest increases in both systolic and diastolic function.

PMID: 16770566 [PubMed - as supplied by publisher]

Endothelial dysfunction in MELAS improved by l-arginine supplementation.

Sunday, June 18th, 2006
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Endothelial dysfunction in MELAS improved by l-arginine supplementation.

Neurology. 2006 Jun 13;66(11):1766-9

Authors: Koga Y, Akita Y, Junko N, Yatsuga S, Povalko N, Fukiyama R, Ishii M, Matsuishi T

The authors evaluated endothelial function in patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke) by flow-mediated vasodilation (FMD) and found a significant decrease vs controls. Two years of supplementation with oral l-arginine, a nitric oxide precursor, significantly improved endothelial function to control levels and was harmonized with the normalized plasma levels of l-arginine in patients. l-Arginine therapy improved endothelial dysfunction and showed promise in treating strokelike episodes in MELAS.

PMID: 16769961 [PubMed - in process]

Influence of gender on outcomes after intra-arterial thrombolysis for acute ischemic stroke.

Sunday, June 18th, 2006
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Influence of gender on outcomes after intra-arterial thrombolysis for acute ischemic stroke.

Neurology. 2006 Jun 13;66(11):1745-6

Authors: Shah SH, Liebeskind DS, Saver JL, Starkman S, Vinuela F, Duckwiler G, Jahan R, Kim D, Sanossian N, Vespa P, Ovbiagele B

Recent data suggest that women obtain greater benefit than men from IV fibrinolysis for acute ischemic stroke. It is unknown whether this gender-thrombolysis advantage extends to those treated with intra-arterial (IA) thrombolysis. The authors evaluated the independent effect of gender among ischemic stroke patients treated with IA fibrinolysis and found no differences in short-term clinical and angiographic outcomes between men and women who received IA thrombolysis for acute ischemic stroke.

PMID: 16769954 [PubMed - in process]

Mortality of stroke patients treated with thrombolysis: analysis of nationwide inpatient sample.

Sunday, June 18th, 2006
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Mortality of stroke patients treated with thrombolysis: analysis of nationwide inpatient sample.

Neurology. 2006 Jun 13;66(11):1742-4

Authors: Dubinsky R, Lai SM

The authors performed a retrospective cohort comparison using the Nationwide Inpatient Sample for 1999 through 2002 of acute ischemic stroke admissions. Mortality was compared based on the use of thrombolysis. Hospital mortality was significantly greater for the thrombolysis cohort (10.1% vs 5.8%) as was the rate of secondary intracranial hemorrhage (4.2% vs 0.4%). US community experience in the use of thrombolysis has higher rates of complications and mortality than in controlled clinical trials.

PMID: 16769953 [PubMed - in process]

Ischemic strokes after cardiac catheterization: opportune thrombolysis candidates?

Sunday, June 18th, 2006
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Ischemic strokes after cardiac catheterization: opportune thrombolysis candidates?

Arch Neurol. 2006 Jun;63(6):817-21

Authors: Khatri P, Kasner SE

Stroke is an important complication after cardiac catheterization procedures, resulting in death and disability for thousands of patients each year. Common risk factors include advanced age, vascular comorbidities, and more complicated and invasive procedures. Several lines of evidence suggest that these strokes are embolic, from either dislodgement of a clot or atheromatous debris off the aortic arch or from thrombus formation on the tip of a guide catheter. These strokes are likely amenable to thrombolysis, although the current literature regarding the use of thrombolysis in this setting is limited to case reports and series. Whether thrombolysis is safe and efficacious remains to be determined, but the existing evidence seems favorable for individual circumstances.

PMID: 16769862 [PubMed - in process]

The Cellular Basis for Enhanced Volume-modulated Cardiac Output in Fish Hearts.

Sunday, June 18th, 2006
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The Cellular Basis for Enhanced Volume-modulated Cardiac Output in Fish Hearts.

