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Biomedical subjects

A Ameri

Publications and source records attributed to A Ameri.

At least 55 records · Page 3Linked to original sources
PubMed1996

Electrophysiological effects of aconitine in rat hippocampal slices.

The electrophysiological effects of aconitine were investigated in the rat hippocampal slice and compared with those of veratridine. Both alkaloids are known to bind at site 2 of sodium channels and to block its inactivation. Extracellular recordings revealed that aconitine and veratridine exert inhibitory effects on neuronal excitability. Aconitine slowly and reversibly decreased the population spike recorded in the CA1 pyramidal cell layer. The reduction of the spike amplitude was similar whether orthodromically or antidromically activated. The aconitine-induced inhibition did not differ from that of veratridine. However, following washout of aconitine, the amplitude of the antidromic spike was increased compared to the control amplitude. The veratridine-induced inhibition was only partially reversible. This inhibition was also observed during suppression of synaptic transmission by a low Ca2+/high Mg2+-medium, indicating an inhibition of axonal conductance. The results show that in the absence of synaptic transmission the antidromic (alvear) spike is more sensitive to the inhibitory action of aconitine than the presynaptic fiber spike elicited by stimulation of the Schaffer collaterals. Furthermore, it is shown that aconitine acts in an activity-dependent manner, in that the latency of onset of the inhibition is prolonged when the stimulation frequency is decreased. Field excitatory postsynaptic potentials were also suppressed by aconitine, whereas excitatory postsynaptic currents recorded by the patch clamp technique were not influenced by aconitine when cells were held at -60 mV.

Aconitine↗
PubMed1996

Treatment of recurrent malignant supratentorial gliomas with ifosfamide, carboplatin and etoposide: a phase II study.

Thirty-six patients previously treated with surgery, radiation therapy and chemotherapy with a nitrosourea for malignant supratentorial gliomas received a combination of ifosfamide, carboplatin and etoposide (ICE) at tumour progression. Carboplatin and etoposide were both given at a dose of 75-100 mg/m2/day for 3 days, whereas ifosfamide doses ranged from 750 mg/m2/day to 1500 mg/m2/ day for 3 days, according to haematological tolerance. Treatment was repeated every 4 weeks. A minimum of three courses was required to evaluate the response unless the patient had rapid tumour progression. Grade III and IV haematological toxicity occurred in 15 patients (42%) and was lethal in one patient. Grade II hepatic toxicity was observed in one patient. Five complete (CR) and five partial responses (PR) were noted. 9 patients had stable disease (SD) after a minimum of three courses. CR + PR + SD was 53% (19/36). The median time to tumour progression (MTTP) was 13 weeks. Median survival (MST) was 29 weeks (44 weeks for R + S patients and 17 weeks for patients with progressing disease). This study suggests that the ICE combination is active in recurrent supratentorial malignant gliomas after failure of surgery, radiation therapy and chemotherapy, but at the cost of substantial haematological toxicity.

Adult↗
PubMed1996

Frequency-dependent inhibition of neuronal activity by lappaconitine in normal and epileptic hippocampal slices.

1. Extracellular recording of the stimulus-evoked population spike in the CA1 region of rat hippocampal slices in vitro was performed in order to investigate whether lappaconitine affects neuronal excitability. Lappaconitine is a diterpene alkaloid of plants of the Aconitum genus and has analgesic properties. 2. The results reveal an inhibitory action of lappaconitine (10 microM) manifested in a slow attenuation of the orthodromic and antidromic population spike. 3. The lappaconitine-induced inhibitory action was activity-dependent, that is, it was potentiated when frequency of electrical stimulation was increased. In contrast, washout of the neurotoxin was accelerated when stimulation frequency was decreased. 4. The activity-dependent action of lappaconitine raised the question of whether the drug is effective in suppressing the aberrant neuronal activity that occurs during an epileptic seizure. The results obtained from experiments on epileptic hippocampal slices demonstrated a selective reduction of the later spikes in the bursts with less effect on normal neuronal activity. 5. These data support the conclusion that lappaconitine, in addition to its antinociceptive effect, also has antiepileptic potency due to its highly activity-dependent mode of action.

