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Biomedical subjects

S Paolucci

Publications and source records attributed to S Paolucci.

At least 37 records · Page 2Linked to original sources
PubMed2000

Early versus delayed inpatient stroke rehabilitation: a matched comparison conducted in Italy.

OBJECTIVE: To assess the specific influence of onset-admission interval (OAI) on rehabilitation results. DESIGN: A case-control study in consecutive stroke inpatients, enrolled in homogeneous subgroups, matched for age (within 1 year) and Barthel Index (BI) score at admission, and different for OAI to the rehabilitation ward. The short OAI group began rehabilitation treatment within the first 20 days from stroke, medium OAI group between days 21 and 40, and long OAI between days 41 and 60. SETTING: Rehabilitation hospital. PATIENTS: One hundred forty-five patients with sequelae of first stroke. MAIN OUTCOME MEASURES: Efficiency (average increase in BI per day), effectiveness (proportion of potential improvement achieved during rehabilitation) of treatment, and percentage of low- and high-response patients, calculated on BI, were evaluated. Odds ratios (ORs) of dropouts and of poor and excellent therapeutic response were also quantified. RESULTS: The short OAI subgroup had significantly higher effectiveness of treatment than did the medium (p < .05) and the long OAI groups (p < .005). Beginning treatment within the first 20 days was associated with a significantly high probability of excellent therapeutic response (OR = 6.11; 95% confidence interval [CI], 2.03-18.36), and beginning later was associated with a similar risk of poor response (OR = 5.18; 95% CI, 1.07-25.00). On the other hand, early intervention was associated with a five times greater risk of dropout than that of patients with delayed start of treatment (OR = 4.99; 95% CI, 1.38-18.03). The three subgroups were significantly (p < .05) different regarding the percentage of low and high responders. CONCLUSION: Our results showed a strong association between OAI and functional outcome.

Aged↗
PubMed2000

Quantification of the impact of HIV-1 reverse transcriptase and protease mutations on the efficacy of rescue HAART.

The reduction in the efficacy of rescue treatment (administered on a clinical basis) due to drug resistance was retrospectively quantified in 55 human immunodeficiency virus type 1 (HIV-1)-infected patients failing highly active antiretroviral therapy (HAART) by using a novel score calculation system based upon HIV-1 reverse transcriptase (RT) and protease (PR) mutations. Patients were all naive for nelfinavir (NFV) and efavirenz (EFV) and were assigned to one of the following rescue therapy schedules: (i) 17 patients received NFV + EFV + stavudine (d4T) (group A); (ii) 14 patients received NFV + saquinavir (SQV) + lamivudine (3TC) + d4T/zidovudine (AZT) (group B); (iii) 19 patients received NFV + d4T + didanosine (ddI)/3TC/zalcitabine (ddC) (group C); (iv) five patients received miscellaneous treatments including NFV (group D). Responders were considered patients showing a drop in HIV-1 RNA level > 0.5 log10 after 3 months of therapy. Forty-eight (28 responders and 20 non-responders) out of 55 patients completed the first 3 months of rescue therapy and reduction in HIV-1 viral load was found to be significantly higher in group A compared to groups B and C (81.2% responders vs. 38.5 and 40.0%, respectively). At baseline, no patient carried EFV- or d4T-resistant HIV-1 strains, despite prolonged administration of d4T, while 41/48 (87.2%) patients had mutations conferring resistance to NFV in the absence of previous treatment with this drug. A significant inverse correlation between reduction in viral load and reduction in therapy efficacy due to drug resistance, as determined by the score calculation system, was found (r = 0.62). A cut-off value of 36% reduction in therapy efficacy showed a positive predictive value (capacity to detect failure of rescue treatment) of 81.2% and a negative predictive value (ability to detect successful treatment) of 75.8%. In addition, 45 out of 48 patients completed also the 9-12 month period of rescue therapy and 10/28 responders had a rebound in HIV-1 viral load level detected after the first 3 months of rescue therapy. Of these, 5/7 (71.4%) showed a further reduction in rescue therapy efficacy due to the emergence of new mutations.

