Biomedical subjects

S Gabriel

Publications and source records attributed to S Gabriel.

At least 19 recordsLinked to original sources

PubMed2007

Time frame and predictors of recovery from disability following recurrent ischemic stroke.

OBJECTIVE: To assess the rate, degree, and predictors of recovery from a disabled to nondisabled state in patients disabled after recurrent ischemic stroke. METHODS: Patients with ischemic stroke enrolled in the Management of Atherothrombosis with Clopidogrel in High Risk Patients (MATCH) Study underwent prospective assessment of their modified Rankin score (mRS) at 1, 3, 6, 12, and 18 months after enrollment and after recurrent stroke. Patients disabled (defined as mRS > or = 3) after recurrence were analyzed for recovery (defined as mRS < 3) during the 18 months, and predictors of recovery were sought using a Cox proportional-hazard multiple regression analysis. RESULTS: Three hundred forty-five (54%) of 637 patients were disabled after recurrent ischemic stroke; 115 (33%) patients had been disabled and 230 (66%) nondisabled before stroke recurrence. At recurrence, the degree of disability was moderate (mRS 3) in 135 (39%) patients, severe (mRS 4) in 139 (40%), and very severe (mRS 5) in 71 (21%). After 12 months' median follow-up, 117 (34%, 95% CI: 29 to 39%) had recovered: 68 (50%, 42 to 59%) of 135 moderately disabled, 45 (32%, 25 to 41%) of 139 severely disabled, and 4 (6%, 2 to 14%) of 71 very severely disabled; 70 (20.3%) patients died. From recurrence, median time to recovery was 6 months (mRS 3) and 18 months (mRS 4); 94% with very severe disability had not recovered at 18 months. Independent predictors of recovery were moderate disability at recurrence (mRS 3) compared with severe (mRS 4: hazard ratio [HR] 1.5; 95% CI 1.04 to 2.3) or very severe disability (mRS 5: HR 7.6; 2.7 to 20) and a nondisabled vs disabled state before recurrence (HR 4.0; 2.3 to 6.8). CONCLUSIONS: The rate of recovery from recurrent ischemic stroke was greatest in the first 6 months; one-third of patients recovered within 12 months. The significant predictors of recovery were a nondisabled state before recurrence and increasing severity of the recurrent stroke.

Activities of Daily Living↗

PubMed2006

Prevalence and genotyping of Cryptosporidium in three cattle husbandry systems in Zambia.

To estimate the prevalence of Cryptosporidium spp. in three different husbandry systems in Zambia, faecal samples were collected from calves up to the age of 3 months. Faecal consistency was scored for correlation with infection. Additionally, 45 positive samples were selected for genotyping by amplification of the 70-kDa heat shock protein (HSP-70) and the 18S rRNA gene. A total of 37 dairy, 25 beef and 92 traditional husbandry farms were visited: 250 samples were collected on dairy farms, 238 on beef farms and 256 on traditional husbandry farms. All samples were analysed using a commercial copro-antigen ELISA (Techlab)(Cryptospridium test). The calf prevalence in dairy, beef and traditional husbandry systems was 42.8%, 8.0% and 6.3%, respectively. Furthermore, 75.7% of the dairy farms, 44.0% of the beef farms and 15.2% of the traditional husbandry farms had at least one positive calf at the time of visit. Subsequently, there was a significantly higher Cryptosporidium parvum prevalence on dairy farms compared to beef or traditional farms (chi(2), P<0.001). On dairy farms low faecal consistency was correlated with C. parvum infection (chi(2), P<0.05). Both C. parvum and C. bovis were identified, although in one beef calf C. suis was found.

Age Factors↗

PubMed2006

Cost-consequence analysis in a French setting of screening and optimal treatment of nephropathy in hypertensive patients with type 2 diabetes.

