Filippo Palermo

The impact of outpatient rehabilitation on quality of life in multiple sclerosis

Abstract It is well accepted that rehabilitative treatment can be effective in reducing disability and optimizing quality of life (QoL) of people with multiple sclerosis (MS). The aim of this study was to evaluate the effects of a comprehensive outpatient rehabilitative treatment on QoL in patients suffering from MS. We selected 111 patients from a sample of 407 patients who had consecutively entered the MS Center of Catania (which is located in southern Italy) in 1998. Fifty-eight were randomly assigned to the study treatment and 53 to a waiting list (control treatment). Kurtzkes EDSS and quality of Life (QoL)were the primary endpoints. QoL was measured with the generic multi-item SF-36 scales. We also used: the Beck Depression Inventory (BDI) for depression, the Tempelaar Social Experience Check-list (SET) for social activities and the Fatigue Impact Scale (FIS).The study treatment group was treated for 6 consecutive weeks, 6 days a week with a comprehensive rehabilitative outpatient model. The control treatment group was in a waiting list and was trained to self-exercises at home.EDSS remained unchanged in both groups. All health related QoL domains significantly improved in the study treatment (p < 0.001 in physical functioning, role physical, bodily pain, general health, and social functioning; p < 0.05 in vitality, role emotional and mental health).FIS, SET and BDI also improved significantly after the rehabilitative treatment in the study group (p < 0.001).The results of this study confirm the effectiveness of a short comprehensive outpatient model of rehabilitative treatment in people with MS and in particular in their QoL.

Slower Progression of HIV-1 Infection in Persons with GB Virus C Co-Infection Correlates with an Intact T-Helper 1 Cytokine Profile

