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Biomedical subjects

A Grossi

Publications and source records attributed to A Grossi.

At least 19 recordsLinked to original sources

Neutral wrist splinting in carpal tunnel syndrome: a 3- and 6-months clinical and neurophysiologic follow-up evaluation of night-only splint therapy.

AIM: The aim of the study was to evaluate the long-term efficacy of night-only splint wear therapy for carpal tunnel syndrome (CTS). METHODS: We conducted a randomized case-control trial with evaluation after three and six months of follow-up of outpatients with mild, recent onset symptoms of CTS recruited from the department clinic. Fifty patients (50 hands) were enrolled, of which 36 completed the study at 6 months. The case group utilized a thermoplastic neutral wrist splint for night-only wear. Outcome measures were instrumental parameters (sensory and motor nerve conduction velocity), symptom and function alterations (as measured by Levine's self-administered questionnaire), clinical parameters (pressure-provocative and Phalen tests). RESULTS: Improvements were observed in Levine's symptom status score at the three-month (P=0.001) and the six-month (P=0.001) follow-up visits, in functional score (P=0.0001) and (P=0.0004), in median distal sensory latency (P=0.01) and (P=0.02), in pressure-provocative test outcome (P=0.01) and (P=0.003), in Phalen test outcome (P=0.04) and (P=0.05) respectively. CONCLUSION: Symptom relief and neurophysiological improvement after night-only splint wear therapy lasted up to the six-month follow-up visit.

Carpal Tunnel Syndrome↗

VEGF inhibition and cytotoxic effect of aplidin in leukemia cell lines and cells from acute myeloid leukemia.

BACKGROUND: Aplidine (APL) is a marine depsipeptide isolated from the Mediterranean tunicate Aplidium albicans that is under clinical phase II development. In contrast to the lack of bone marrow toxicity reported in phase I/II studies, it has been shown to induce cytotoxicity at very low concentration against lymphoblastic leukemia blast, as well as having an impact in the vascular endothelial growth factor (VEGF)/VEGF receptor 1 loop. PATIENTS AND METHODS: To confirm these findings we investigated APL-related VEGF inhibition and its cytotoxic effect on myeloid leukemic cells lines (K-562, HEL and HL60) and fresh leukemia blasts derived from 30 patients with acute myeloid leukemia (AML). The conventional active 4-demetoxi-daunorubicin (idarubicin; IDA) was included as a positive control. RESULTS: APL was found to be significantly (P<0.001) more active than IDA in obtaining 50% growth-inhibition in K-562, HEL and HL60 cell lines. Results obtained with AML blast cells were super imposible. ID(50) ranged from 0.024 to 0.610 microM for IDA (0.200+/-0.176) and from 0.001 to 0.108 microM for APL (0.020+/-0.031). Annexin V tests and cell cycle analysis performed on cell lines confirmed the stronger citotoxic capability of APL as apoptotic inducer and as a G(1) blocker. The inhibitory effects of APL on VEGF release and secretion have been confirmed by ELISA tests performed on HEL: the VEGF concentration in cell surnatant was reduced from 169 to 36 pg/ml after 24 h of exposure to a pharmacological concentration of APL. CONCLUSIONS: APL harbors a strong in vitro antileukemic activity at a concentration achievable in patients at non-myelotoxic doses. Our data also support the notion of an impact on VEGF secretion. Clinical studies with this new marine-derived compound in relapsed/resistant leukemia are underway.

Acute Disease↗

Impact of a new dosing regimen of epoetin alfa on quality of life and anemia in patients with low-risk myelodysplastic syndrome.