Aconitine↗
PubMed1996

Coagulation studies, factor V Leiden, and anticardiolipin antibodies in 40 cases of cerebral venous thrombosis.

BACKGROUND AND PURPOSE: Cerebral venous thrombosis (CVT) is an infrequent condition with a large variety of causes. However, in 20% to 35% of cases, no cause is found. We studied coagulation parameters, including activated protein C resistance associated with factor V gene mutation (factor V Leiden) and anticardiolipin antibodies, in a large series of patients with CVT with or without identified cause or risk factor. METHODS: Forty patients (30 women and 10 men) aged 19 to 71 years (mean age, 36.2 years) with CVT diagnosed by angiography and/or MRI were studied 1 to 18 years after thrombosis. No known cause was found in 10 idiopathic cases. Coagulation studies included the following tests: fibrinogen, antithrombin, protein C, protein S, plasminogen, anticardiolipin antibodies, activated protein C resistance, and factor V Leiden. RESULTS: Six cases of thrombophilia (15%) were found: 1 protein C deficiency, 1 protein S deficiency, and 4 activated protein C resistance with heterozygous factor V Leiden mutation (10%). Only 1 case (protein S deficiency) was found in the group of 10 patients with idiopathic CVT. In the other 5, there was another cause or risk factor. Three patients (8%) had increased anticardiolipin antibodies: 1 with systemic lupus and 2 with primary antiphospholipid syndrome; 2 of these 3 patients also had factor V Leiden mutation. CONCLUSIONS: Although present in a number of CVT cases, acquired (anticardiolipin) or congenital varieties of thrombophilia (factor V Leiden being the most frequent) are almost invariably associated with other predisposing factors. This suggests that (1) these abnormalities should be looked for in patients with CVT, whether a cause is found or not, and (2) their presence should not deter the search for other potential causes. The detection of such abnormalities has major practical consequences on the long-term management of patients to prevent further thrombotic episodes.

Adult↗
PubMed1996

Long-term prognosis in cerebral venous thrombosis. Follow-up of 77 patients.

BACKGROUND AND PURPOSE: Very little is known about the long-term outcome of patients with cerebral venous thrombosis (CVT), particularly regarding the risk of residual epilepsy and further thrombotic events. We retrospectively studied 77 patients with CVT diagnosed by angiography and/or MRI. METHODS: A cohort of 77 patients aged 18 to 77 (mean, 38.5) years with CVT, evaluated from 1975 through 1990, was followed up for a mean of 77.8 months (range, 14 to 204 months; median, 63 months). Information on death, neurological status, seizures, recurrent CVT, other thrombotic events, and subsequent pregnancies was obtained from direct observation, mail questionnaire, or telephone interviews. RESULTS: Sixty-six of 77 patients (85.7%) had no neurological sequelae during follow-up. Eleven patients (14.3%) remained neurologically impaired. Two who initially presented with isolated intracranial hypertension had blindness due to optic atrophy. The other 9 had focal signs at the time of CVT and were left with various cognitive or focal deficits. Four of 28 (14.3%) patients who had seizures at the acute stage had recurrent seizures. One of the 51 patients with lateral sinus thrombosis developed a dural arteriovenous fistula. Nine of the 77 patients (11.7%) suffered a second CVT, all but one in the first year. Noncerebral thrombotic events occurred in 11 patients (14.3%). No recurrence of CVT occurred during later pregnancies, but 1 patient had a postpartum deep vein thrombosis. CONCLUSIONS: In the present series, CVT has an essentially good long-term prognosis. The frequency of long-standing epilepsy was low, suggesting that long-term anticonvulsant treatment is not necessary in the majority of cases. A second CVT or another thrombotic episode occurred in 20% of patients, stressing the need in a minority of cases for long-term anticoagulation.