AIM: Forty percent of hypertensive type 2 diabetes patients develop nephropathy (microalbuminuria/overt nephropathy), indicating end organ damage, increased risk of cardiovascular disease (CVD), and death. In France, screening rates and nephropathy treatment are suboptimal. We assessed the health economic impact of nephropathy screening in hypertensive patients with type 2 diabetes followed by optimal antihypertensive/nephroprotective therapy in those who have nephropathy in France. METHODS: A Markov/Monte Carlo model simulated lifetime impacts of screening for albuminuria (microalbuminuria/overt nephropathy) using semi-quantitative urine dipsticks in a primary care setting, and subsequent addition of irbesartan 300 mg to conventional therapy in hypertensive type 2 diabetes patients identified as having nephropathy. Progression from no renal disease to end-stage renal disease (ESRD) was simulated. Probabilities, utilities and costs of CVD events, medications and ESRD treatment came from published sources. Cumulative incidence of ESRD, life expectancy, quality-adjusted life years (QALYs) and direct costs were projected. Second-order Monte Carlo simulation accounted for uncertainty in multiple parameters. Costs and QALYs were discounted at 3% annually. RESULTS: Screening and optimized treatment led to a 42% reduction in the cumulative incidence of ESRD from 10.1 +/- 9.9% without screening to 5.8 +/- 5.7%, improvements in life expectancy of 0.38 +/- 0.59 years, improvements of 0.29 +/- 0.32 QALYs, and decreased costs of Euro 4,812 +/- 7,882/patient over 25 years. Sensitivity analysis showed that the results were robust. Screening was most beneficial when performed in younger patients. CONCLUSION: In hypertensive patients with type 2 diabetes, screening for albuminuria followed by optimal antihypertensive/nephroprotective treatment improves patient outcomes and leads to cost savings in France.

Adult↗

PubMed2006

Assessment of routine inspection methods for porcine cysticercosis in Zambian village pigs.

The value of tongue and meat inspection as diagnostic tools for porcine cysticercosis was assessed in 65 Zambian village pigs by comparing the results with carcass dissections. In addition, the intensity of infections, distribution and viability of cysts in infected pigs were measured. Five pigs (7.7%) were positive on tongue examination, while routine meat inspection showed 12 (18.5%) positives. However, carcass dissections detected cysticerci in 31 (47.7%) pigs. The range in number of cysticerci was 1 to 14,662 per carcass. Cysticerci were distributed throughout the carcass with the highest concentration in the heart, tongue and hind legs. In one animal 13 viable cysts were detected only in the brain. Fourteen pigs had more than 100 viable cysts, six between 2 and 100, and four had single cyst infections. Seven animals harboured only calcified cysts. These findings demonstrate the serious shortcomings of routine detection methods for porcine cysticercosis. While the specificity of tongue palpation and meat inspection was 100%, these tests failed to detect the infection in 83.9% and 61.3% of infected pigs, respectively.

Animals↗

PubMed2005

Entorhinal cortex entrains epileptiform activity in CA1 in pilocarpine-treated rats.

Layer III neurons of the medial entorhinal cortex (mEC) project to CA1 via the temporoammonic pathway and exert a powerful feed-forward inhibition of CA1 pyramidal neurons. The present study evaluates the hypothesis that disrupted inhibition of CA1 pyramidal neurons causes an eased propagation of entorhinal seizures to the hippocampus via the temporoammonic pathway. Using a method to induce a confined epileptic focus in brain slices, we investigated the spread of epileptiform activity from the disinhibited mEC to CA1 in control and pilocarpine-treated rats that had displayed status epilepticus and spontaneous recurrent seizures. In pilocarpine-treated rats, the mEC showed a moderate layer III cell loss and an enhanced susceptibility to epileptiform discharges compared to control animals. Entorhinal discharges propagated to CA1 in pilocarpine-treated rats but not in controls. Disconnecting CA3 from CA1 did not affect the spread of epileptiform activity to CA1 excluding its propagation via the trisynaptic hippocampal loop. Mimicking the invasion of epileptiform discharges by repetitive stimulation of the temporoammonic pathway caused a facilitation of field potentials in CA1 that were contaminated by population spikes and afterdischarges in pilocarpine-treated but not control rats. Single cell recordings of CA1 pyramidal neurons revealed a dramatic loss of feed-forward inhibition and the occurrence of strong postsynaptic excitatory potentials in pilocarpine-treated rats. Excitatory responses in CA1 were characterized by multiple NMDA receptor-mediated afterdischarges and a strong paired-pulse facilitation in response to activation of the temporoammonic pathway. Our results suggest that, irrespective of the enhanced seizure-susceptibility of the mEC in epileptic rats, the loss of feed-forward inhibition and the enhanced NMDA receptor-mediated excitability CA1 pyramidal cells ease the spread of epileptiform activity from the mEC to CA1 via the temporoammonic pathway bypassing the classical trisynaptic hippocampal loop.