This study evaluated the impact of a new epoetin alfa dosing regimen on quality of life (QOL), transfusion requirements, and hemoglobin (Hb) levels in 133 patients with low-risk myelodysplastic syndrome (MDS) and Hb < or =10 g/dl. Epoetin alfa 40,000 IU was given subcutaneously twice weekly; after 4 weeks, the dose could be reduced to 40,000 IU weekly in patients achieving erythroid response. QOL was assessed using the functional assessment of cancer therapy-anemia (FACT-An) questionnaire. FACT-An scores increased on average by 7.5 after 4 weeks and by 8.8 after 8 weeks compared with baseline. FACT-An scores were positively associated with Hb values (r=0.53, P<0.01). The mean FACT-An score increase at week 8 was 10.2 in responders and 5.6 in nonresponders. The overall erythroid response rate at week 8 was 68%: 74% in transfusion-independent patients and 59% in transfusion-dependent patients. Of all responders at week 8, response was maintained in 86% at week 12, 71% at week 16, 65% at week 20, and 54% at week 24. Treatment was generally well tolerated. Our data provide new and encouraging results regarding the benefits of 40,000 IU biweekly induction doses followed by 40,000 IU weekly in improving QOL, correcting anemia, and reducing transfusion requirements in low-risk MDS patients.

Adult↗

Management of cancer anemia.

Anemia complicates the course of disease in about 50% of patients with cancer, and negatively affects their quality of life. A correct approach to therapy should consider all the possible causes and patients need to be treated accordingly. The observation that erythropoietin production is often blunted offers new treatment possibilities. Fifty to 70% of anemic patients respond to rHuEpo, given in a three times or once-a-week schedule. The novel hyperglycosylated protein darbepoetin permits longer intervals between administrations, thanks to its longer half-life, and a once per cycle or once-a-month schedule is a reasonable target. Correction of anemia improves the quality of life, and it has been hypothesized that improvement of cognitive function may derive from a direct effect of Epo on CNS cells. Although anemia is an adverse prognostic factor in cancer, results of recent clinical trials have raised the question whether rHuEpo may favor neoplastic cell proliferation. Results are conflicting at the moment, and further studies are required before arriving at a conclusion. Data available so far do not indicate any negative effect of darbepoetin on the outcome of cancer disease, nor has the production of anti-darbepoetin antibodies or PRCA been reported, a complication observed in less than 200 patients with anemia due to renal insufficiency and treated with rHuEpo alpha.

Anemia, Iron-Deficiency↗

Prevalence and drug susceptibility of pathogens causing bloodstream infections in northern Italy: a two-year study in 16 hospitals.

The epidemiology of bacterial pathogens causing bloodstream infection was studied in 16 hospitals in Lombardy (northern Italy) over a 2-year period (1999 and 2000). Overall, 2924 microorganisms causing significant bacteremia were collected. The most frequent isolates were Escherichia coli ( n=663; 22.7%), Staphylococcus aureus ( n=534; 18.3%), Staphylococcus epidermidis ( n=242; 8.2%), and Pseudomonas aeruginosa ( n=176; 6.0%). Unlike Escherichia coli, which was usually acquired from the community, Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa were usually acquired in hospitals. Rates of resistance to oxacillin and its associated traits were significantly higher among hospital-acquired staphylococci as compared to those of isolates from the community. Escherichia coli was highly susceptible to extended-spectrum cephalosporins, with a very low percentage of strains producing extended-spectrum ss-lactamases (ESBLs). On the contrary, production of ESBL appeared to be an important mechanism of resistance among nosocomial isolates of Klebsiella pneumoniae. Resistance to ciprofloxacin was widespread in several members of the family Enterobacteriaceae, with rates often exceeding 10%. Moreover, with regard to ciprofloxacin, there were no significant differences between rates of resistance among Enterobacteriaceae causing hospital-acquired infections versus those causing community-acquired infections. Multidrug resistance was commonly observed in Pseudomonas aeruginosa, indicating the need for new antimicrobial agents that are more active against nonfermentative gram-negative bacteria. In conclusion, epidemiological studies of the prevalence and antimicrobial susceptibility patterns of blood isolates in northern Italy appear to provide useful information for both empirical treatment of suspected infections and better management of patients.

Adult↗

Long-term intrathecal Baclofen infusion in supraspinal spasticity of adulthood.

OBJECTIVE: To evaluate long-term results of chronic intrathecal Baclofen infusion on the spasticity, on the spasms and to evaluate the side-effects of the intrathecal Baclofen in patients with supraspinal spasticity. CLINICAL MATERIALS AND METHODS: Fourteen patients with severe progressive refractory to medical therapy spasticity were evaluated after chronic intrathecal Baclofen infusion performed by implantation of subcutaneous pump. The patients had suffered traumatic or anoxic acquired brain injuries. The clinical evaluation was made using Ashworth Scale (AS) and the Spasm Frequency Scale (SFS). RESULTS: The intrathecal therapy showed a statistically significant improvement of the tone and of the spasms. CONCLUSIONS: The intrathecal infusion of Baclofen seems to be an effective treatment in patients with supraspinal spasticity.