Anti-HIV Agents↗
PubMed2000

Cerebellar deficit and respiratory impairment: a strong association in multiple sclerosis?

The aim of the study was to analyse pulmonary function and to identify reliable prognostic factors associated with respiratory abnormalities in a consecutive series of patients with multiple sclerosis (MS). Pulmonary function was evaluated by means of a battery of measures, including maximal voluntary ventilation, forced vital capacity, forced expiratory volume, in 71 consecutive patients with primary and secondary progressive MS. Respiratory impairment was common in MS patients, occurring in 63.4% of all patients, ranging from 82.9% in non-ambulatory patients (with EDSS score >6.5) to 35.7% in ambulatory patients (with EDSS score <6). Severity of illness and cerebellar and mental impairment were significantly negatively associated with basal pulmonary function. Coordination plays an important role in determining respiratory abnormalities: respiratory abnormalities were found in 27 out of 32 patients (84.4%) with severe cerebellar impairment. The presence of severe cerebellar signs was associated with a very high risk of occurrence of respiratory impairment (O.R. = 6.24; 95% C.I. 1.71-22.82). Other significant variables were severity of illness (EDSS score > 6.5) (O.R. =4.71; 95% C.I. 1.42-15.66) and long disease duration (> 15 years) (O.R. = 3.39; 95% C.I. 1.01-11.42).

Analysis of Variance↗
PubMed1999

Efavirenz, nelfinavir, and stavudine rescue combination therapy in HIV-1-positive patients heavily pretreated with nucleoside analogues and protease inhibitors.

Tolerability, activity, and pharmacokinetic parameters of a combination therapy with efavirenz (EFV), nelfinavir (NFV), and stavudine (d4T) were evaluated in this study. Forty-seven HIV-1-infected study subjects, naive to NFV and nonnucleoside reverse transcriptase inhibitors (NNRTIs), who had experienced virologic failure while being treated with combination antiretroviral therapies including protease inhibitors (PIs), were enrolled. At baseline, HIV-1 viral load in plasma was 4.8 log10, CD4+ count was 204 cells/microl (both mean values); patients had received a mean of 3.1 different treatments (range, 2-5 treatments). Study medications were generally well tolerated; 7 of 47 patients (14.8%) were dropped from the study because of related drug toxicity. At week 24, mean plasma viral load (pVL) was reduced by 1.9 log10, with mean CD4+ count increased to 324 cells/microl (+/-59% from baseline); pVL was below the limit of detection (500 copies/ml) in 46.1% of patients. An extended follow-up study was performed at 12 months. Results showed a reduction of 1.7 log10 in pVL from basal values that was consistent with values observed at months 3 and 6. A history of previous use of PIs represented a negative prognostic marker. Sequencing analysis, performed in a subset of patients, showed the presence of multiple point mutations associated with PI resistance. Pharmacokinetic analysis demonstrated a marked interindividual variability in NFV plasma concentrations, producing in 4 of 18 patients (22%) trough concentrations lower than minimum effective concentration. In pretreated patients, further studies are needed to characterize the pharmacokinetic factors that affect response to therapy and the association of these results with the 95% inhibitory concentration (IC95) determined by phenotyping.

Adult↗
PubMed1999

Selective pressure exerted by immunodominant HIV-1-specific cytotoxic T lymphocyte responses during primary infection drives genetic variation restricted to the cognate epitope.

HIV-specific cytotoxic T lymphocytes (CTL) play a central role in the control of HIV-1 replication during primary infection. It has been hypothesized that the appearance of CTL escape mutants represents an important mechanism by which HIV-1 escapes the host cell-mediated immune response. However, evidences for a direct relationship between CTL responses and emergence of CTL escape mutants are still limited. Here we report detailed longitudinal analysis of DNA sequence variation performed over the entire HIV-1 envelope in two subjects during primary HIV infection. Estimates of the frequencies of synonymous (ds) and non-synonymous (dN) nucleotide substitutions were used to identify regions of the HIV-1 envelope which were subjected to significant levels of selective pressure. These regions were shown to comprise defined epitopes recognized by CTL. Furthermore, dN mutation fixed within these epitopes effectively abolished recognition by the host CTL response. These results provide compelling evidence that the CTL epitope mutations directly resulted from the selective pressure exerted by the virus-specific cytotoxic response.