J Gen Physiol. 2006 Jun 12;

Authors: Shiels HA, Calaghan SC, White E

During vertebrate evolution there has been a shift in the way in which the heart varies cardiac output (the product of heart rate and stroke volume). While mammals, birds, and amphibians increase cardiac output through large increases in heart rate and only modest increases ( approximately 30%) in stroke volume, fish and some reptiles use modest increases in heart rate and very large increases in stroke volume (up to 300%). The cellular mechanisms underlying these fundamentally different approaches to cardiac output modulation are unknown. We hypothesized that the divergence between volume modulation and frequency modulation lies in the response of different vertebrate myocardium to stretch. We tested this by progressively stretching individual cardiac myocytes from the fish heart while measuring sarcomere length (SL), developed tension, and intracellular Ca(2+) ([Ca(2+)](i)) transients. We show that in fish cardiac myocytes, active tension increases at SLs greater than those previously demonstrated for intact mammalian myocytes, representing a twofold increase in the functional ascending limb of the length-tension relationship. The mechanism of action is a length-dependent increase in myofilament Ca(2+) sensitivity, rather than changes in the [Ca(2+)](i) transient or actin filament length in the fish cell. The capacity for greater sarcomere extension in fish myocardium may be linked to the low resting tension that is developed during stretch. These adaptations allow the fish heart to volume modulate and thus underpin the fundamental difference between the way fish and higher vertebrates vary cardiac output.

PMID: 16769795 [PubMed - as supplied by publisher]

Oral contraceptive use, thrombophilia and their interaction in young women with ischemic stroke.

Sunday, June 18th, 2006
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Oral contraceptive use, thrombophilia and their interaction in young women with ischemic stroke.

Haematologica. 2006 Jun;91(6):844-7

Authors: Martinelli I, Battaglioli T, Burgo I, Di Domenico S, Mannucci PM

To investigate the role of oral contraceptives and their interaction with thrombophilia in ischemic stroke, a case-control study on women with a first ischemic stroke when younger than 45 years was carried out. Oral contraceptives doubled the risk of ischemic stroke in the first 6-18 months of use and hyperhomocysteinemia increased the risk by 3.5-fold. Carriers of factor V Leiden or prothrombin G20210A were not found to have a statistically significant increased risk. The risk of ischemic stroke in oral contraceptive users was 13 times higher in women who were also carriers of factor V Leiden and 9 times higher in those who also had hyperhomocysteinemia.

PMID: 16769590 [PubMed - in process]

Neurologic complications of lymphoma and leukemia.

Sunday, June 18th, 2006
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Neurologic complications of lymphoma and leukemia.

Semin Oncol. 2006 Jun;33(3):342-7

Authors: Glass J

Lymphoma and leukemia are systemic diseases that affect many end-organs, including the central nervous system. These cancers may directly affect the central or peripheral nervous systems by the production of intraparenchymal or extra-axial mass lesions or by meningeal infiltration. Vascular occlusion may occur as a result of blockage of blood vessels by tumor cells. A variety of paraneoplastic syndromes occur and are most commonly associated with plasma cell tumors. Coagulopathy and metabolic disturbances are direct and indirect effects of these cancers and also are associated with their treatment, resulting in disturbances of consciousness, intracranial hemorrhage, or ischemic stroke. The agents used in the treatment of lymphoma and leukemia are also associated with neurological toxicity. This chapter reviews these neurological manifestations of lymphoma and leukemia and their therapies.

PMID: 16769423 [PubMed - in process]

The challenges of new drugs benefits and risks analysis: Lessons from the ximelagatran FDA Cardiovascular Advisory Committee.

Sunday, June 18th, 2006
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The challenges of new drugs benefits and risks analysis: Lessons from the ximelagatran FDA Cardiovascular Advisory Committee.

Contemp Clin Trials. 2006 May 6;

Authors: Boudes PF

Ximelagatran is a new oral anticoagulant that acts by direct and reversible inhibition of thrombin and has the potential to replace warfarin. In 2004, the FDA Cardiovascular and Renal drug Advisory Committee (CRAC) reviewed the ximelagatran clinical program. Three indications were proposed: the prevention of venous thromboembolism (VTE) in patients undergoing total knee replacement surgery (TKR), the prevention of stroke and other thromboembolic complications associated with atrial fibrillation (AF), and the long-term secondary prevention of VTE after standard treatment of an episode of acute VTE. The database consisted of a total of 30,698 subjects and included five phase III pivotal studies. During the advisory panel debate, widely divergent analyses of the benefits and risks of ximelagatran were presented. Ximelagatran hepatic toxicity was a key feature leading the CRAC to conclude that the benefit risk ratio of ximelagtran was unfavorable for the three proposed indications. Some design issues also undermined the strength of efficacy data. This paper reviews the benefits and risks of ximelagatran and analyzes the reasons leading to conflicting conclusions among various experts. The aim of this review is to facilitate the interpretation of benefits and risks associated with a new drug product and to improve future clinical drug developments.