Adolescent↗
PubMed1995

Primary central nervous system lymphoma: treatment with chemotherapy and radiotherapy.

Between 1989 and 1993, 22 HIV negative patients with primary central nervous system lymphoma (PCNLS) were treated with three different regimens. In group A, 13 patients received preradiotherapy systemic and intrathecal methotrexate (MTX), radiotherapy (RT) and three courses of post-RT chemotherapy (CT) with thiotepa and procarbazine. In group B, 4 patients received a similar CT only after RT and without intrathecal MTX in 3/4 cases. In group C, 5 elderly patients received CT alone. In group A, 9/13 patients achieved response after pre-RT CT and 12/13 were in complete response (CR) after RT. After a median follow-up of 27 months, 8/13 (62%) patients are alive but 4 have leucoencephalopathy and cognitive dysfunction. In group B, all 4 patients were in CR after RT but the 3 patients who did not receive intrathecal MTX died within 10 months with meningeal recurrence. In group C, 4/5 patients had a response to CT. 2 patients died of recurrent tumour at 5 and 10 months, and 2 are living in CR 11+ and 21+ months after diagnosis, 1 after salvage CT. Combined treatment with RT and CT is useful in PCNSL but adequate treatment of the meninges is required. CT alone is sometimes of value in elderly patients in whom RT is not indicated.

Adult↗
PubMed1995

Tissue factor pathway inhibitor and von Willebrand factor antigen levels in adult respiratory distress syndrome and in a primate model of sepsis.

Tissue factor pathway inhibitor (TFPI) is an anticoagulant protein primarily synthesized by the endothelium. A major fraction (approximately 85%) of TFPI remains associated with the endothelium, whereas a small fraction (approximately 15%) is secreted into the blood. In our attempts to search for a marker(s) of endothelial injury in the setting of adult respiratory distress syndrome (ARDS), we retrospectively measured plasma TFPI levels in patients at risk for and with ARDS caused by several etiologic factors. Plasma von Willebrand factor antigen (vWF-Ag), another endothelial-specific protein, was also measured in these patients. The mean plasma TFPI levels were slightly elevated (approximately 1.3-fold), whereas vWF-Ag levels were significantly elevated (approximately 3-fold) in the at-risk group as compared with those in the normal subjects. Both the TFPI (approximately 1.8-fold) and the vWF-Ag (approximately 4-fold) levels were further elevated in the ARDS group. Moreover, the sequential plasma samples from patients with ARDS had progressively increased levels of vWF-Ag and TFPI up to Days 4 and 8, respectively. Neither plasma vWF-Ag nor TFPI levels correlated with mortality in the at-risk group or the ARDS group. TFPI levels were also measured in bronchoalveolar lavage fluids (BALF). The levels (ng/ml) were: normal subjects, 0.05 +/- 0.02 SE; at-risk group, 0.35 +/- 0.16 SE; ARDS group, 0.99 +/- 0.28 SE. Thus, the BALF TFPI levels were increased approximately 7-fold in the at-risk group and approximately 20-fold in the ARDS group relative to the value in the normal subjects. These findings indicate increased local synthesis of TFPI in the alveolar space both in the at-risk patients and in those with ARDS. In additional studies in a primate model of sepsis, lethal doses (LD100) of E. coli administered to baboons resulted in a progressive increase in TFPI levels (approximately 2-fold at 6 h), whereas sublethal doses caused only minimal increase (approximately 1.2-fold). The vWF-Ag levels were elevated approximately 5-fold after infusion of LD100 concentrations of E. coli at 6 h and 4-fold after infusion of sublethal concentrations of E. coli at 24 h. Autopsies on animals in the LD100 group revealed pulmonary congestion, leukocyte infiltration, edema, and hemorrhage, all suggestive of acute lung injury. Thus, in the setting of acute lung injury plasma vWF-Ag appears to be considerably increased prior to significant damage to the endothelium, whereas increased plasma TFPI occurs only after severe injury.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

[Cerebral venous thromboses. Clinical diagnosis].