Cells, Cultured↗
PubMed1999

Poststroke depression and its role in rehabilitation of inpatients.

OBJECTIVES: To identify the prevalence of poststroke depression (PSD) in a population of patients admitted for rehabilitation of neurologic sequelae of their first stroke, to recognize reliable prognostic factors associated with the occurrence of PSD, and to evaluate the impact of PSD on the results of rehabilitation treatment. METHODS: In a prospective study of 470 of 508 consecutive patients admitted to a rehabilitation hospital for sequelae of their first stroke, the relation between 23 independent variables and the development of depression was assessed by using a logistic regression analysis (forward stepwise). In addition, the impact of PSD on basal disability and on rehabilitation results was assessed by multiple measures (length of stay, efficiency, effectiveness, and percent of low responders on activities of daily living [ADL] and mobility). RESULTS: PSD occurred in 129 patients (27.4%). Being female and having more than 8 years of schooling were associated with a higher probability of developing depression (odds ratio [OR] = 1.94, 95% confidence interval [CI] = 1.27-2.96, and OR = 1.61, 95% CI = 1.04-2.48, respectively). No association was found with site or side of cerebral lesion. In a logistic model, depression was a significant independent predictor (OR = 1.99, 95% CI = 1.14-3.46) of low response on ADL in spite of treatment. CONCLUSIONS: PSD occurs especially in female patients and in patients with a high level of education and, even if treated, may affect rehabilitation results. No association was found between brain lesion location and PSD.

Activities of Daily Living↗
PubMed1999

Diagnostic and prognostic value of human cytomegalovirus load and IgM antibody in blood of congenitally infected newborns.

BACKGROUND: Diagnosis of congenital human cytomegalovirus (HCMV) infection relies on virus isolation from urine collected in the first 3 weeks of life. However, very little is known about the presence, levels and duration of HCMV pp65 antigenemia, viremia and DNAemia in congenitally infected newborns. OBJECTIVES: To investigate the diagnostic and prognostic value of HCMV load determination in blood of newborns/infants with congenital HCMV infection. STUDY DESIGN: HCMV pp65 antigenemia, viremia and DNAemia were investigated in 116 sequential peripheral blood leukocytes (PBL) samples from 41 newborns/infants with congenital HCMV infection and in 34 PBL samples from 34 uninfected newborn. Virus-specific IgM were determined in parallel on 145 sequential serum samples. RESULTS: Compared to virus isolation from urine, sensitivities of DNAemia, antigenemia, viremia, and IgM determination were 100, 42.5, 28.2, and 70.7%, respectively. Specificity was 100% for all assays. Antigenemia, viremia and DNAemia levels were significantly higher and persisted longer in newborns with symptomatic infection compared to subclinically infected babies, whereas no difference was observed for virus-specific IgM antibody between the two groups. CONCLUSIONS: (i) determination of viral DNA in blood at birth appears to be a sensitive and specific marker for diagnosis of congenital HCMV infection; (ii) significantly higher levels of HCMV load were detected in infants with symptomatic HCMV infection; and (iii) virus clearance from blood occurs spontaneously both in symptomatic and subclinically infected infants. However, the process takes longer in infants presenting with symptoms at birth.

Antigens, Viral↗
PubMed1998

Recovery of neglect after right hemispheric damage: H2(15)O positron emission tomographic activation study.