Context Patients infected with HIV-1 progress to AIDS more slowly if they are co-infected with hepatitis G virus, also called GB virus C (GBV-C), than if they are not. The mechanism of this effect of GBV-C infection is not known. Contribution Among 80 asymptomatic HIV-1infected patients, T-helper 1 cytokine profiles changed unfavorably in those without GBV-C infection and remained stable in those with GBV-C infection. Implications Co-infection with GBV-C may slow progression of HIV-1 infection through a mechanism related to T-helper 1 cytokines. The Editors Hepatitis G virus, also called GB virus C (GBV-C), is a recently identified RNA virus belonging to the Flaviviridae family (1, 2). It is usually transmitted parenterally (2, 3). The prevalence of GBV-C viremia ranges from 20% to 24% among persons who use intravenous drugs (4, 5). Higher rates have been seen in patients with HIV-1 infection, regardless of intravenous drug use (4, 6). In recent surveys, HIV-1infected persons with GBV-C co-infection had better AIDS-free survival rates and higher CD4+ cell counts than HIV-1infected patients who were GBV-C negative (7-10). It has also been shown that GBV-C inhibits HIV-1 replication in vitro (11). Our objective was to evaluate AIDS-free survival rates, plasma HIV-1 viral load, and selected immunologic variables in 80 HIV-1seropositive patients with and without GBV-C co-infection. We sought to determine possible immunologic mechanisms involved in these co-infection scenarios. Methods The study was initiated between January and March 1989 at the Institute of Infectious Diseases, University of Catania, Catania, Italy. Institutional review boards at the Institute of Infectious Diseases, University of Catania, approved the follow-up protocol. Signed informed consent was obtained from each patient. Among 319 HIV-1seropositive patients, 240 used intravenous drugs, 60 were homosexual men, and 19 had received many blood transfusions. Eighty of these 319 patients (25%), all of whom used intravenous drugs, were asymptomatic and were enrolled in a prospective follow-up study to evaluate the progression of HIV-1related disease. All 80 patients underwent physical examination and routine blood biochemistry examinations every 6 months. Blood samples were obtained annually from each patient, and serum was stored at 80 C until use. The analyses for the current study were begun in January 1997. Quantitative plasma HIV-1 RNA levels and circulating levels of specific interleukins (ILs)IL-2, IL-4, IL-10, and IL-12were retrospectively determined in all serum samples. We determined GBV-C RNA levels in all serum specimens collected at the beginning of the study and at the end of follow-up. Analyses were repeated in January 2001. Anti-E2 antibodies were detected by using the Enzymun-Test Anti-HGenv (Boehringer Mannheim Corp., Indianapolis, Indiana). Plasma HIV-1 RNA copy numbers were determined by using the nucleic acid sequence-based amplification method (NASBA, Organon Teknika, Boxtel, the Netherlands). The sensitivity limit of the assay was 400 copies/mL. Interleukin-2 was analyzed by using a quantitative enzyme immunoassay (Predicta, Genzyme Diagnostics, Cambridge, Massachusetts) with a sensitivity limit of 4 pg/mL. Interleukin-4 was tested by using a quantitative enzyme immunoassay (InterTest, Genzyme Diagnostics) with a sensitivity limit of 0.045 ng/mL. Interleukin-10 was measured by using a competitive enzyme immunoassay (Cytokit Red 10, Genzyme Diagnostics), which had a range of detection between 0.195 and 200 ng/mL. Interleukin-12 levels were determined by using an enzyme immunoassay provided by R&D Systems (Oxon, United Kingdom) that had a lower sensitivity limit of 5 pg/mL. We measured GBV-C RNA level by using reverse transcriptase polymerase chain reaction, as described elsewhere (12). Statistical Analysis Plasma HIV-1 RNA levels were logarithmically transformed to normalize their distribution. Categorical variables were analyzed by using the Fisher exact test. The group means were compared by using the Student t-test. Variations of all interim values of plasma HIV-1 RNA level, CD4+ cell count, and IL levels were analyzed within each group by using two-way analysis of variance. We compared GBV-C RNApositive and GBV-C RNAnegative groups by using the MannWhitney U test to examine percentage variations from baseline values to values at the end of follow-up. Curves reflecting variations by time in immunologic and virologic variables were compared by using univariate repeated-measures analysis that followed an analysis-of-variance structure (13). Progression to AIDS was defined as the development of an opportunistic infection or malignant condition. We used the Kaplan-Meier method to evaluate the effect of GBV-C infection on AIDS-free survival by assuming that GBV-C and HIV-1 infection status was fixed at the beginning of follow-up. A P value less than 0.05 was considered statistically significant. Statistical analyses were