Cerebral vein thromboses constitute a major part of cerebral venous disease. They can occur at any age, generally in young subjects, and are due to a variety of causes, although no aetiology can be detected in one quarter of cases. They generally occur in the superior sagittal sinus and transverse sinuses, while involvement of the deep veins and posterior fossa veins is much less common. The symptoms consist of varying degrees of signs of intracranial hypertension (ICH) and focal and/or epileptic signs. The onset may be sudden, subacute or chronic, simulating a cerebral vascular accident, an abscess, encephalitis, a tumour or benign ICH. Radiological investigations, especially MRI and angiography, are the key to the diagnosis. A fatal outcome is observed in 10% of non-infectious forms. The benefit of heparin therapy, although controversial for a long time, has now been clearly established.

Adrenal Cortex Hormones↗
PubMed1994

[Imaging of cerebral thrombophlebitis].

Because of the polymorphic nature of the clinical presentations observed, the diagnosis of cerebral vein thrombosis (CVT) is often difficult and based on the findings of various imaging techniques. Routine CT scan constitutes a guiding examination allowing exclusion of other diseases responsible for the clinical symptoms and signs. MRI, a noninvasive technique allowing analysis of perfusion and thrombosis would appear to be the first-line examination for diagnosis as well as follow-up. The development of MR angiography techniques now allows confirmation of the diagnosis of dural sinus occlusion. However, certain false-negatives may be observed with MRI, especially in the case of cortical vein thrombosis. When doubt persists concerning the diagnosis, cerebral angiography remains the reference examination.

Cerebral Angiography↗
PubMed1993

Treatment of recurrent malignant supratentorial gliomas with the association of procarbazine, thiotepa and vincristine: a phase II study.

Twenty patients previously treated with surgery, radiation therapy and chemotherapy with a nitrosourea for malignant supratentorial gliomas received a combination of procarbazine, thiotepa and vincristine (P.T.V.) at tumor recurrence. Procarbazine was given at a dose of 100 mg/m2 per os from day 1 (D1) to day 15 (D15), thiotepa was administered i.v. at a dose of 35-45 mg/m2 at D1, and vincristine at a dose of 1.4 mg/m2 at D1 and D8. Courses of therapy were repeated every four weeks. Tolerance was evaluated in 20 patients. Three patients developed peripheral neuropathy after 2 or 3 courses of vincristine which was then discontinued. Blood toxicity over grade I occurred in 8 patients (40%). One patient developed a grade i.v. pancytopenia. All 20 patients could be evaluated for therapeutic response. A partial response was noted in 3 patients (15%): 1 glioblastoma multiforme, 1 anaplastic oligodendroglioma and 1 anaplastic astrocytoma. In these three patients time to tumor progression was 10, 11+ and 5 months, respectively. Stabilization lasting 4 months was observed in one patient (anaplastic astrocytoma). Estimated median duration of survival for the entire group was 4.5 months following the onset of PTV (13 months following the date of histology).

Adult↗
PubMed1992

Expression of tissue factor pathway inhibitor by cultured endothelial cells in response to inflammatory mediators.