BACKGROUND: The neural correlates of recovery of unilateral neglect (ULN), as well as of other consequences of focal brain damage, are largely unknown. Functional neuroimaging methods (in particular, positron emission tomography [PET]) can be applied to the in vivo study of recovery mechanisms in neurologic patients. OBJECTIVE: To evaluate the functional cerebral correlates of recovery from ULN in patients with right-sided lesions, with the use of a PET activation paradigm. METHODS: Study of 3 patients with cerebrovascular lesions that involved corticosubcortical (patient 1) or subcortical (patients 2 and 3) areas of the right hemisphere. Unilateral neglect was tested twice, before and after completion of a 2-month rehabilitation program, after which all 3 patients showed considerable improvement. Similarly, 2 PET examinations were performed, before and after recovery, during the performance of a visuospatial task requiring the patients to detect and respond to visual targets moving on a computer screen from the right to the left visual hemifield (experimental condition). The cerebral activation was compared with a baseline task in which subjects responded to a black dot flashing in a fixed position of the right hemifield. RESULTS: The brain areas activated by the performance of the visuospatial task before and after recovery were compared. In all 3 patients, the regions notably more active after recovery were almost exclusively found in right-sided cortical areas and largely overlapped with those observed in a group of 4 normal subjects performing the same task. Other areas, which have been shown to be involved in attentional and oculomotor tasks in other PET studies, were also activated in patients with ULN. CONCLUSIONS: The behavioral recovery of ULN in these patients with predominantly subcortical lesions is mainly associated with cerebral activations in cortical regions similar to those observed in normal subjects. There is some evidence of functional reorganization in individual subjects, which involves other areas related to space representation and exploration.

Aged↗
PubMed1998

Post-stroke rehabilitation: an economic or medical priority? Current issues and prospects in light of new legislative regulations.

The aim of this study was to evaluate: 1) whether the reduction in duration of in-patient rehabilitation imposed by the Italian Ministry of Health's circular of 29/6/95 has been accompanied by a decline in the results achieved; and 2) whether the system of basing payments on diagnosis related group (DRG) criteria is capable of correctly evaluating differences in post-stroke clinical pictures. The study involved 461 of 497 patients consecutively admitted between 1991 and 1996 for rehabilitation after a first stroke. The average duration of hospitalisation for the period 1995-1996 was significantly shorter (p<0.001) than that of the previous years; at the same time, there was a significant increase (p<0.05) in the number of poor responders in both neurological and functional (mobility) terms. Furthermore, the early discharge after 60 days of the 1995-1996 patients compromised the stabilisation of recovery and led to a subsequent functional decline. It is therefore hoped that the current regulations will be revised and that payments based on a functional related group (FRG) criterion will be introduced.

Aged↗
PubMed1998

Changes in functional outcome in inpatient stroke rehabilitation resulting from new health policy regulations in Italy.

This study was designed to assess whether enforcement of new health policy regulations in Italy limiting fully paid hospital stay to 60 days has actually caused a decrease in rehabilitation outcomes of stroke patients. Final sample included 370 out of 398 consecutive patients hospitalized between 1993 and 1996 for first stroke sequelae. Rehabilitation results were compared between subgroups of patients admitted before and after new Italian regulations. Length of stay was significantly (p < 0.001) shorter in 1996 than in previous years. However, between 1993 and 1996 a significant (p < 0.05) decrease in effectiveness on mobility and a significant (p < 0.05) increase in "low responders" on both daily living activities and mobility was observed. Moreover, in 1995-96 the precocious discharge of patients compromised stabilization of recovery with subsequent functional worsening. After discharge, outpatient rehabilitation treatment was able to conserve achieved mobility status, but not functional status on daily living activities. We suggest revising the present regulation for medical rehabilitation services to one based on FRGs (functional related groups), so that the appropriate treatment can be carried out for each patient.

Journal Article↗
PubMed1998

CXCR4 and CCR5 genetic polymorphisms in long-term nonprogressive human immunodeficiency virus infection: lack of association with mutations other than CCR5-Delta32.