Animals↗

PubMed2004

A Bayesian approach for estimating values for prevalence and diagnostic test characteristics of porcine cysticercosis.

Several diagnostic techniques are used to estimate the prevalence of the zoonotic tapeworm Taenia solium in pigs, but none of these tests are perfect, making interpretation of results difficult. A Bayesian approach was used to estimate values for the prevalence and diagnostic test characteristic of porcine cysticercosis by combining results of four imperfect tests. Village pigs (N = 868) slaughtered in Lusaka (Zambia), were bled, and tongue and routine meat inspected; and serum antibody and parasite antigen concentrations were determined by ELISA. A model, based on a multinomial distribution and including all possible interactions between the individual tests required 31 parameters to be estimated, but actually allowed only 15 parameters (i.e. had 15 degrees of freedom) to be estimated. Therefore, prior expert opinion on specificity and (in)-dependence of the tests was entered in the model, resulting in a reduction of the number of parameters to be estimated. The estimated prevalence of porcine cysticercosis was 0.642 (95% confidence interval 0.54-0.91). The performances of the tests were (sensitivity (se)-specificity (sp)): tongue inspection (se 0.210-sp 1.000), meat inspection (se 0.221-sp 1.000), Ab-ELISA (se 0.358-sp 0.917), Ag-ELISA (se 0.867-sp 0.947). To validate the estimates obtained from the model we performed a second study: 65 randomly purchased Zambian village pigs were bled for serum antibody and antigen determination, their tongue and meat inspected; and in addition, the carcasses were dissected for total cysticercus counts (gold standard). Cysticerci were found in 31 pigs (prevalence 0.477, 95% confidence interval 0.35-0.60), overlapping with the estimated prevalence in the first study. Sensitivity and specificity values obtained for the aforementioned tests in this study were in agreement with those estimated. A Bayesian analysis framework offers the possibility to combine prior opinion with experimental data to more accurately estimate the real prevalence of porcine cysticercosis in the absence of a gold standard.

Animals↗

PubMed2004

Modulation of connexin expression in sheep endometrium in response to pregnancy.

The expression pattern of two typical gap junction channel proteins, connexin 43 and connexin 26 (Cx43 and Cx26), was identified in the endometrium of sheep, a species with epitheliochorial type of implantation, by indirect immunohistochemistry during the cyclic phases, early and late pregnancy, and immediately after birth. The extent of Cx43 immunoreaction bound to endometrial stromal cells of the early implantation stage (day 15 p.c.) was comparable to the situation observed in oestrus. The subsequent intensification of feto-maternal contact correlated with a striking increase of stromal Cx43 in the intercaruncular and caruncular regions of the uterus (days 18 and 21 p.c.) and the induction of Cx26 in the glandular epithelium of late implantation (day 21 p.c.). In contrast, both gap junction proteins, coexpressed in the stroma of placentomes and interplacentomal sections on days 131 and 145 p.c., decreased during late pregnancy, while an intense and augmenting staining for Cx26 was detected at the cell borders of the glandular and luminal epithelium. The spatial and temporal distribution of both connexins suggests that, under embryonal and hormonal influences, gap junctional communication is involved in the implantation process and the regulation of endometrial tissue functions during sheep pregnancy and indicates further, that this connexin expression path resembles more the invasive type of implantation.

Animals↗

PubMed2003

Preparation of reactive surfaces by electrografting.

The electrografting process has been applied to a new monomer in order to induce reactivity to the surface of various conducting substrates which are then appropriate for the anchoring of a large variety of molecules (catalysts, proteins, amino-polymers etc.).