PMID: 16769255 [PubMed - as supplied by publisher]

Human epilepsies: interaction of genetic and acquired factors.

Sunday, June 18th, 2006
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Human epilepsies: interaction of genetic and acquired factors.

Trends Neurosci. 2006 Jun 10;

Authors: Berkovic SF, Mulley JC, Scheffer IE, Petrou S

Epilepsies, once regarded as due to demoniacal possession, can have both genetic and acquired causes, with interaction of these factors in many cases. To date, nearly all the genes discovered to be involved in human epilepsies encode subunits of ion channels, both voltage-gated and ligand-gated. Established acquired causes include serious brain trauma, stroke, tumours and infective lesions. Thus, in terms of exploring the neurobiology of ‘nature and nurture’ in disease, the epilepsies are an excellent paradigm. Here, we review the evidence and discuss the possibility that ion channels are a common biological substrate for both genetic and acquired epilepsies. This review is part of the INMED/TINS special issue Nature and nurture in brain development and neurological disorders, based on presentations at the annual INMED/TINS symposium ().

PMID: 16769131 [PubMed - as supplied by publisher]

Visual neglect following right posterior cerebral artery infarction.

Sunday, June 18th, 2006
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Visual neglect following right posterior cerebral artery infarction.

J Neurol Neurosurg Psychiatry. 2006 Jun 14;

Authors: Bird CM, Malhotra P, Parton A, Coulthard E, Rushworth MF, Husain M

OBJECTIVES: To investigate the characteristics and neuroanatomical correlates of visual neglect following right-sided posterior cerebral artery (PCA) infarction. METHODS: 15 patients with acute PCA strokes were screened for the presence of neglect on a comprehensive battery of cognitive tests. 6 patients were also administered extra tests of visual perception. To establish what areas were critically involved in neglect, we directly contrasted the lesions of patients with and without neglect. RESULTS: Neglect of varying severity was documented in 8 patients. In addition, higher-order visual perception was impaired in 5 of the 6 patients. Neglect was critically associated with damage to an area of white matter in the occipital lobe corresponding to a white matter tract connecting the parahippocampal gyrus with the angular gyrus of the parietal lobe. Lesions of the thalamus or splenium of the corpus callosum did not appear necessary or sufficient to cause neglect, but may mediate its severity in these patients. CONCLUSIONS: PCA stroke can result in visual neglect. Our results suggest that interruption of the white matter fibres connecting the parahippocampal gyrus to the angular gyrus may be important in determining whether a patient will manifest neglect.

PMID: 16772354 [PubMed - as supplied by publisher]

Kv1.5 channelopathy due to KCNA5 loss-of-function mutation causes human atrial fibrillation.

Sunday, June 18th, 2006
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Kv1.5 channelopathy due to KCNA5 loss-of-function mutation causes human atrial fibrillation.

Hum Mol Genet. 2006 Jun 13;

Authors: Olson TM, Alekseev AE, Liu XK, Park S, Zingman LV, Bienengraeber M, Sattiraju S, Ballew JD, Jahangir A, Terzic A

Atrial fibrillation is a rhythm disorder characterized by chaotic electrical activity of cardiac atria. A precipitant of stroke and heart failure, this common condition is increasingly recognized as a heritable disorder. To identify genetic defects conferring disease susceptibility, patients with idiopathic atrial fibrillation, lacking traditional risk factors, were evaluated. Genomic DNA scanning revealed a nonsense mutation in KCNA5 that encodes Kv1.5, a voltage-gated potassium channel expressed in human atria. The heterozygous E375X mutation, present in a familial case of atrial fibrillation and absent in 540 unrelated control individuals, introduced a premature stop codon disrupting the Kv1.5 channel protein. The truncation eliminated the S4-S6 voltage-sensor and pore region/C-terminus, preserving the N-terminus and S1-S3 transmembrane domains that secure tetrameric subunit assembly. Heterologously expressed recombinant E375X mutant failed to generate the ultrarapid delayed rectifier current IKur vital for atrial repolarization, and exerted a dominant-negative effect on wildtype current. Loss of channel function translated into action potential prolongation and early after-depolarization in human atrium, increasing vulnerability to stress-provoked triggered activity. The pathogenic link between compromised Kv1.5 function and susceptibility to atrial fibrillation was verified, at the organism level, in a murine model. Rescue of the genetic defect was achieved by aminoglycoside-induced translational read-through of the E375X premature stop codon restoring channel function. This first report of Kv1.5 loss-of-function channelopathy establishes KCNA5 mutation as a novel risk factor for repolarization deficiency and atrial fibrillation.

