Isolation of Primary Human Hepatocytes from Normal and Diseased Liver Tissue: A One Hundred Liver Experience

Successful and consistent isolation of primary human hepatocytes remains a challenge for both cell-based therapeutics/transplantation and laboratory research. Several centres around the world have extensive experience in the isolation of human hepatocytes from non-diseased livers obtained from donor liver surplus to surgical requirement or at hepatic resection for tumours. These livers are an important but limited source of cells for therapy or research. The capacity to isolate cells from diseased liver tissue removed at transplantation would substantially increase availability of cells for research. However no studies comparing the outcome of human hepatocytes isolation from diseased and non-diseased livers presently exist. Here we report our experience isolating human hepatocytes from organ donors, non-diseased resected liver and cirrhotic tissue. We report the cell yields and functional qualities of cells isolated from the different types of liver and demonstrate that a single rigorous protocol allows the routine harvest of good quality primary hepatocytes from the most commonly accessible human liver tissue samples

Automated versus manual post-processing of perfusion-CT data in patients with acute cerebral ischemia: influence on interobserver variability

The purpose of this study is to compare the variability of PCT results obtained by automatic selection of the arterial input function (AIF), venous output function (VOF) and symmetry axis versus manual selection. Imaging data from 30 PCT studies obtained as part of standard clinical stroke care at our institution in patients with suspected acute hemispheric ischemic stroke were retrospectively reviewed. Two observers performed the post-processing of 30 CTP datasets. Each observer processed the data twice, the first time employing manual selection of AIF, VOF and symmetry axis, and a second time using automated selection of these same parameters, with the user being allowed to adjust them whenever deemed appropriate. The volumes of infarct core and of total perfusion defect were recorded. The cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT) and blood-brain barrier permeability (BBBP) values in standardized regions of interest were recorded. Interobserver variability was quantified using the Bland and Altman's approach. Automated post-processing yielded lower coefficients of variation for the volume of the infarct core and the volume of the total perfusion defect (15.7% and 5.8%, respectively) compared to manual post-processing (31.0% and 12.2%, respectively). Automated post-processing yielded lower coefficients of variation for PCT values (11.3% for CBV, 9.7% for CBF, and 9.5% for MTT) compared to manual post-processing (23.7% for CBV, 32.8% for CBF, and 16.7% for MTT). Automated post-processing of PCT data improves interobserver agreement in measurements of CBV, CBF and MTT, as well as volume of infarct core and penumbra

Guidelines for management of ischaemic stroke and transient ischaemic attack 2008

This article represents the update of the European Stroke Initiative Recommendations for Stroke Management. These guidelines cover both ischaemic stroke and transient ischaemic attacks, which are now considered to be a single entity. The article covers referral and emergency management, Stroke Unit service, diagnostics, primary and secondary prevention, general stroke treatment, specific treatment including acute management, management of complications, and rehabilitation

An observational study of bimatoprost 0.01% in treatment-naïve patients with primary open angle glaucoma or ocular hypertension: the CLEAR trial

Donald R Nixon,1 Susan Simonyi,2 Meetu Bhogal,2 Christopher S Sigouin,3 Andrew C Crichton,4 Marino Discepola,5 Cindy ML Hutnik,6 David B Yan71Private Practice, Barrie, ON, 2Allergan Inc, Markham, ON, 3CLINWest Research, Burlington, ON, 4University of Calgary, Calgary, AB, 5McGill University, Montreal, QC, 6London Health Sciences Centre, London, ON, 7University of Toronto, Toronto, ON, CanadaBackground: This study was designed to evaluate the occurrence and severity of ocular hyperemia in subjects with elevated intraocular pressure (IOP) due to primary open angle glaucoma (POAG) or ocular hypertension (OHT) following treatment with bimatoprost 0.01% in a real-world clinical setting.Methods: This was an open-label, observational study conducted at 67 centers in Canada. Subjects with elevated IOP due to POAG or OHT instilled bimatoprost 0.01% topically as monotherapy once daily. Ocular hyperemia was graded by the investigator at baseline and weeks 6 and 12 using a photographic five-point grading scale. Change in IOP from baseline was also evaluated at these time points. This analysis includes only the subgroup of 522 subjects who were naïve to IOP-lowering medication prior to the study.Results: After 12 weeks of treatment with bimatoprost 0.01%, hyperemia was graded as none-to-mild (grades 0, +0.5, or +1) for 93.3% of subjects and as moderate-to-severe (grades +2 or +3) for 6.7%. At weeks 6 and 12, most subjects (93.2% and 93.5%) had no change in hyperemia grade from baseline. IOP was reduced by 7.4 mmHg (29.8%) at week 6 and 7.7 mmHg (30.9%) at week 12 from baseline.Conclusion: This real-world, observational study found that bimatoprost 0.01% instilled once daily reduced IOP by a mean of 30% from baseline without moderate or severe ocular hyperemia in 93% of treatment-naïve subjects with POAG or OHT.Keywords: glaucoma, intraocular pressure, hyperemia, bimatopros

An observational study of bimatoprost 0.01% in patients on prior intraocular pressure-lowering therapy: the Canadian Lumigan® RC Early Analysis Review (CLEAR) trial