Journal Article↗

PubMed2002

The prevalence of porcine cysticercosis in Eastern and Southern provinces of Zambia.

The objective of this study was to determine the prevalence and importance of porcine cysticercosis in rural areas of Zambia. The study involved an abattoir survey of 1316 pigs at a slaughter slab in Lusaka and two field surveys in villages in Southern and Eastern provinces. Lingual examination of live pigs and visual inspection of their carcass as well as blood sampling for measuring circulating parasite antigen by enzyme-linked immunosorbent assay (Ag-ELISA) were used as parameters to measure infection. In the field surveys, a questionnaire was administered to every household whose pigs were examined to obtain information on pig husbandry practices and to study risk factors for the infection. Out of the 1316 pigs examined at the slaughter slab, 143 (10.9%) and 271 (20.6%) were positive by lingual examination and meat inspection, respectively. Most of the pigs were very heavily infected with predominantly live cysts. The field surveys revealed that eight (8.2%) out of 98 pigs from Southern province and eight (5.2%) out of 151 pigs from Eastern province were positive for cysticercosis by tongue palpation. Using the Ag-ELISA 20 (20.8%) and 14 (9.3%) pigs were positive in Southern and Eastern provinces, respectively. The questionnaire survey revealed poor pig husbandry practices, absence of meat inspection and control, poor knowledge of the disease and poor sanitation in the surveyed villages. The prevalence of pig cysticercosis found in this study ranks among the highest in the southern African region, in Africa and in the world. The current study suggests the presence of human tapeworm carriers and a high risk of human cysticercosis in the surveyed areas as well as in urban centres where pigs from rural areas are increasingly sold, slaughtered and consumed.

Abattoirs↗

PubMed2002

A sero-epidemiological study of bovine cysticercosis in Zambia.

A sero-epidemiological study of Taenia saginata cysticercosis was carried out in adult cattle in Zambia to determine the prevalence and study the influence of the farming system on the infection rate. Serum samples were examined for circulating parasite antigen by a monoclonal-based sandwich ELISA. Thirty-eight of 628 serum samples were found positive (prevalence 6.1%). Cysticercosis was significantly more prevalent in feedlots and in traditional farming systems than in dairy farms. It is suggested that the continuous man to animal contact and the use of casual workers in feedlots may be factors that are conductive to T. saginata transmission.

Animal Husbandry↗

PubMed2002

Cell death and metabolic activity during epileptiform discharges and status epilepticus in the hippocampus.

Mechanisms of seizure-induced cell death were studied in organotypic hippocampal slice cultures. These develop after withdrawal of magnesium recurrent seizure-like events (SLE), which lead to intracellular and intramitochondrial calcium accumulation. The intramitochondrial Ca accumulation seems to be involved in causing increased production of NADH, measured as NAD(P)H autofluorescence. During SLEs, depolarization of mitochondria and increased production of free radicals is indicated by fluorescence measurements with appropriate dyes. During recurrent seizures, an increased failure to produce NADH is noted while at the same time free radical production seems to increase. This increase and the decline in NADH production could be involved in transition to late recurrent discharges, a phase in which status epilepticus becomes pharmacoresistant. It also coincides with increased cell death as determined with propidium iodide fluorescence. Interestingly, some of these changes can be prevented by application of alpha-tocopherol, a free radical scavenger, which also has neuroprotective effects under our experimental conditions. The results suggest that free radical-induced mitochondrial impairment is involved in seizure-induced cell death.

Animals↗

PubMed2002

Coupling of electrical and metabolic activity during epileptiform discharges.

Changes in electrical activity, ionic microenvironments, and intracellular Ca concentration were measured during recurrent seizures induced by low Mg in slices and slice cultures. In both preparations, initial seizure-like events (SLEs) changed after some time into drug-refractory late recurrent discharges. In slice cultures, there was considerable cell loss in all hippocampal areas after 2 h of status epilepticus. During recurrent SLEs, the NAD(P)H autofluorescence declined, as did intramitochondrial calcium signals, indicating mitochondrial damage. At the same time, ethidium signals indicated increased radical oxygen species production. These alterations could be reduced by alpha-tocopherol, which also protected slice cultures against status epilepticus-induced cell death.