performed by using SAS software, version 6.12 (SAS Institute, Inc., Cary, North Carolina). Role of the Funding Sources The funding sources had no direct control over the analysis of the study. Results The mean age of the study patients (SD) was 24.6 2.2 years. Fifty-two patients were men, and 28 were women. Mean duration of intravenous drug use (SD) was 24.2 1.8 months, and mean duration of known HIV-1 seropositivity (SD) was 9.2 1.6 months. The mean baseline CD4+ cell count (SD) was 471 55 109 cells/L. Fifty-eight patients declined to take any antiretroviral drug, and 6 were treated with zidovudine alone throughout the follow-up period. In 16 patients, didanosine was added to zidovudine, starting in 1993. In January 1997, follow-up was interrupted and all 80 patients began to receive different highly active antiretroviral therapy (HAART). At this time, 6 patients were asymptomatic, 24 had stage B disease, and 50 had stage C disease, according to stages defined by the U.S. Centers for Disease Control and Prevention. At the end of follow-up, the mean CD4+ cell count (SD) was 77 33 109 cells/L. Seventeen of the 80 serum specimens collected at the beginning of follow-up (21%) were positive for GBV-C RNA. All of these 17 patients maintained GBV-C viremia to the end of the follow-up period, and none of the 63 patients who were GBV-C RNA negative acquired the infection. Patients who were GBV-C negative and those who were GBV-C positive did not significantly differ in age, sex, duration of intravenous drug use and HIV-1 seropositivity, or rate of hepatitis C virus and hepatitis B virus infection (Table). Table. Epidemiologic and Virologic Variables Measured at Baseline and at the End of Follow-up Clinical Outcomes At the end of the 8-year follow-up, 3 of 17 GBV-Cpositive patients (18%) remained asymptomatic (stage A), 7 (41%) had stage B disease, and 7 (41%) had stage C disease. In the 7 patients with stage C disease, the following AIDS-defining diseases were observed: AIDS dementia complex (n = 7 [100%]), Pneumocystis carinii pneumonia (n = 4 [57%]), esophageal candidiasis (n = 3 [43%]), and Toxoplasma encephalitis infection (n = 1 [14%]). Three of 63 GBV-C RNAnegative patients (5%) had stage A disease, 17 (27%) had stage B disease, and 43 (68%) had stage C disease. Among those with stage C disease, the following diseases were observed: P. carinii pneumonia (n = 18 [42%]), esophageal candidiasis (n = 11 [26%]), Toxoplasma encephalitis infection (n = 5 [12%]), cryptococcal meningitis (n = 4 [9%]), intestinal cryptosporidiosis (n = 3 [7%]), Kaposi sarcoma (n = 2 [5%]), AIDS dementia complex (n = 2 [5%]), and disseminated cytomegalovirus disease (n = 1 [2%]). According to Kaplan-Meier curves showing progression to AIDS in HIV-1infected persons, cumulative AIDS-free survival rates at 24 and 48 months, respectively, were 0.5 (95% CI, 0.3 to 0.6) and 0.4 (CI, 0.3 to 0.5) in the GBV-Cnegative group and 0.9 (CI, 0.7 to 1.0) and 0.7 (CI, 0.5 to 0.9) in the GBV-Cpositive group (P = 0.02 for between-group comparisons). Mean AIDS-free survival time was 73 months (CI, 59 to 87 months) among GBV-Cpositive persons and 45 months (CI, 35 to 54 months) among GBV-Cnegative persons. Immunologic and Virologic Evaluations The Figure shows the cross-sectional averages of IL levels, CD4+ cell counts, and HIV RNA levels during the follow-up period. Annual plasma HIV-1 RNA levels significantly increased during follow-up in both the GBV-Cnegative and GBV-Cpositive groups, whereas CD4+ cell counts significantly decreased (P < 0.01 for all comparisons). In the GBV-Cnegative group, IL-4 and IL-10 levels increased significantly from baseline (P = 0.01 and P = 0.004, respectively) but IL-2 and IL-12 concentrations decreased significantly throughout the entire follow-up period (P = 0.005 and P = 0.01, respectively). In contrast, in the GBV-Cpositive group, none of the measured cytokine levels changed significantly during follow-up. The Table shows the percentage variation from baseline to the end of follow-up in plasma HIV-1 RNA levels, CD4+ cell counts, and cytokine concentrations between the two groups. Figure. Cross-sectional averages of interleukin ( IL ) levels, CD4+ cell counts, and HIV-1 RNA levels in GB virus C ( GBV-C )-positive and GBV-Cnegative patients during 8 years of follow-up. P P Response to HAART In January 1997, all 80 patients began taking HAART. Among the 17 GBV-Cpositive patients, 10 received zidovudine, lamivudine, and saquinavir and 7 received zidovudine, lamivudine, and indinavir. Among the 63 GBV-Cnegative patients, 20 were treated with zidovudine, lamivudine, and saquinavir; 20 were treated with zidovudine, lamivudine, and indinavir; 13 were treated with zidovudine, didanosine, and indinavir; and 10 were treated with zidovudine, lamivudine, and ritonavir. Fourteen patients, 2 in the GBV-Cpositive group and 12 in the GBV-Cnegative group, stopped taking HAART between 1997 and 2001 because of personal preference, lack of adh