Andrew C Crichton,1 Donald R Nixon,2 Susan Simonyi,3 Meetu Bhogal,3 Christopher S Sigouin,4 Marino J Discepola,5 Cindy ML Hutnik,6 Darryl C Baptiste,3 David B Yan7 On behalf of the CLEAR Study Group 1Division of Ophthalmology, University of Calgary, Calgary, AB, Canada; 2Private practice, Barrie, ON, Canada; 3Medical Affairs, Allergan Inc., Markham, ON, Canada; 4CLINWest Research, Burlington, ON, Canada; 5Department of Ophthalmology, McGill University, Montreal, QC, Canada; 6Department of Ophthalmology and Pathology, Ivey Eye Institute, London, ON, Canada; 7Department of Ophthalmology, University of Toronto, Toronto, ON, Canada Purpose: To evaluate the ocular hyperemia and intraocular pressure (IOP)-lowering efficacy of bimatoprost 0.01% in subjects with elevated IOP due to primary open-angle glaucoma (POAG) or ocular hypertension (OHT) in a real-world clinical setting. Subjects and methods: This open-label, 12-week, observational study was conducted at 67 centers in Canada. Subjects with elevated IOP due to POAG or OHT instilled bimatoprost 0.01% as monotherapy once daily. Ocular hyperemia was graded by the investigator at baseline, week 6, and week 12 using a standardized photographic 5-point grading scale. Change in IOP from baseline was also evaluated at these time points. This analysis includes the subgroup of 268 subjects who had been previously treated with latanoprost 0.005%, bimatoprost 0.03%, travoprost 0.004%, and travoprost 0.004% with SofZia™ or nonselective beta-adrenergic receptor blockers prior to the study. Results: After 12 weeks of treatment with 0.01% bimatoprost, ocular hyperemia was graded as none-to-mild hyperemia (grades 0, +0.5, or +1) for 94.1% of subjects and as moderate-to-severe hyperemia (grades +2 or +3) for 5.9%. No statistically significant shifts in ocular hyperemia ratings were observed at week 12 for any of the prior IOP-lowering therapies except bimatoprost 0.03%, in which 20.8% of subjects experienced an improvement. The mean percentage change from baseline IOP at week 12 following the switch to bimatoprost 0.01% monotherapy ranged from –2.3%±17.3% to –26.3%±12.4%. Furthermore, the decreased mean percentage change from baseline IOP was statistically significant across all prior IOP-lowering medications, except for bimatoprost 0.03% at the 6- and 12-week visits and travoprost 0.004% at the 6-week visit. Conclusion: This observational study demonstrates that bimatoprost 0.01% was well tolerated among POAG and OHT subjects who switched from prior IOP-lowering medication. Furthermore, a switch in ocular hypertensive treatment to bimatoprost 0.01% was associated with an additional 10%–15% reduction in IOP. Keywords: glaucoma, intraocular pressure, hyperemia, bimatopros

Cognitive improvement after treatment of depressive symptoms in the acute phase of stroke Melhora cognitiva com tratamento antidepressivo na fase aguda do acidente vascular cerebral

The outcome of antidepressant treatment for depressive symptoms and cognitive impairment at the acute phase of stroke is controversial. We investigated 93 patients, treating with citalopram 36 with severe depressive symptoms (HAM-D: Hamilton Depression Rating Scale >18), whilst 19 patients with mild depressive symptoms, and 38 non-depressed patients, remained untreated. At baseline (two weeks after stroke), patients with severe depressive symptoms had lower scores in total Dementia Rating Scale (DRS) and in the attention and memory DRS subscales, than the non-depressed patients (p<0.001). At the end of the three-month follow-up period, these differences had disappeared, but patients initially with mild depressive symptoms had higher HAM-D scores than the non-depressed patients (p=0.015), and lower scores in DRS attention and memory subscales (p<0.01), than the patients treated with citalopram. Treatment was associated with improved mood, memory and attention, and a placebo-controlled study on the treatment of mild depressive symptoms is warranted.<br>Os resultados do tratamento com antidepressivo para os sintomas depressivos e comprometimento cognitivo da fase aguda do acidente vascular cerebral não estão estabelecidos. Investigamos 93 pacientes, 36 com sintomas depressivos graves (HAM-D: Escala de Depressão de Hamilton >18) foram tratados com citalopram, enquanto 19 pacientes com sintomas depressivos leves e 38 não-deprimidos não foram tratados. Ao início do tratamento (duas semanas depois do icto), pacientes com sintomas depressivos graves tinham escores mais baixos na Escala de Avaliação de Demência (DRS) total e nas subescalas de atenção e de memória da DRS do que os pacientes não-deprimidos (p<0,001). Ao fim de três meses de acompanhamento essas diferenças tinham desaparecido, mas pacientes que inicialmente tinham sintomas depressivos leves passaram a ter escores mais altos no HAM-D do que os não-deprimidos (p=0,015), e escores mais baixos nas subescalas de atenção e memória da DRS (p<0,01) do que os pacientes tratados com citalopram. O tratamento associou-se a melhora de humor, memória e atenção, e demonstra que é necessário um estudo controlado com placebo para o tratamento de sintomas depressivos leves