PMID: 16772329 [PubMed - as supplied by publisher]

Early Carotid Endarterectomy after Ischemic Stroke: The Results of a Prospective Multicenter Italian Study.

Sunday, June 18th, 2006
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Early Carotid Endarterectomy after Ischemic Stroke: The Results of a Prospective Multicenter Italian Study.

Eur J Vasc Endovasc Surg. 2006 Jun 10;

Authors: Sbarigia E, Toni D, Speziale F, Acconcia C, Fiorani P

OBJECTIVES: To evaluate safety of early carotid endarterectomy (CEA) in patients with acute brain ischemia presenting to the emergency department stroke units (EDSU). METHODS: The neurologists, neuroradiologists and vascular surgeons on duty in emergency departments enrolled 96 patients who underwent very early CEA according to a predefined protocol within two years. The protocol included evaluation of neurological status by National Institute of Health Stroke Scale (NIHSS), neuroimaging assessment, ultrasound of the carotid arteries and Transcranial Doppler. Patients with NIHSS>22 or whose neuroimaging showed brain infarct >2/3 of the middle cerebral artery territory were excluded. All eligible patients underwent CEA as soon as possible. Primary end points of the study were mortality, neurological morbidity by NIHSS and postoperative hemorrhagic conversion on neuroimaging. Statistical analysis was performed by univariate analysis. RESULTS: The mean time elapsing between the onset of stroke and endarterectomy was 1.5 days (+/-2 days). The overall 30-day morbidity mortality rate was 7.3% (7/96). No neurological mortality occurred. On hospital discharge, three patients (3%) experienced worsening of the neurological deficit (NIHSS score 1 to 2, 1 to 3 and 9 to 10 respectively). Postoperative CT demonstrated there were no new cerebral infarcts nor hemorrhagic transformation. At hospital discharge 9/96 patients (9%) had no improvement in NHISS scores, 37 were asymptomatic and 45 showed a median decrease of 4.5 NIHSS points (range 1-18). By univariate analysis none of the considered variables influenced the clinical outcome. CONCLUSION: Our protocol selected patients who can safely undergo very early (<1.5 days) surgery after acute brain ischemia. Large randomized multicenter prospective trials are warranted to compare very early CEA versus best medical therapy.

PMID: 16772113 [PubMed - as supplied by publisher]

“This case is closed”: family caregivers and the termination of home health care services for stroke patients.

Sunday, June 18th, 2006
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“This case is closed”: family caregivers and the termination of home health care services for stroke patients.

Milbank Q. 2006;84(2):305-31

Authors: Levine C, Albert SM, Hokenstad A, Halper DE, Hart AY, Gould DA

Policies promoting home- and community-based services and disease management models implicitly rely on family care, still the bedrock of long-term and chronic care in the United States. The United Hospital Fund studied family caregivers of stroke and brain injury patients when home care cases were opened and closed and found that even with short-term formal services, family caregivers provided three-quarters of the care. Patients’ mobility impairments and Medicaid eligibility were the main factors in determining the amount and duration of formal services. Between one-third and one-half of family caregivers reported being inadequately prepared for the case closing. At all stages, family caregivers expressed significant isolation, anxiety, and depression. Therefore, home care agency practice and public policies should provide better education, support, and services for family caregivers.

PMID: 16771820 [PubMed - in process]

Team-based approach reduces learning curve in robot-assisted laparoscopic radical prostatectomy.

Sunday, June 18th, 2006
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Team-based approach reduces learning curve in robot-assisted laparoscopic radical prostatectomy.

