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Biomedical subjects

C Argentino

Publications and source records attributed to C Argentino.

At least 19 recordsLinked to original sources
PubMed2005

Prognostic significance of admission levels of troponin I in patients with acute ischaemic stroke.

OBJECTIVES: Successful prediction of cardiac complications early in the course of acute ischaemic stroke could have an impact on the clinical management. Markers of myocardial injury on admission deserve investigation as potential predictors of poor outcome from stroke. METHODS: We prospectively investigated 330 consecutive patients with acute ischaemic stroke admitted to our emergency department based stroke unit. We analysed the association of baseline levels of cardiac troponin I (cTnI) with (a) all-cause mortality over a six month follow up, and (b) in-hospital death or major non-fatal cardiac event (angina, myocardial infarction, or heart failure). RESULTS: cTnI levels on admission were normal (lower than 0.10 ng/ml) in 277 patients (83.9%), low positive (0.10-0.39 ng/ml) in 35 (10.6%), and high positive (0.40 ng/ml or higher) in 18 (5.5%). Six month survival decreased significantly across the three groups (p<0.0001, log rank test for trend). On multivariate analysis, cTnI level was an independent predictor of mortality (low positive cTnI, hazard ratio (HR) 2.14; 95% CI 1.13 to 4.05; p = 0.01; and high positive cTnI, HR 2.47; 95% CI 1.22 to 5.02; p = 0.01), together with age and stroke severity. cTnI also predicted a higher risk of the combined endpoint "in-hospital death or non-fatal cardiac event". Neither the adjustment for other potential confounders nor the adjustment for ECG changes and levels of CK-MB and myoglobin on admission altered these results. CONCLUSIONS: cTnI positivity on admission is an independent prognostic predictor in acute ischaemic stroke. Whether further evaluation and treatment of cTnI positive patients can reduce cardiac morbidity and mortality should be the focus of future research.

Acute Disease↗
PubMed2003

Emergency and early carotid endarterectomy in patients with acute ischemic stroke selected with a predefined protocol. A prospective pilot study.

AIM: The appropriateness of early carotid endarterectomy (CEA) in patients with acute ischemic stroke is still unsettled. The aim of this study was to verify the safety and feasibility of early CEA in a consecutive series of patients with acute ischemic stroke observed in an emergency Department Stroke Unit. METHODS: During a 24-month study, out of 756 patients with acute ischemic stroke 33 (4.4%) were scheduled for early CEA. Endarterectomy procedures were distinguished according to the time between the onset of stroke and operation as emergency (within 8 hours), early CEA (1-18 days). Patients with impaired consciousness or an infarct larger than 2.5 cm on computed tomographic (CT) or magnetic resonance (MR) scans or both were excluded from surgery. All patients underwent spiral CT, echo-color-Doppler (ECD) sonography, transcranial Doppler (TCD) sonography and, when necessary, MR angiography within 6 hours of admission. No patient underwent conventional angiography. Most patients were operated on under cervical block (CB) anesthesia; general anesthesia (GA) was used only for those with an unstable neurological deficit. Selective shunting was used on the basis of intra-operative transcranial Doppler in patients under GA and the onset or worsening of neurological deficit under CB anesthesia. RESULTS: Of the 6 patients operated on within a median 6 hours after the onset of stroke, 1 (16.5%) had a fatal hemorrhagic transformation of the infarct, while the remaining 5 (83.5%) stopped fluctuating or progressing and had a favourable neurological outcome. Of the 16 patients operated on within a median 36 hours and of the 11 patients operated on within 7 days, none deteriorated after operation. CONCLUSION: Emergency CEA is feasible for acute ischaemic stroke provided that strict selection criteria are applied and the door-to-surgery interval is kept short (within 8 hours). Early CEA for secondary prevention is feasible and safe, confirming that a delayed operation is in most cases unwarranted. Large randomized trials are warranted before implementing emergent and early CEA in routine clinical practice.