We recently proposed that endothelium may represent the primary physiologic site of synthesis of the tissue factor pathway inhibitor (TFPI). In support of this conclusion, we have now found that the poly(A)+ RNAs obtained from rabbit and bovine lung tissues contain abundant amounts of TFPI messenger RNAs (mRNAs), whereas the poly(A)+ RNAs obtained from the liver of these animals contain less than 5% of that found in the lung tissues. Because inflammatory mediators are known to upregulate tissue factor (TF) expression by the endothelium, we have examined the effect of these agents on the TFPI expression by the cultured endothelial cells. When cultured human umbilical vein endothelial cells were stimulated (in 10% fetal bovine serum) with phorbol myristate acetate (PMA), endotoxin, interleukin-1, or tumor necrosis factor-alpha, the TF mRNA increased approximately 7- to 10-fold within 2 to 4 hours. Unstimulated cells constitutively expressed TFPI mRNA and its levels either did not change or increased slightly (up to 1.5-fold) upon stimulation with these inflammatory agents. TF mRNA abruptly declined to a negligible level and the TFPI mRNA returned essentially to the basal level at approximately 24 hours. The membrane-bound TF clotting activity of induced cells peaked between 4 and 8 hours, and finally declined. The cumulative TFPI activity secreted into the media was either unchanged or slightly higher in the induced cell cultures as compared with that present in the noninduced cultures. Endothelial cells were also cultured in 10% heat-inactivated human serum derived from plasma or whole blood. TFPI secreted into the media containing whole blood serum was consistently higher (approximately 1.5-fold at 8 hours) than that secreted into the media supplemented with serum obtained from plasma lacking the formed elements; these cells also expressed similarly increased levels of TFPI mRNA. Moreover, PMA-stimulated cells cultured in whole blood serum expressed modestly increased levels of TFPI mRNA (approximately 1.5-fold); supernatants from these cells also contained similarly increased TFPI activity. Cumulatively, our data indicate that, unlike thrombomodulin and fibrinolytic enzymes synthesized by the endothelial cells, TFPI synthesis is not downregulated and may be slightly upregulated during an inflammatory response. Inspection of the 5' flanking region of the TFPI gene showed a conserved GATA-binding motif located approximately 400 bp upstream of the proposed transcription initiation site(s). This motif by binding to the GATA-2 transcriptional factor may keep the endothelium in an 'on' state for constitutive expression of TFPI.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Cerebral venous thrombosis.

Neuroimagining facilities allow early recognition of cerebral venous thrombosis (CVT), which now appears far more common than previously assumed. The diagnosis remains difficult because of a wide spectrum of clinical presentation and a highly variable mode of onset. Numerous conditions (presently mostly noninfectious) can cause or predispose to CVT, which therefore requires an extensive etiologic work-up. The functional and vital prognosis is much better than classically thought with, in noninfectious CVT, a fatality rate of less than 10% and a complete recovery in over 70%. Although spontaneous recovery is possible, the efficacy of heparin is now well established.

Anticoagulants↗
PubMed1991

Adenosine A1 and non-A1 receptors: intracellular analysis of the actions of adenosine agonists and antagonists in rat hippocampal neurons.

Adenosine and its agonists exert a depressant effect on neuronal activity by interacting with the adenosine A1 receptor. There is now also evidence for electrophysiological effects mediated by adenosine receptors other than the A1 type, possibly A2 receptors. A1 and A2 receptor-induced changes in the electrical properties of neuronal membranes were investigated by intracellularly recording from rat hippocampal CA1 neurons and using the adenosine agonists, 5'-N-ethylcarboxamidoadenosine (NECA) and R-phenylisopropyladenosine (PIA), and the unselective A1 and A2 receptor antagonist, theophylline and the selective A1 receptor antagonist, 8-cyclopenthyl-1,3-dipropylxanthine (DPCPX). PIA and NECA produced an inhibitory effect which was blocked by DPCPX and thus was mediated by A1 receptors. PIA produced inhibition at lower concentrations (0.1-1 mumol/l) than NECA (0.5-10 mumol/l), whereas at high concentrations (2.5 mumol/l) it exerted a dual effect, i.e. either an inhibitory or an excitatory one. During simultaneous perfusion with the A1 receptor antagonist DPCPX, PIA produced concentration-dependent excitatory effects at concentrations above 1 mumol/l. These excitatory effects were blocked by theophylline. DPCPX produced excitation that was enhanced by NECA. Forskolin caused no change in the membrane properties. It is concluded that (1) NECA and PIA affect the membrane properties not only by an action on the A1 but also on non-A1 receptors, because the excitatory effects of PIA and NECA were insensitive to DPCPX and abolished by theophylline; (2) PIA and NECA are more potent at A1 than at A2 receptors; (3) PIA is more potent than NECA at A1 and A2 receptors; (4) effects mediated by A2 receptors prevail over those mediated by A1 receptors when A2 receptors are activated; and (5) the non-A1 receptor-mediated effects are independent of an increased formation of cAMP.