Effects of a short outpatient rehabilitation treatment on disability of multiple sclerosis patients - A randomised controlled trial

It is well known that neurorehabilitation can reduce disability or improve handicap of people with multiple sclerosis (MS). The aim of this study was to evaluate the effectiveness of a short period (6 weeks) of a tailored, individualised outpatient rehabilitation program in people with progressive MS. A randomised-controlled trial was undertaken in patients with primary and secondary progressive MS referred to the Centro Sclerosi Multipla of Catania. One hundred and eleven patients were assessed at baseline and at 12 weeks with validated measures of disability (Functional Independence Measure (FIM)) and impairment (Expanded Disability Status Scale (EDSS) and Functional Systems Scale). Of the 111, 58 were randomly assigned to the treatment group and 53 to the control group. All patients had been previously trained in a home exercise program. Both groups were well matched for age, sex, disease duration and severity, disability and quality of life (Short Form-36). At the end of 6 weeks patients allocated to the rehabilitation treatment group showed significant improvement in their level of disability compared with the control group,while the level of impairment did not change. Thirty-two patients of the treatment group and four of the control group improved on the FIM by two or more steps at 12 weeks (p<0.0001). An improvement by 1 EDSS step occurred in only two patients of the treatment group and in one patient of the control group. Benefits were maintained for a further six weeks. This study demonstrates that a short outpatient rehabilitation treatment improves disability of MS patients, without changing their impairment and confirms the effectiveness of rehabilitation in people with MS.Abstract.It is well known that neurorehabilitation can reduce disability or improve handicap of people with multiple sclerosis (MS). The aim of this study was to evaluate the effectiveness of a short period (6 weeks) of a tailored, individualised outpatient rehabilitation program in people with progressive MS. A randomised-controlled trial was undertaken in patients with primary and secondary progressive MS referred to the Centro Sclerosi Multipla of Catania. One hundred and eleven patients were assessed at baseline and at 12 weeks with validated measures of disability (Functional Independence Measure (FIM)) and impairment (Expanded Disability Status Scale (EDSS) and Functional Systems Scale). Of the 111, 58 were randomly assigned to the treatment group and 53 to the control group. All patients had been previously trained in a home exercise program. Both groups were well matched for age, sex, disease duration and severity, disability and quality of life (Short Form-36). At the end of 6 weeks patients allocated to the rehabilitation treatment group showed significant improvement in their level of disability compared with the control group,while the level of impairment did not change. Thirty-two patients of the treatment group and four of the control group improved on the FIM by two or more steps at 12 weeks (p<0.0001). An improvement by 1 EDSS step occurred in only two patients of the treatment group and in one patient of the control group. Benefits were maintained for a further six weeks. This study demonstrates that a short outpatient rehabilitation treatment improves disability of MS patients, without changing their impairment and confirms the effectiveness of rehabilitation in people with MS.

A Placebo-Controlled Treatment Trial of Blastocystis hominis Infection with Metronidazole

Blastocystis hominis, previously considered a harmless yeast, is now classified as a protozoan inhabiting the human intestinal tract. The pathogenicity of B. hominis remains controversial and is currently the subject of extensive debate.1- 5 As a result of the uncertainty surrounding the pathogenic role of B. hominis, large-scale treatment trials of B. hominis infection have so far been lacking. In spite of this, several drugs have been reported to be active against the parasite.6-8 The present study was carried out in order to evaluate the efficacy of metronidazole treatment in inducing clinical remission and parasitologic eradication in immunocompetent individuals with B. hominis as the only evident cause of diarrhea.