Acute Disease↗
PubMed2001

Growth advantage of chronic myeloid leukemia CFU-GM in vitro: survival to growth factor deprivation, possibly related to autocrine stimulation, is a more common feature than hypersensitivity to GM-CSF/IL3 and is efficiently counteracted by retinoids +- alpha-interferon.

Bcr/abl fusion gene, in experimental models, induces survival to growth factor deprivation and hypersensitivity to IL3. However, conflicting data were reported about chronic myeloid leukemia (CML) progenitors. We investigated the responsiveness of purified CML CFU-GM to GM-CSF/IL3 and their survival to growth factor deprivation. CFU-GM hypersensitivity to IL3 and/or GM-CSF was found in 3/11 CML cases only. CML CFU-GM survived well in stroma-free 'mass' culture (5 x 10(4) cells/ml) without cytokine addition, up to day 11, average recovery being around 95% in medium + 10% fetal bovine serum and 67-81% in serum-free medium. Conversely, normal progenitors declined steadily, particularly after extensive purification (18 +/- 10% recovery at the 7th day), and in serum-free medium (4 +/- 6% recovery). By contrast, normal and CML CFU-GM declined in a similar way in limiting dilution cultures (1-10 cells/50 microl). We also investigated the effects of retinoic acid and alpha-interferon on CFU-GM survival. Both all-trans- and 13-cis retinoic acid, particularly in combination with alpha-interferon, reduced CML CFU-GM recovery down to normal progenitors' values. In conclusion, hypersensitivity to CSFs is rare in CML, whereas resistance to growth factor deprivation has been confirmed in mass, but not in limiting, dilution cultures. Both stereoisomers of retinoic acid, at therapeutic concentrations and in combination with alpha-interferon, can overcome the survival advantage of CML progenitors.

Cell Division↗
PubMed2001

Treatment of cerebrovascular diseases: state of the art and perspectives.

Ischaemic penumbra is defined as the area of brain tissue that maintains some blood flow following ischaemic accident. This zone may be rescued by both neuroprotection and arterial revascularization. Early thrombolysis has been used with encouraging results since 1995 in several trials testing both streptokinase and recombinant tissue plasminogen activator (r-TPA): the r-TPA results are definitely more positive than those of streptokinase, despite an increased incidence of symptomatic haemorrhagic transformation, r-TPA significantly reducing death or dependency at the end of follow-up. Despite the fact that some experimental periods of application of these therapeutic strategies demonstrated real cost-effective benefits, only 1% of patients reaching hospital in time for thrombolysis are currently treated. This is because the profile of patients at risk of haemorrhagic transformation, which is definitely the most feared side-effect of thrombolysis in stroke, is yet to be clearly defined. Extended computerized tomography (CT) signs of the index stroke have been repeatedly indicated as reliable predictors of haemorrhagic transformation even if currently there are significant discrepancies in the criteria adopted by different researchers to define early CT signs. Based on experimental ischaemia, strategies for protecting the basal lamina during thrombolysis are suggested: neuroprotection is the second approach to stroke therapy; pharmacological reperfusion and brain protection are probably mutually dependent.

Cerebrovascular Disorders↗
PubMed2001

Relationship between vascular enhancement, cerebral hemodynamics, and MR angiography in cases of acute stroke.