Adenosine↗
PubMed1990

[Hyperthermic-antiblastic isolation perfusion for advanced melanoma of the limbs. The technic, immediate results and a review of the literature].

Hyperthermic antiblastic isolated perfusion is a method largely used for the treatment of locally advanced limb melanoma. The method requires vascular isolation and hyperthermic perfusion of the limb using an extracorporeal circuit and administering the melphalan as antiblastic drug. Twenty-six patients with primary or recurrent melanoma of the limbs have undergone this treatment at our Institute. There were no cases of operative mortality and systemic toxicity was negligible. The local complications were transitory and no patient showed symptoms of nervous toxicity or permanent functional damage. Two cases of deep thrombophlebitis and two of lymphocele were documented a few months after treatment. Four clinically complete responses, 3 partial and 2 cases of stable disease were observed in the 9 patients treated with unexcised lesions. Our data like the totality of the present experience points to the safety of this method in the therapy of locally advanced limb melanoma. Nevertheless further controlled studies are required to define its role in order to improve survival.

Adult↗
PubMed1990

The low KM-phosphodiesterase inhibitor denbufylline enhances neuronal excitability in guinea pig hippocampus in vitro.

The actions of the phosphodiesterase inhibitor denbufylline on the excitability of hippocampal neurons were investigated by means of extracellular and intracellular recordings. Denbufylline, which has been shown to selectively inhibit a low KM, Ca2+/calmodulin-independent phosphodiesterase isozyme, concentration-dependently increased the amplitude of the extracellularly recorded CA1 population spike evoked by electrical stimulation of the Schaffer collateral/commissural pathway. Concentration-response-curves yielded an EC50 for denbufylline of 0.76 microM. In comparison, the non-selective phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) also produced an increase in the amplitude of the population spike. From the concentration-response-curve, which was steeper than that of denbufylline, an EC50 for IBMX of 1.04 microM was obtained. However, despite their similar EC50 values, denbufylline was found to be significantly more potent at lower concentrations (less than or equal to 300 nM) than IBMX. Intracellular recordings from CA1 pyramidal cells revealed postsynaptic actions of denbufylline (300 nM) as indicated by a small drug-induced depolarization (2-5 mV) associated with an increase in membrane input resistance by 10-20%. In addition, denbufylline blocked the accommodation of trains of action potentials evoked by the injection of depolarizing current pulses. The results suggest i) that accumulation of adenosine-3',5'-monophosphate (cAMP) in the postsynaptic cell and/or in the presynaptic terminal produced by blockade of phosphodiesterases leads to enhanced synaptic transmission in the CA1 area of the hippocampus and ii) that a low KM, Ca2+/calmodulin-independent cAMP-phosphodiesterase is an important component involved in the regulation of the intracellular cAMP level at synapses of central nervous system neurons.

1-Methyl-3-isobutylxanthine↗
PubMedDate not supplied

Comparison of plasma and leukocyte vitamin C status between asthmatic and healthy subjects.

In a case-control study the vitamin C status of 50 adults with chronic controlled asthma was compared with that of 50 randomly selected healthy controls. Vitamin C intake was assessed by 3-day dietary recall, and plasma and leukocyte vitamin C concentrations were measured colorimetrically. A positive significant correlation was found between plasma vitamin C and dietary vitamin C intake. Plasma and leukocyte vitamin C levels were significantly lower in the asthma group. Plasma vitamin C was deficient (< 0.4 mg/dL) in significantly more patients than controls (38.0% versus 0%) and leukocyte vitamin C (< 20 microg/10(8) leukocytes) was deficient in 92.0% of asthmatics versus 8.0% of controls. A significant association was observed between duration of asthma and plasma vitamin C level.

Adult↗