Effect of indomethacin on adenosine-induced bronchoconstriction

The exact mechanism of adenosine-induced bronchoconstriction in patients with asthma is unknown. Adenosine contraction of guinea pig trachea was antagonized by inhibitors of cyclooxygenase. The aim of this study was to investigate the effect of indomethacin (100 mg/day) on adenosine-induced bronchoconstriction in 14 asymptomatic patients with asthma. Airway response was evaluated as FEV1, and adenosine was administered as an aerosol diluted in 0.9% saline to produce a concentration range of 0.125 to 4 mg/ml. The dose of adenosine producing a 20% change in FEV1 (PD20) was calculated from the individual semilogarithmic dose-response curve; the results of PD20 were converted to log values for statistical analysis (Students paired t test). The study was performed on 3 separate days. On the first day, the adenosine challenge was performed, and on subsequent days patients were pretreated with either placebo or indomethacin in a randomized, double-blind manner. Inhaled adenosine caused bronchoconstriction with a geometric mean PD20 of 0.71 mg (95% confidence limits, 0.44 to 1.16). After placebo, a geometric mean PD20 of 0.91 mg (95% confidence limits, 0.53 to 1.58) was obtained. Indomethacin pretreatment decreased adenosine hyperresponsiveness and shifted the dose-response curves of adenosine challenge to the right with a geometric mean PD20 of 1.28 mg (95% confidence limits, 0.64 to 2.56). The effect of indomethacin on adenosine bronchoconstriction (p less than 0.01 versus baseline; p less than 0.05 versus placebo) suggests an indirect mechanism of adenosine on inducing release of arachidonic acid derivatives. Inflammatory mediators inhibited by indomethacin may be involved in adenosine bronchoconstriction, even if this mechanism is not relevant.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of Serum Melatonin Levels in HIV-1- Infected Individuals' Parallel Disease Progression: Correlation with Serum Interleukin-12 Levels

Abstract.Background:During the natural history of human immunodeficiency virus type I (HIV-1) infection, an impairment of interleukin-12 (IL-12) production precedes a switch from a T-helper 1 (Th1) to a T-helper 2 (Th2) stage of cellular immunity. Melatonin, the main hormone produced by the pineal gland, seems to promote a Th1 response by increasing the production of IL-12 in vitro. The aim of this study was to measure and correlate serum levels of melatonin and IL-12 in a cohort of HIV-1-infected individuals.Patients and Methods:77 anti-HIV-1-positive subjects were enrolled: 20 were in CDC stage A, 25 in CDC stage B and 32 in CDC stage C. 30 healthy HIV-1-seronegative subjects were recruited as controls. IL-12 and melatonin concentrations were quantitated in serum samples.Results:Mean levels of serum melatonin were significantly lower in HIV-1-infected individuals in comparison with controls (p < 0.001). Within the HIV-1-seropositive group, mean melatonin and IL-12 concentrations were significantly lower in patients in CDC stage C, as compared with patients in CDC stages B and A (p < 0.01).Conclusion:During the natural history of HIV-1 disease, serum melatonin levels are progressively reduced. This reduction may be related to the impairment of Th1 immunoresponses.

Health-related quality of life in patients with hepatocellular carcinoma after hepatic resection, transcatheter arterial chemoembolization, radiofrequency ablation or no treatment

BACKGROUND Aim of this work was to compare quality of life (QoL) of patients affected by HCC and submitted to hepatic resection (HR), transarterial chemoembolization (TACE), radiofrequency ablation (RFA), or no treatment (NT). METHODS Patients affected by HCC between 2001 and 2009 were considered for this study. Gender, diabetes, hepatitis status, Child grade, tumor size, and recurrence were analyzed. QoL was assessed before treatment and 3, 6, 12, and 24 months after, using a FACT-Hep questionnaire. P value was considered significant if <0.01 and highly significant if <0.001. RESULTS Fourteen patients (27.45%) were treated with HR, 15 patients (29.41%) underwent TACE, RFA was performed in 9 patients (17.65%), and 13 patients (25.49%) were not treated. Physical well-being, social/family well-being, emotional well-being, functional well-being and additional concerns 24 months after HR were significantly higher compared to all other treatments. CONCLUSIONS Hepatic resection provides the best QoL at 24 months. RFA provides a worse QoL compared to HR, but a higher QoL compared to TACE or NT.