BACKGROUND AND PURPOSE: The use of MR angiography and contrast-enhanced T1-weighted MR imaging in cases of acute cerebral ischemia may be helpful in the evaluation of middle cerebral artery (MCA) occlusion and leptomeningeal collaterals, respectively. The aim of our work was to investigate the relationship between MCA occlusion, T1-weighted vascular contrast enhancement, hemodynamic alterations, and tissue damage in cases of acute ischemic stroke. METHODS: We studied the MCA territory in 15 patients with acute ischemic stroke within 8 hr of symptom onset. The first MR imaging study (<8 hr after onset) comprised diffusion-weighted imaging, MR angiography, perfusion-weighted imaging, and contrast-enhanced T1-weighted MR imaging sequences. Follow-up MR imaging, performed 1 week later, consisted of MR angiography and T2-weighted fluid-attenuated inversion recovery MR imaging. RESULTS: Early MR angiography showed MCA stem occlusion in nine of 15 patients. Patients with MCA occlusion had significantly larger areas of abnormality on early diffusion-weighted images, significantly larger areas of altered hemodynamics, larger final lesion volumes, and poorer clinical outcome. Among the nine patients with MCA stem occlusion, vascular enhancement was marked in seven and absent in two who had complete MCA infarcts and poor clinical outcome. Among patients with MCA patency, vascular enhancement was marked in only one, mild in four, and absent in one. Patients with marked vascular enhancement had significantly larger regions of altered hemodynamics and significantly higher asymmetries in both regional cerebral blood volume and mean transit time because of increased values in the affected hemisphere. CONCLUSION: Among patients with stroke with MCA occlusion, marked vascular enhancement and increased blood volume indicate efficient leptomeningeal collaterals and compensatory hemodynamic mechanisms.

Aged↗
PubMed2000

Computed tomography findings in the first few hours of ischemic stroke: implications for the clinician.

In order to evaluate the clinical usefulness of emergency computed tomography (CT) in acute ischemic stroke, we assessed whether CT findings within the first few hours of stroke onset reliably predict type, site and size of the index infarction, and risk of death or disability. For this reason we reviewed clinical and CT findings in a cohort of unselected consecutive patients referred to the stroke unit of a large urban hospital because of a presumed ischemic stroke in the anterior circulation (AC), and submitted to CT within 5 h from onset. Out of 158 total patients, emergency CT revealed parenchymal changes compatible with AC focal ischemia in 77 (49%) and a hyperdense middle cerebral artery (MCA) in 41 (26%). Parenchymal changes and hyperdense MCA predicted an AC territorial infarction respectively in 97% of cases (95% C.I. 93% to 100%) and in 95% of cases (95% C.I. 88% to 100%). Site and size of early changes coincided with those of final lesions in 79% of patients with cortical changes and in 95% of patients with cortico-subcortical changes, but only in 37% of patients with initial subcortical changes, the remainder of whom developed a cortico-subcortical infarction. At logistic regression parenchymal changes were the only independent predictor of an AC territorial infarction. Negative predictive power, however, was only 40% (95% C. I. 29% to 51%) for parenchymal changes, and 35% for hyperdense MCA (95% C.I. 26% to 44%). The odds for death or disability at 1 month associated with parenchymal changes were thrice as high as with negative CT, even after adjustment for clinical severity on admission. These results indicate that CT scan adds significantly to the prediction of outcome made on clinical grounds. The frequent development of a territorial infarction in patients with initially negative CT and the subsequent recruitment of the cortex in those initially exhibiting only subcortical changes suggest that the transition from ischemia to infarction often occurs after the first five h following stroke.

Adult↗
PubMed2000

Overweight as an adverse prognostic factor for non-Hodgkin's lymphoma patients receiving high-dose chemotherapy and autograft.

Despite detailed evaluation of disease-associated prognostic factors, little is known about the impact of overweight in autograft programs for non-Hodgkin's lymphoma (NHL) patients. In order to address this issue, 121 NHL patients were retrospectively evaluated. They had been upfront (92 patients) or in relapse (29 patients) and received high-dose sequential (HDS) chemotherapy including peripheral blood progenitor cell (PBPC) autograft. Body mass index (BMI) was calculated as weight in kilograms divided by the square of the height in meters; overweight was defined as BMI > or = 28. Univariate and multivariate analyses were used to determine the prognostic implication of overweight and other known prognostic indicators on overall (OS) and event-free (EFS) survival for the entire group and overweight and non-overweight (reference) subgroups. With a median follow-up of 3 years, the estimated 5-year OS and EFS for the entire group were 58% and 49%, respectively. Twenty-eight patients (23%) had BMI > or = 28. Their median OS and EFS were 2.2 and 1.4 years, respectively, whereas median OS and EFS for the reference group have not been reached, with a 5-year projection of 65 and 55%, respectively (P < 0.002). On multivariate analysis, the risk of death among overweight patients was 2.9 (CI, 1.3-6.2) times that of the reference group; using EFS as the end point, a similar association between overweight and survival was observed. In conclusion, in high-risk NHL patients undergoing intensive chemotherapy and PBPC autografting overweight is associated with a poorer outcome.