Int J Urol. 2006 May;13(5):560-4

Authors: Sim HG, Yip SK, Lau WK, Tan YH, Wong MY, Cheng CW

Aim: We assessed the team approach in reducing the learning curve during our 2-year experience transiting from open to robot-assisted laparoscopic radical prostatectomy (rLRP). Methods: A team of three urologists progressed through assistant phase to console phase to obtain competency in robotic prostatectomy. One hundred patients underwent rLRP by this team using the da Vinci robotic surgical system from 1 February 2003 to 15 May 2005. Results: The immediate perioperative outcome was divided into three corresponding time frames and the results demonstrated gradual improvement in outcome parameters. The mean set-up time and dissection time were 24 +/- 14 min and 182 +/- 52 min, respectively. The mean perioperative blood loss was 272 +/- 240 mL, and 7% of patients (n = 7) required blood transfusion. The mean duration of bladder catheterization was 8.4 +/- 4.1 days, and mean hospital stay was 2.9 +/- 1.6 days. There was no perioperative mortality or conversion to open radical prostatectomy. Major complications (4%) included urethrovesical leak requiring re-operation, postoperative cerebrovascular accident, and transient ureteric obstruction. Minor complications (7%) included minor urethrovesical leak, bladder neck stenosis, and urinary tract infection. Mean follow up was 6.6 +/- 5.0 months. Pathological assessment showed pT2 disease in 55% and pT3 in 45% of specimens. Conclusions: A team-based approach to robot-assisted LRP helped to reduce the learning curve of the procedure for individual surgeons and continued to show significantly lower perioperative blood loss, transfusion requirements and postoperative pain compared to open radical retropubic prostatectomy.

PMID: 16771713 [PubMed - in process]

Postprandial levels of the natural vitamin e tocotrienol in human circulation.

Sunday, June 18th, 2006
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Postprandial levels of the natural vitamin e tocotrienol in human circulation.

Antioxid Redox Signal. 2006 May-Jun;8(5-6):1059-68

Authors: Khosla P, Patel V, Whinter JM, Khanna S, Rakhkovskaya M, Roy S, Sen CK

Compared to tocopherols, tocotrienols are poorly understood. The postabsorptive fate of tocotrienol isomers and their association with lipoprotein subfractions was examined. Normocholesterolemic women were subjected to an oral fat challenge supplemented with vitamin E (capsule containing 77 mg alpha-tocotrienol, 96 mg alpha-tocotrienol, 3 mg gamma-tocotrienol, 62 mg alpha-tocopherol, and 96 mg gamma-tocopherol). Plasma samples were collected at every 2 h intervals for up to 8 h following a one-time supplementation. Lipoproteins were measured by NMR spectroscopy, and subfractions of lipoproteins were isolated by density gradient ultracentrifugation. The maximal alpha-tocotrienol concentrations in supplemented individuals averaged approximately 3 microM in blood plasma, 1.7 microM in LDL, 0.9 microM in triglyceride-rich lipoprotein, and 0.5 microM in HDL. The peak plasma level corresponded to 12- to 30-fold more than the concentration of alpha-tocotrienol required to completely prevent stroke-related neurodegeneration. Tocotrienols were detected in the blood plasma and all lipoprotein subfractions studied postprandially.

PMID: 16771695 [PubMed - in process]

Decreased expression of brain-derived neurotrophic factor in BDNF(+/-) mice is associated with enhanced recovery of motor performance and increased neuroblast number following experimental stroke.

Sunday, June 18th, 2006
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Decreased expression of brain-derived neurotrophic factor in BDNF(+/-) mice is associated with enhanced recovery of motor performance and increased neuroblast number following experimental stroke.

J Neurosci Res. 2006 Jun 12;

Authors: Nygren J, Kokaia M, Wieloch T

Brain-derived neurotrophic factor (BDNF) is involved in brain plasticity and neuronal survival. Generally, BDNF enhances synaptic activity and neurite growth, although the effect of BDNF on neuronal survival and brain plasticity following injury is equivocal. Housing rats in an enriched environment after experimental stroke enhances recovery of sensory-motor function, which is associated with a decrease in the BDNF mRNA and protein levels. We used BDNF(+/-) mice and wild-type littermate mice to investigate whether the decrease in the brain levels of BDNF affected motor function or infarct volume following transient occlusion of the middle cerebral artery (tMCAO) for 40 min. We found that the BDNF(+/-) mice had a significantly improved motor function on the rotating pole test 2 weeks after tMCAO compared with wild-type mice. When intermittently exposed to an enriched environment following tMCAO, the wild-type mice improved motor function to the same degree as BDNF(+/-) mice. There was no effect of BDNF reduction on infarct volume. Neurogenesis is induced following experimental stroke, and in the striatum of BDNF(+/-) mice significantly increased numbers of neuroblasts compared with wild-type mice were seen, both in standard and in enriched conditions. We conclude that decreasing brain levels of BDNF enhances the recovery of function following experimental stroke. (c) 2006 Wiley-Liss, Inc.