Animals↗

PubMed2001

Single nucleotide polymorphisms in multiple novel thrombospondin genes may be associated with familial premature myocardial infarction.

BACKGROUND: Recent advances in high-throughput genomics technology have expanded our ability to catalogue allelic variants in large sets of candidate genes related to premature coronary artery disease. METHODS AND RESULTS: A total of 398 families were identified in 15 participating medical centers; they fulfilled the criteria of myocardial infarction, revascularization, or a significant coronary artery lesion diagnosed before 45 years in men or 50 years in women. A total of 62 vascular biology genes and 72 single-nucleotide polymorphisms were assessed. Previously undescribed variants in 3 related members of the thrombospondin protein family were prominent among a small set of single-nucleotide polymorphisms that showed a statistical association with premature coronary artery disease. A missense variant of thrombospondin 4 (A387P) showed the strongest association, with an adjusted odds ratio for myocardial infarction of 1.89 (P=0.002 adjusted for covariates) for individuals carrying the P allele. A variant in the 3' untranslated region of thrombospondin-2 (change of thymidine to guanine) seemed to have a protective effect against myocardial in individuals homozygous for the variant (adjusted odds ratio of 0.31; P=0.0018). A missense variant in thrombospondin-1 (N700S) was associated with an adjusted odds ratio for coronary artery disease of 11.90 (P=0.041) in homozygous individuals, who also had the lowest level of thrombospondin-1 by plasma assay (P=0.0019). CONCLUSIONS: This large-scale genetic study has identified the potential of multiple novel variants in the thrombospondin gene family to be associated with familial premature myocardial infarction. Notwithstanding multiple caveats, thrombospondins specifically and high-throughput genomic technology in general deserve further study in familial ischemic heart disease.

Adult↗

PubMed2001

Mild postischemic hypothermia is neuroprotective in the immature rat neocortex slice.

Mild hypothermia as an intervention after perinatal asphyxia may prevent neurological damage in the newborn. We used stimulus-induced field potentials to monitor recovery from oxygen and glucose deprivation (OGD) in neocortex slices of 6-8-day-old wistar rats. OGD after a latency of 10.7+/-2.1 min (mean+/-S.E.) resulted in an anoxic depolarisation with an amplitude of 5.4+/-2.4 mV. Mild hypothermia of 31 degrees C (vs. 35 degrees C in the control group) was applied for 60 min after end of OGD. The 20, 40, 60 and 80% recovery of the field potential amplitude was significantly faster in the hypothermia group in comparison to the control group. These data indicate that mild postischemic hypothermia may have neuroprotective effects after perinatal asphyxia.

Animals↗

PubMed2001

High oxygen tension leads to acute cell death in organotypic hippocampal slice cultures.

Increased oxygen tension in the central nervous system can be of relevance in different clinical situations, e.g. hyperbaric oxygen treatment during resuscitation of newborns in asphyxia as well as during seizures in children and adults where the supply of oxygen to tissue is increased by elevated cerebral blood flow. We focused on changes in neuronal tissue by investigating the impact of different oxygen tensions on juvenile rat hippocampal slice cultures using extracellular field potential recordings and propidium iodide (PI) staining for cell death determination. Slice cultures were prepared following the Stoppini technique (postnatal days 6-8). Electrophysiological responses in area CA1 to hilar stimulation were recorded every 15 min after an initial equilibration period of 60 min. Slice cultures maintained in 95% oxygen showed a 53% (S.E.M.=17%; n=10) run-down in amplitudes of the evoked responses over the observation time course of 90 min. In contrast, slice cultures maintained in 19% oxygen showed no run-down in amplitudes (S.E.M.=9%; n=18). PI staining of the slice cultures carried out immediately after the electrophysiological measurements indicated a dramatic cell death rate in the high oxygen tension group compared to those maintained in 19% oxygen. Interestingly, epileptiform activity (seizure-like events, spreading depression-like events) occurred in some slice cultures dependent on oxygen tension. Altered paired-pulse index of evoked responses suggests a loss of GABAergic function, especially in the 95% oxygen tension group. These results demonstrate a high sensitivity to oxygen in juvenile rat hippocampal slice cultures, in contrast to acutely prepared juvenile and adult rat hippocampal slices.