Adult↗
PubMed1999

Dose-intensive melphalan with stem cell support (MEL100) is superior to standard treatment in elderly myeloma patients.

A clinical relationship between dose-intensity of melphalan and response rate has been demonstrated in multiple myeloma. Promising results have been reported after 200 mg/m(2) melphalan, especially in younger patients. It is uncertain whether 100 mg/m(2) melphalan (MEL100) can offer similar results in older patients. To address this issue, patients were treated with 2 or 3 MEL100 courses followed by stem cell support. Seventy-one patients (median age, 64 years) entered the protocol at diagnosis. Their clinical outcome was compared with that of 71 pair mates (median age, 64 years) selected from patients treated at diagnosis with oral melphalan and prednisone (MP) and matched for age and beta2-microglobulin. Complete remission was 47% after MEL100 and 5% after MP. Median event-free survival was 34 months in the MEL100 group and 17.7 months in the MP group (P <.001). Median overall survival was 56+ months for MEL100 and 48 months for MP (P <.01). In a multivariate analysis, beta2-microglobulin levels and MEL100 were independent risk factors associated with outcome: superior event-free and overall survival were observed in patients presenting low beta2-microglobulin levels at diagnosis and receiving MEL100 as induction regimen. In conclusion, MEL100 was superior to MP in terms of complete remission rate, event-free survival, and overall survival.

Aged↗
PubMed1999

An analysis of which subgroups of multiple myeloma patients, divided according to b(2)-microglobulin and plasma cell labeling index, benefit from high dose vs conventional chemotherapy.

BACKGROUND AND OBJECTIVE: The clinical advantage of high-dose therapy (HDT) over standard treatment for multiple myeloma (MM) patients has been recently assessed. Which patient subgroups benefit most from this approach is unclear. DESIGN AND METHODS: To address this issue, the outcome of 54 patients under 55 years old treated with HDT was compared with that of 101 age-matched controls selected from 390 patients who received standard melphalan and prednisone (MP) chemotherapy in a national multi-center trial (M90 protocol). RESULTS: The complete response (CR) rate was 50% in the HDT group compared to 5% in the MP group. Event-free survival (EFS) was three times longer for the HDT patients (median 34.5 vs 12.2 months, p<0. 0001), though the controls enjoyed a prolonged survival after relapse, and hence there was no statistically significant difference in OS. Overall survival (OS) was analyzed in relation to to two major prognostic factors: b(2)-microglobulin (b(2)-M) and bone marrow plasma cell labeling index (LI). HDT significantly improved OS in poor prognosis patients with a high LI (>1.2%), (median 49.5 vs 32.5 months, p<0.03), whereas it did not prolong OS in poor prognosis patients with high b(2 )-M (> 3 mg/L). INTERPRETATION AND CONCLUSIONS: In conclusion, HDT has a major impact on CR and EFS, and is the treatment of choice for patients with a high LI. Alternative strategies should be adopted in poor prognosis patients with high b(2 )-M.

Antineoplastic Agents↗
PubMed1998

Early spontaneous improvement and deterioration of ischemic stroke patients. A serial study with transcranial Doppler ultrasonography.