Polymorphisms in the coding sequences of CCR5 and CXCR4 were studied in a group of human immunodeficiency virus (HIV)-infected long-term nonprogressors. Two different point mutations were found in the CXCR4 coding sequence. One of these CXCR4 mutations was silent, and each was unique to two nonprogressors. The well-described 32-bp deletion within the CCR5 coding sequence (CCR5-Delta32) was found in 4 of 13 nonprogressors, and 12 different point mutations were found scattered over the CCR5 coding sequence from 8 nonprogressors. Most of the mutations created either silent or conservative changes in the predicted amino acid sequence: only one of these mutations was found in more than a single nonprogressor. All nonsilent mutations were tested in an HIV envelope-dependent fusion assay, and all functioned comparably to wild-type controls. Polymorphisms in the CXCR4 and CCR5 coding sequences other than CCR5-Delta32 do not appear to play a dominant mechanistic role in nonprogression among HIV-infected individuals.

Female↗
PubMed1998

Prognostic factors in rehabilitation of above knee amputees for vascular diseases.

PURPOSE: This study was undertaken to predict rehabilitation potential and prognostic factors of patients undergoing above knee amputation for vascular diseases. METHOD: In a prospective study on 144 patients consecutively admitted to our rehabilitation unit for above knee amputation, multiple regression analyses were used to assess the relationship between nine independent variables and a battery of outcome measures: the Rivermead Mobility Index (RMI) and Barthel Index (BI) effectiveness on discharge, length of hospital stay. Two multiple logistic regressions were performed, using as dependent variable the occurrence of good or partial autonomy in mobility, quantified as RMI scores. RESULTS: Advanced age was the most powerful prognostic factor influencing effectiveness expressed as both mobility (RMI) and BI. Patients aged < 65 years had a greater probability (odds ratio 2.92) of good autonomy in mobility than older patients. The absence of vascular impairment of the residual limb and timely admission to the rehabilitation hospital correlated positively with effectiveness of mobility. CONCLUSIONS: These findings indicate that relevant prognostic factors can be identified at the beginning of rehabilitation treatment.

Activities of Daily Living↗
PubMed1997

Evidence for rapid disappearance of initially expanded HIV-specific CD8+ T cell clones during primary HIV infection.

Down-regulation of the initial burst of viremia during primary HIV infection is thought to be mediated predominantly by HIV-specific cytotoxic T lymphocytes, and the appearance of this response is associated with major perturbations of the T cell receptor repertoire. Changes in the T cell receptor repertoire of virus-specific cytotoxic T lymphocytes were analyzed in patients with primary infection to understand the failure of the cellular immune response to control viral spread and replication. This analysis demonstrated that a significant number of HIV-specific T cell clones involved in the primary immune response rapidly disappeared. The disappearance was not the result of mutations in the virus epitopes recognized by these clones. Evidence is provided that phenomena such as high-dose tolerance or clonal exhaustion might be involved in the disappearance of these monoclonally expanded HIV-specific cytotoxic T cell clones. These findings should provide insights into how HIV, and possibly other viruses, elude the host immune response during primary infection.

Amino Acid Sequence↗
PubMed1997

Accumulation of human immunodeficiency virus-specific cytotoxic T lymphocytes away from the predominant site of virus replication during primary infection.

Down-regulation of the initial burst of viremia during primary human immunodeficiency virus (HIV) infection is thought to be mediated predominantly by HIV-specific CD8+ cytotoxic T lymphocytes (CTL). This response is associated with major perturbations in the T cell receptor (TCR) repertoire. To investigate the failure of the cellular immune response to adequately control viral spread and replication and to prevent establishment of HIV infection, changes in the TCR repertoire and in the distribution of virus-specific CTL between blood and lymph node were analyzed in three patients with primary infection. By the combined use of clonotype-specific polymerase chain reaction and analysis of the frequency of in vivo activated HIV-specific CTL, it was shown that HIV-specific CTL clones preferentially accumulated in blood as opposed to lymph node. Accumulation of HIV-specific CTL in blood occurred prior to effective down-regulation of virus replication in both blood and lymph node. These findings should provide new insights into how HIV, and possibly other viruses, elude the immune response of the host during primary infection.

Antigen Presentation↗
PubMed1997

Poststroke late seizures and their role in rehabilitation of inpatients.