Animals↗

PubMed2001

Ca2+ signalling and changes of mitochondrial function during low-Mg2+-induced epileptiform activity in organotypic hippocampal slice cultures.

Several lines of evidence indicate that augmented neuronal activity is associated with increased mitochondrial function, however, the mechanisms of coupling are still unclear. In this study we used a low extracellular Mg2+ concentration and short stimulus trains to evoke neuronal hyperactivity in the form of seizure-like events (SLE) in hippocampal slice cultures. Simultaneous microfluorimetric and electrophysiological techniques were applied to gain insight into changes of Ca2+ concentration in different compartments and into mitochondrial function. SLEs were associated with a large decrease of the extracellular Ca2+ concentration ([Ca2+]e), a spiking increase of the cytoplasmic and a smoothed elevation of the mitochondrial Ca2+ concentration (cytoplasmic concentration [Ca2+]i; intramitrochondrial concentration [Ca2+]m). Following an initial apparent decline in the mitochondrial membrane potential (DeltaPsi) and NAD(P)H autofluorescence, mitochondria depolarized and NADH production was augmented. Furthermore, SLEs were associated with increased oxidation of dihydroethidine (HEt). Our data suggest that intramitochondrial Ca2+ accumulation stimulates NADH production and production of radical oxygen species (ROS). Interestingly, mitochondrial depolarization followed [Ca2+]i and [Ca2+]m changes with a delay implying that electrogenic extrusion of Ca2+ from the mitochondrial matrix might be responsible for the depolarization of the mitochondrial membrane.

Animals↗

PubMed2001

Fluorescent tracer in pilocarpine-treated rats shows widespread aberrant hippocampal neuronal connectivity.

Neuronal fibres of the hippocampal formation of normal and chronic epileptic rats were investigated by fluorescent tracing methods using the pilocarpine model of limbic epilepsy. Two months after onset of spontaneous limbic seizures, hippocampal slices were prepared and maintained in vitro for 10 h. Small crystals of fluorescent dye [fluorescein (fluoro-emerald) and tetramethylrhodamine (fluoro-ruby)] were applied to different hippocampal regions. The main findings were: (i) in control rats there was no supragranular labelling when the mossy fibre tract was stained in stratum radiatum of area CA3. However, in epileptic rats a fibre network in the inner molecular layer of the dentate gyrus was retrogradely labelled; (ii) a retrograde innervation of area CA3 by CA1 pyramidal cells was disclosed by labelling remote CA1 neurons after dye injection into the stratum radiatum of area CA3 in chronic epileptic rats; (iii) labelling of CA1 neurons apart from the injection site within area CA1 was observed in epileptic rats but not in control animals; and (iv), a subicular-hippocampal projection was present in pilocarpine-treated rats when the tracer was injected just below the stratum pyramidale of area CA1. The findings show that fibre rearrangement in distinct regions of the epileptic hippocampal formation can occur as an aftermath of pilocarpine-induced status epilepticus.

Action Potentials↗

PubMed2001

Issues of consensus and debate for economic evaluation in rheumatology.

We report initial attempts at developing standards for the conduct of economic evaluations in rheumatology. We surveyed 25 clinicians and economists with an interest in rheumatology regarding the design and reporting of economic evaluations, with particular reference to 4 clinical scenarios relating to treatment for rheumatoid arthritis, osteoarthritis, and osteoporosis. The results demonstrated widespread agreement on a number of methodological issues such as statement of funding source, perspective, discounting, and allowance for uncertainty. However, there was lack of consensus over clinical variables including sources of data for efficacy estimates, specific clinical outcomes, methods of assessing quality of life, and choice of comparators. Some of the disagreement reflects lack of consensus in current general methodological guidelines. Consensus regarding the disease-specific clinical variables is crucial to standardizing analysis and facilitating comparisons within clinical scenarios.

Antirheumatic Agents↗