BACKGROUND AND PURPOSE: The purpose of our study was to investigate whether emergency transcranial Doppler (TCD) findings and their modifications over the first 48 hours are related to early neurological changes in acute ischemic stroke patients. METHODS: Ninety-three patients underwent CT scan within 5 hours of a first-ever ischemic hemispheric stroke, and TCD serial examinations at 6, 24, and 48 hours after stroke onset. We classified TCD findings as follows: normal; middle cerebral artery (MCA) asymmetry (asymmetry index between affected and contralateral MCAs below -21%); and MCA no-flow (absence of flow signal from the affected MCA in the presence of ipsilateral anterior and posterior cerebral artery signals through the same acoustic window). We considered early deterioration and early improvement to be a decrease or an increase of 1 or more points, respectively, in the Canadian Neurological Scale score over the same period. RESULTS: At 6-hour TCD examination, MCA asymmetry and MCA no-flow were present in 6 (22%) and 2 (7%), respectively, of 27 improving patients; in 20 (43%) and 10 (22%) of 46 stable patients, and in 9 (45%) and 8 (40%) of 20 deteriorating patients. TCD findings were normal in the remaining patients (P = 0.001). At serial TCD, we detected early (within 24 hours) recanalization (from no-flow to asymmetry or normal and from asymmetry to normal) in 2 (25%) improving patients, in 7 (23%) stable patients, and in 5 (29%) deteriorating patients and late (between 24 and 48 hours) recanalization in 4 (50%) improving patients, in 6 (20%) stable patients, and in none of the deteriorating patients (P = 0.03, chi 2 for trend, improving versus nonimproving irrespective of the timing of recanalization). One deteriorating patient (5%) developed a non-flow from an initial MCA asymmetry. Logistic regression selected normal TCD (odds ratio [OR], 0.17; 95% confidence interval [CI], 0.06 to 0.46) as an independent predictor of early improvement and abnormal TCD (asymmetry plus no-flow) (OR, 5.02; 95% CI, 1.31 to 19.3) as an independent predictor of early deterioration. CONCLUSIONS: TCD examination within 6 hours after stroke can help to predict both early deterioration and early improvement. Serial TCD shows that propagation of arterial occlusion is rarely related to early deterioration, whereas the fact that it can detect early recanalization (within 24 hours) in deteriorating patients and both early and late recanalization (after 24 hours) in improving patients suggests the existence of individual time frames for tissue recovery.

Acute Disease↗
PubMed1997

Multiple myeloma: reduced plasma cell contamination in peripheral blood progenitor cell collections performed after repeated high-dose chemotherapy courses.

The possibility of reducing tumour cell contamination by cytotoxic drug courses prior to peripheral blood progenitor cell (PBPC) collection was evaluated in two consecutives groups of multiple myeloma (MM) patient candidates for autograft. All patients were at disease onset and received two VAD (vincristine, doxorubicin and dexamethasone) courses as initial debulking. In the first group (44 patients), mobilization and harvest were performed 'upfront', after a single cyclophosphamide (CY) administration of 4 g/m2; in the second group (17 patients), PBPC were collected at the end of a high-dose sequential chemotherapy programme, including: CY 5 g/m2, etoposide (VP16) 2 g/m2, a chemotherapy-free interval with three courses of high-dose dexamethasone, a final mobilizing CY at 7 g/m2. G-CSF was given following each high-dose cytotoxic drug. Cytofluorimetric analysis was performed to quantify progenitors (CD34+ cells) and plasma cells, identified by the high CD38 expression and/or CD38 and CD138 coexpression. Large amounts of PBPC were collected in either group (median harvested CD34+/kg: 15.8 x 10(6) and 13.4 x 10(6), respectively; P=0.9). Circulating plasma cells were significantly higher in patients mobilized 'upfront' compared to those who received the high-dose sequence (median peak values of CD38bright/microl: 39 and 10, respectively; P=0.02); a similar difference was observed in the amount of contaminating plasma cells in the harvest products (median CD38bright/kg: 7.4 x 10(6) and 1.3 x 10(6), respectively; P=0.02). The results demonstrate that an in vivo purging approach is feasible in myeloma patients through repeated high-dose chemotherapy courses; this may provide less-contaminated material suitable for further in vitro purging procedures.