PMID: 16770774 [PubMed - as supplied by publisher]

Sonographic templates of newborn perforator stroke.

Sunday, June 18th, 2006
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Sonographic templates of newborn perforator stroke.

Pediatr Radiol. 2006 Jul;36(7):663-669

Authors: Abels L, Lequin M, Govaert P

BACKGROUND: Many paediatric strokes occur in the perinatal period. Improvement in neuroimaging has increased detection in newborns with neurological symptoms. OBJECTIVE: To define sonographic templates of neonatal stroke in the territory of perforators of the anterior choroidal artery (AChA) and the anterior (ACA), middle (MCA) and posterior (PCA) cerebral arteries. MATERIALS AND METHODS: In 24 neonates with perforator stroke, we retrospectively studied antenatal and perinatal events. Brain sonography was performed with an 8.5-MHz probe. Only hyperechoic lesions in the thalamus and/or striatum and/or centrum semiovale were included. MRI was obtained using a 1.5-T machine. RESULTS: We detected 28 perforator strokes in 24 infants (6 preterm): 5 MCA medial striate, 8 MCA lateral striate, 3 MCA centrum semiovale, 4 ACA Heubner’s, 5 PCA thalamic arteries, 1 AChA, and 2 hypothalamic perforators. We attributed clinical seizures to stroke in two infants only. Catheter-related embolism (certain in three, possible in six others) and birth trauma (two) were probable causes. Specific conditions were found in six others. Only one infant (in nine evaluated) had an increased prothrombotic risk (fII mutation). In describing the lesions, we focused on the templates of infarction as seen in a parasagittal US sweep. Infarcts were confirmed by MRI in 21 patients. CONCLUSION: Our study showed that infarct topography can be evaluated reliably with brain sonography. This is important given the asymptomatic character of most lesions.

PMID: 16770669 [PubMed - as supplied by publisher]

Toward a Further Elucidation: Role of Vertebral Artery Hypoplasia in Acute Ischemic Stroke.

Sunday, June 18th, 2006
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Toward a Further Elucidation: Role of Vertebral Artery Hypoplasia in Acute Ischemic Stroke.

Eur Neurol. 2006 Jun 13;55(4):193-197

Authors: Chuang YM, Huang YC, Hu HH, Yang CY

Background and Purpose: Congenital vertebral artery (VA) hypoplasia is an uncommon embryonic variation of posterior circulation. The frequency of this congenital variation was reported to be 2-6% from autopsy and angiograms. The aim of our study was to elucidate the role of VA hypoplasia in acute ischemic stroke. Method: We examined 191 acute ischemic stroke patients (age 55.8 +/- 14.0 years). TOAST subtypes were determined. A cervical magnetic resonance angiogram was performed in every patient. A duplex study of bilateral VA with flow velocities and vessel diameter recording in the intertransverse (V2) segment was performed within 72 h after onset of ischemic stroke. The net VA flow volume was measured in each subject. Result: The overall incidence of a unilateral congenital hypoplastic VA was 11.51%, which was statistically higher especially in cases of brainstem/cerebellar infarction. Of these, subjects with VA hypoplasia had an etiological preponderance of the ‘large-artery atherosclerosis’ subtype and a topographic preponderance of ipsilateral posterior circulation infarction. Conclusions: Based on our results, VA hypoplasia seemed a contributing factor of acute ischemic stroke, especially in posterior circulation territories. Copyright (c) 2006 S. Karger AG, Basel.

PMID: 16772715 [PubMed - as supplied by publisher]

EEG Findings after a Cerebral Territorial Infarct in Patients Who Develop Early- and Late-Onset Seizures.

Sunday, June 18th, 2006
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EEG Findings after a Cerebral Territorial Infarct in Patients Who Develop Early- and Late-Onset Seizures.