PURPOSE: This study was designed to (a) identify the prevalence of poststroke late seizures in a population of patients admitted to rehabilitation of neurologic sequelae of their first stroke, (b) recognize reliable prognostic factors associated with the occurrence of poststroke late seizures, and (c) evaluate the impact of seizures on the results of rehabilitation treatment. METHODS: In a prospective study of 306 consecutive patients admitted to a rehabilitation hospital for sequelae of their first stroke, we assessed the relation among 15 independent variables and the development of seizures by using multiple regression analysis (forward stepwise). In addition, we evaluated the impact of occurrence of poststroke seizures on both efficiency and effectiveness of rehabilitation and length of stay. RESULTS: Poststroke late seizures occurred in 46 (15.03%) patients, with a mean interval from stroke of 101.98 +/- 37.96 days. In multiple regression analysis, putaminal and lobar hemorrhages showed a significant positive association with the development of seizures (p < 0.005), whereas high scores on the Canadian Neurological Scale (CNS) (indicating less severe strokes) and increasing age were negatively associated (p < 0.01 and p < 0.05, respectively). Patients with putaminal and lobar hemorrhages and patients with severe stroke (CNS score at admission, <7) were at significantly greater relative risk of seizures [relative risk (RR) = 1.99, 95% confidence interval (CI), 1.11-1.39; RR = 3.00, CI, 1.06-1.13; and RR = 2.41, CI, 1.01-1.27, respectively). No significant association was found between poststroke seizures and results of rehabilitation. CONCLUSIONS: Poststroke late seizures occurred mainly in patients with putaminal and lobar hemorrhagic strokes but, if treated, did not affect rehabilitation therapy.

Aged↗
PubMed1996

Facilitatory effect of neglect rehabilitation on the recovery of left hemiplegic stroke patients: a cross-over study.

A study of the effect of specific training for visual neglect on the recovery of motor and functional impairment in stroke patients is reported. Two groups of right hemisphere stroke patients with hemispatial neglect and one group without neglect were assessed by means of three functional and neurological scales (Rivermead Mobility Index, Barthel Index, Canadian Neurological Scale). Three evaluations were made at 0, 2 and 4 months from the beginning of physical rehabilitation. During the first 2 months of physical rehabilitation one of the two groups of neglect patients was randomly assigned to specific training for neglect, and the second group to a general cognitive intervention; during the final 2 months of rehabilitation the types of training were switched in the two groups. The non-neglect patients improved steadily during physical rehabilitation. In contrast, the functional recovery of the two neglect groups was time-locked to the period of the specific training for neglect. At the time of admission, the two neglect groups performed at the same level; after 2 months of rehabilitation, the group with neglect training showed higher functional recovery than the group with only general cognitive intervention. When the latter group received neglect training, there was no longer any difference between the two neglect groups. This pattern was present for both of the functional scales used but not for the neurological scale. Motor and functional recovery of stroke patients with neglect seems to be significantly improved by the simultaneous presence of a treatment specifically focused on neglect.

Cerebrovascular Disorders↗
PubMed1996

Asymmetry of rapid eye movements in chronic unilateral neglect does not change with behavioral improvement induced by rehabilitation treatment.

A strong reduction of leftward rapid eye movements (REMs) during REM sleep was recently documented in patients with severe and chronic left unilateral neglect. The aim of the present research was to study the stability of the unilateral suppression of REMs before and after a rehabilitative treatment for neglect disorders. Six right-brain-damaged patients were tested for neglect at the beginning and at the end of a 2 month cognitive rehabilitation treatment. REMs were recorded during 1 night of undisturbed sleep before and after the training. Five out of 6 patients improved considerably their ability to attend the previously neglected left hemispace; in all patients REM asymmetry remained unchanged. The lack of relationship between the improvement of the neglect disorder and the persistence of REM asymmetry suggests that the sensorimotor mechanisms activated by rehabilitation are different from those involved in the production of REMs. It is proposed that: (a) the directional vectors of REMs are computed on the basis of the exclusive or predominant endogenous activation of the central attentional mechanisms related to vestibular input; (b) the presence of rightward and leftward saccades and the positive effects of the rehabilitation treatment are functionally linked to attentional oculomotor mechanisms that are not active in REM sleep.

Aged↗