Treatment of bisphosphonate-related osteonecrosis of the jaws: presentation of a protocol and an observational longitudinal study of an Italian series of cases

The aim of this study was to evaluate the efficacy of a treatment protocol for bisphosphonate-related osteonecrosis of the jaws (BRONJs). We conducted a longitudinal observational non-controlled study in 94 patients with confirmed BRONJ. Treatment was in two phases: supportive (antimicrobial mouth rinses, antibiotics, and anti-inflammatory steroids) to minimise infection and pain before the formation of a bony sequestrum; and surgical plus pharmacological treatment (sequestrectomy with antibiotic prophylaxis) after the sequestrum had developed. We did a Kaplan-Meier analysis (survival curve) to evaluate the time from the initial assessment until the formation of the bony sequestrum (endpoint), and a log-rank (Mantel-Haenszel) test to compare the formation times of the sequestra in men and women. Ninety-one of the 94 patients developed sequestra and were operated on. Three patients were withdrawn from the study because of severe pain and were treated by debridement before the sequestra developed. The results showed that sequestra developed within 15 months in all 91 patients. The Kaplan-Meier analysis showed that the mean time to formation of a sequestrum was 8 months (range 5-11). The difference between the mean time for men (5 months, range 2-8) and women (9 months, range 6-12) was highly significant (p<0.0001). Within the limits of this study, we conclude that by waiting for the formation of bony sequestra while controlling infection and pain, it is possible to do a conservative resection, unless pain is severe or there is a risk of fracture. This non-aggressive approach permits the removal of all necrotic bone, avoids damage to adjacent healthy bone, and does not result in recurrences.

Decreased amplitude of auditory event-related delta responses in Alzheimer's disease

The present study assessed auditory event-related potentials in patients with Alzheimers disease (AD). Delta responses of 21 mild probable AD subjects according to NINCDS-ADRDA criteria, and 16 healthy elderly controls were evaluated by an active oddball paradigm. Averaged and single sweep potentials were analyzed during target tone processing. As far as time domain averaged event-related potentials (ERPs) are concerned, no significant group differences were observed for N100 and P200 components (both latency and amplitude); also, N200 and P300 amplitude did not differ between groups, whilst N200 and P300 latency were significantly prolonged in AD patients. Concerning delta frequency component of the averaged ERPs, no significant differences between groups were obtained for delta response amplitude as well as delta response topography (Fz, Cz, Pz). Analysis of delta responses was performed for single sweep maximal peak-to-peak amplitude. Significant between groups differences were revealed at the level of single sweep amplitude at the 3 midline sites (Fz, Cz, Pz), during target tone processing. In particular, the difference between healthy controls and AD subjects was at the level of stimulus-related delta amplitude changes: in all locations a significant enhancement of the delta response is recorded in healthy subjects (especially at the frontal location), whilst this delta reactivity was not detectable in AD patients. From a clinical point of view, the lack of delta reactivity might relate to a decision-making function impairment since mild Alzheimers disease.

Enhancing effect of dipyridamole inhalation on adenosine‐induced bronchospasm in asthmatic patients

The study was performed on 13 asthmatic patients to determine whether inhaled dipyridamole would act directly by inducing bronchoconstriction or indirectly by potentiating the adenosine‐induced bronchoconstriction. The study was performed in 3 consecutive days. On the first day adenosine challenge was performed and the PD20 value calculated. On the other days the adenosine challenge was done 5 min after randomized inhalations of dipyridamole or a control solution. The mean percent change in FEV1 after dipyridamole (Δ%= 2.0) and control solution (Δ%= 1.0) was not significant. Inhaled adenosine caused bronchoconstriction with a geometric mean PD20 of 1.09 mg. After control solution inhalation, a mean PD20 value of 1.31 mg was observed. Dipyridamole inhalation increased adenosine hyperresponsiveness and in all subjects shifted the dose‐response curves of adenosine challenge to the left with a mean PD20 value of 0.40 mg. This enhancing effect of dipyridamole was significant when compared with the baseline value (P < 0.01) and control solution (P < 0.O1). The study demonstrated that dipyridamole inhalation increased airway responsiveness to adenosine in all subjects. This effect is due to indirect activity of dipyridamole on airways without changes in baseline airway caliber.