Eur Neurol. 2006 Jun 13;55(4):209-213

Authors: De Reuck J, Goethals M, Claeys I, Van Maele G, De Clerck M

Background: EEG findings are generally not considered to be very helpful for the diagnosis of poststroke seizures. Purpose: This retrospective study investigates the EEG characteristics in patients who develop seizures after a cerebral territorial infarct. Patients and Methods: The study population consisted of 110 patients with seizures after a cerebral territorial infarct (12 with early- and 98 with late-onset seizures) and 275 without. All 110 patients had an interictal EEG after their first seizure. The EEG patterns after the stroke were compared between those available from 69 patients who developed seizures and those from 275 who did not. Also the EEG patterns after the seizure (n = 110) were compared to those in the poststroke group without subsequent seizures. Results: Periodic lateralized epileptic discharges (PLEDs) on the EEG after stroke were only found in 5.8% of the patients with early- and late-onset seizures. They were absent in the stroke group without seizures. Frontal intermittent rhythmic delta activities (FIRDAs) were observed in 24.6% of the seizure group, compared to 1.1% in the control group. Diffuse slowing occurred also significantly more often in the former (21.7%) compared to the latter group (5.1%). Normal EEG findings were seen in 53.8% of the stroke patients without seizures, compared to 8.5% in those with seizures. The incidence of focal slowing was the same in both groups. Similar findings were observed when comparing the EEG patterns of the patients after the first poststroke seizure to those of the stroke group without subsequent seizures. In patients with early-onset seizures, PLEDs or FIRDAs were present in 25% each. FIRDAs and diffuse slowing were significantly more frequently observed on the poststroke EEGs of patients who developed late-onset seizures. Conclusions: FIRDAs, PLEDs and diffuse slowing are the most frequent EEG findings in patients with early-onset seizures. Patients with FIRDAs and diffuse slowing on the poststroke EEG have a high risk to develop late-onset seizures, while the chance is reduced in those with normal EEG findings. Copyright (c) 2006 S. Karger AG, Basel.

PMID: 16772712 [PubMed - as supplied by publisher]

Modulation of thrombin-induced neuroinflammation in BV-2 microglia by a carbon monoxide-releasing molecule (CORM-3).

Sunday, June 18th, 2006
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Modulation of thrombin-induced neuroinflammation in BV-2 microglia by a carbon monoxide-releasing molecule (CORM-3).

J Pharmacol Exp Ther. 2006 Jun 13;

Authors: Bani-Hani MG, Greenstein D, Mann BE, Green CJ, Motterlini R

Carbon monoxide-releasing molecules (CO-RMs) are emerging as a new class of pharmacological agents that regulate important cellular function by liberating CO in biological systems. Here, we examined the role of CORM-3 in modulating neuro-inflammatory responses in BV-2 microglial cells, considering its practical application as a novel therapeutic alternative in the treatment of stroke. BV-2 microglia cells were incubated for 24 h in normoxic conditions with thrombin alone or in combination with interferon-gamma to simulate the inflammatory response. Cells were also subjected to 12 h hypoxia and reoxygenated for 24 h in the presence of thrombin and IFN-gamma. In both set of experiments, the anti-inflammatory action of CORM-3 was evaluated by assessing its effect on nitric oxide production (nitrite levels) and TNF-alpha release. CORM-3 (75 microM) did not show any cytotoxicity and markedly attenuated the inflammatory response to thrombin and interferon-gamma in normoxia and to a lesser extent in hypoxia as evidenced by a significant reduction in nitrite and TNF-alpha production. Inactive CORM-3, which does not liberate CO and is used as a negative control, failed to prevent the increase in inflammatory mediators. Blockade of endogenous CO production by tin protoporphyrin-IX did not change the anti-inflammatory activity of CORM-3 suggesting that CO liberated from the compound is responsible for the observed effects. In addition, inhibition of the mitogen-activated protein kinases PI3K and ERK amplified the anti-inflammatory effect of CORM-3. These results suggest that the anti-inflammatory activity of CORM-3 could be exploited to mitigate microglia activity in stroke and other neuro-inflammatory diseases.

PMID: 16772536 [PubMed - as supplied by publisher]

Sleep disordered breathing after stroke. A randomized controlled trial of continuous positive airway pressure.

Sunday, June 18th, 2006
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Sleep disordered breathing after stroke. A randomized controlled trial of continuous positive airway pressure.