Adult↗
PubMed1997

Conventional induction treatments do not influence overall survival in multiple myeloma.

A retrospective analysis was performed on two subsequent myeloma patient series treated with the same conventional induction treatments, melphalan and prednisone or alternating VMCP/VBAP: 273 were enrolled in the multicentre M83 trial (M83 trial group) from 1983 to 1986; 160 were referred to a single institution (Haemat. To group) from 1986 to 1994. Response to treatment was very similar in the two groups (53% v 50.3%). Remission duration curves merely overlapped (median 20 v 21 months). However, overall survival was significantly longer in the Haemat. To group (43.2 v 33 months, P < 0.04). This difference was due to a prolonged period from relapse or progression to death (21 v 8 months, P < 0.01; 20.8 v 7 months, P < 0.009). Prolonged survival was also observed in poor-prognosis patients with a serum beta2-microglobulin level > 3 mg/l, in the Haemat. To group (31.8 v 24.2 months, P < 0.04). The same induction treatments produced almost identical response rate and remission duration in both groups, but overall survival was 10 months longer for one group. However, it could be argued that treatment salvage modalities and support therapies have been improved in a decade. Lastly, induction treatments did not influence overall survival.

Adult↗
PubMed1997

Acute ischemic strokes improving during the first 48 hours of onset: predictability, outcome, and possible mechanisms. A comparison with early deteriorating strokes.

BACKGROUND AND PURPOSE: Our aims were to identify predictors of early neurological improvement in acute ischemic stroke patients, to evaluate its impact on clinical outcome, and to investigate possible mechanisms. METHODS: A consecutive series of 152 first-ever ischemic hemispheric stroke patients hospitalized within 5 hours of onset underwent a first CT scan within 1 hour of hospitalization, and the initial subset of 80 patients also underwent angiography. During the first 48 hours of hospital stay, an increase or a decrease of 1 or more points in the admission Canadian Neurological Scale (CNS) score was defined as early improvement or early deterioration, respectively. Repeated CT scan or autopsy was performed 5 to 9 days after stroke. RESULTS: Thirty-four patients (22%) improved, 84 (56%) remained stable, and 34 (22%) deteriorated. Logistic regression, which took into account vascular risk factors, baseline clinical and CT data, and therapies administered, selected younger age, lower admission CNS score, and absence of early hypodensity at first CT as independent predictors of early improvement. Among the patients who underwent angiography, logistic regression selected arterial patency and presence of collateral blood supply as independent predictors of early improvement. At the repeated CT scan or autopsy, improving patients presented the highest frequency of small infarcts. Thirty-day case-fatality rate and disability were lower in improving patients. Variables independently associated with outcome at logistic regression were admission CNS score, early deterioration, and early improvement. CONCLUSIONS: Early improvement can be predicted by the absence of early CT hypodensity and is highly predictive of good outcome. Presence of collateral blood supply and presumably early spontaneous recanalization are likely to be the mechanisms underlying early improvement.

Aged↗
PubMed1996

Thrombolysis acute ischemic stroke.

Thrombolysis is an attractive but potentially dangerous they for cerebral ischemia: it is capable of dissolving an arterial thrombus, but can also transform a pale infarct into a hematoma and/or may cause severe oedema and herniation. The safety and efficacy of the treatment critically depend on the timing of intervention ad on patient selection. In recent studies on ischemic stroke, spontaneous hemorrhagic transformation of an infarct seems to be related to the size of the lesion, and can be reliably predicted as early as five hours from stroke onset by the presence of focal hypodensity in the CT scan. That is why in the European Co-operative Acute Stroke (ECASS), a randomised, double blind trial on intravenous rt-PA in hemispheric stroke, patients showing, on the admission CT scan, extended early hypodensity, involving more than one third of the territory of the middle cerebral artery, were excluded from the day. Other ongoing trials on thrombolytic agents are expected to provide further indications on how to identify those patients most likely to benefit and least likely to experience adverse effects from this treatment.

Brain↗