J Neurol Neurosurg Psychiatry. 2006 Jun 13;

Authors: Hsu CY, Vennelle M, Li HY, Engleman HM, Dennis MS, Douglas NJ

BACKGROUND: Sleep disordered breathing (SDB) is common after stroke but it is unclear whether it should be treated. OBJECTIVE: We performed a randomized controlled trial of continuous positive airways pressure (CPAP) following stroke. METHODS: Stroke patients with >/= 30 apnoeas and hypopnoeas per hour [(A+H).h-1] with predominant obstructive sleep apnoea or hypopnoea were randomized to either CPAP treatment or conservative treatment for 8 weeks. Outcomes were measured blind to treatment allocation at 8 weeks and 6 months after the stroke. The primary outcome was physical function on the Nottingham Extended Activities of Daily Living Scale. RESULTS: Of 658 stroke patients screened, only 71 (10.7%) were eligible and consented to a sleep study 14-19 days post stroke. Sixty-six patients completed the sleep study (21 women; mean age 72 years), 33 (50%) had >/= 30 (A+H).h-1 which were predominantly obstructive. Fifteen were randomized to CPAP and 15 to conventional treatment. Despite intensive efforts, objective use of CPAP was poor, averaging 1.4 hours per night. CPAP resulted in no significant improvements in the primary outcome or in neurological function or sleepiness and in poorer health status on some measures. CONCLUSIONS: This trial showed no benefit from CPAP treatment, the significance of the observed detrimental effects is questionable. Even in our highly selected stroke patients, use of CPAP was poor. At present CPAP treatment should be advocated for stroke patients only if they have symptoms of SDB.

PMID: 16772358 [PubMed - as supplied by publisher]

An evaluation of a multidisciplinary team for intermediate care at home.

Sunday, June 18th, 2006
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An evaluation of a multidisciplinary team for intermediate care at home.

Int J Integr Care. 2004;4:e02

Authors: Beech R, Russell W, Little R, Sherlow-Jones S

BACKGROUND: The implementation of the National Health Service Plan for the UK will see an expansion of services for intermediate care. Such services are usually targeted at older people and aim to: prevent ‘avoidable’ admissions to acute inpatient care; facilitate the timely discharge of patients from acute inpatient care; promote patient rehabilitation. A range of services might fall under the banner of intermediate care. They are usually delivered in patients’ homes or in non-acute institutions. This paper describes an evaluation of a multidisciplinary Rapid Response Team (RRT). This service aimed to provide a home based alternative to care previously provided in an acute hospital bed which was acceptable to patients and carers and which maintained clinical care standards. The service was provided for the population of Hereford, a rural town in the middle of England. METHODS: A mixed-method descriptive design using quantitative and qualitative techniques was used to monitor: the characteristics of service users, the types and amounts of care received, any ‘adverse’ events arising from that care, and the acceptability of the service to patients and carers. A collaborative approach involving key stakeholders allowed appropriate data to be gathered from patient case notes, RRT staff, local health and social care providers, and patients and their carers. A suite of self-completed questionnaires was, therefore, designed to capture study data on patients and activities of care, and workshops and semi-structured interview schedules used to obtain feedback from users and stakeholders. RESULTS: Service users (231) were elderly (mean age 75.9), from three main diagnostic categories (respiratory conditions 19.0%, heart/stroke 16.2%, falls 13.4%), with the majority (57.0%) having both medical and social care needs. All patients received care at home (mean duration 5.6 days) with only 5.7% of patients having to be re-admitted to acute care. Overall, patients and carers had positive attitudes to the new service but some expressed concerns about their ability to influence the choice of care option (24.1% and 25.0% of patients and carers, respectively), whilst 22.7% of carers were concerned about the quality of information about care. CONCLUSIONS: Both the nature of schemes for intermediate care, and the policy context in which they are introduced, mean that pragmatic methodologies are often required to evaluate their impacts. Unfortunately, this need for pragmatism can then mean that it is difficult to reach definitive conclusions about the merits of schemes. However, the findings of this evaluation suggest that the Rapid Response Team provided an ‘acceptable’ alternative to an extended period of care in an acute setting. Such schemes may have relevance beyond the NHS of the UK as a means of providing a more appropriate and cost efficient match between patients’ needs for care, the types of care provided, and the place in which care is provided.

PMID: 16773151 [PubMed - in process]

Improved reperfusion and neuroprotection by creatine in a mouse model of stroke.

Sunday, June 18th, 2006
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Improved reperfusion and neuroprotection by creat