Adolescent↗

European Confederation of Medical Mycology (ECMM) prospective survey of candidaemia: report from one Italian region.

An ECMM epidemiological prospective survey of candidaemia was performed in one Italian region (Lombardy; population: 8 924 870) by the National Society of Medical Mycology (FIMUA) from September 1997 to December 1999. In total, 569 episodes were reported with an overall rate of 0.38/1000 admissions, 4.4/100000 patient days. Predisposing factors included presence of an intravascular catheter (89%), antibiotic treatment (88%), surgery (56%), intensive care (45%), solid tumour (28%), steroid treatment (15%), haematological malignancy (7%), HIV infection (6%), fetal immaturity (4%). Mucous membrane colonization preceded candidaemia in 83% of patients. Candida albicans was identified in 58% of cases, followed by Candida parapsilosis (15%), Candida glabrata (13%), Candida tropicalis (6%). Septic shock occurred in 95 patients. Crude mortality was 35%, the highest in C. tropicalis fungaemia (44%), the elderly (64%) and solid tumour cancer patients (43%). Intravascular catheter removal was associated with higher survival rate (71 vs. 47%). This survey underscores the importance of candidaemia in hospital settings.

Adolescent↗

Chordal plication and free edge remodeling for mitral anterior leaflet prolapse repair: 8-year follow-up.

BACKGROUND: Chordal suture plication and free edge remodeling represent a personal technique for the repair of anterior leaflet prolapse. We report the results of an 8-year experience. METHODS: Sixty-one patients with degenerative mitral regurgitation caused by prolapse of the anterior leaflet (11) or both leaflets (50) underwent anterior leaflet prolapse repair. Twenty patients who had associated cardiac procedures are included. RESULTS: There were two perioperative deaths. Postoperative mitral regurgitation fell to 0.4 +/- 0.7 versus 3.7 +/- 0.4 preoperative (p < 0.0001). Mean follow-up was 40.5 months. There were 3 late deaths and 3 mitral reoperations (1 of 3 repairs, 2 of 3 replacements). Thromboembolism and endocarditis occurred in 1 patient each. Actuarial overall survival, freedom from cardiac death, and freedom from mitral reoperation at 92 months were 85.1% +/- 7.9%, 88.9% +/- 7.7%, and 94.6% +/- 3.0%, respectively. CONCLUSIONS: Our technique of anterior leaflet prolapse repair appears effective, safe, and durable at mid- to long-term follow-up, and may be used in the presence of extensive disease of both leaflets.

Adult↗

Safety and efficacy of thalidomide in patients with myelofibrosis with myeloid metaplasia.

We administered the anti-angiogenic drug thalidomide to 21 patients (12 men) with myelofibrosis with myeloid metaplasia (MMM), who were not responsive to standard treatment. Patients received thalidomide at an escalating dose from 100 to 400 mg/d. Administration of the drug was discontinued before the planned 6 months of treatment in 19 patients (90.5%), mainly because of somnolence and/or fatigue, neurological symptoms or neutropenia. Of the 13 evaluable patients (who received more than 30 d of therapy), anaemia improved in three out of seven (43%) who were treated because of anaemia; thrombocytopenia improved in two out of three (66.6%) who were treated because of thrombocytopenia; splenomegaly was reduced in four (30.8%). Undesired increases in white blood cell and platelet counts were observed in three (23.1%) and five (38.5%) patients respectively. A severity score, indexed on haematological and clinical parameters, improved in two patients (15.4%), but worsened in five (38.5%). In conclusion, standard-dose thalidomide in MMM patients is burdened with a high rate of side-effects, which prevent prolonged treatment. Because the drug is effective in improving anaemia and thrombocytopenia and in reducing splenomegaly, low-dose therapy warrants evaluation. The unexpected observation of leucocytosis and thrombocytosis suggests biological studies and better criteria for selection of patients for treatment.

Adult↗

Patency of anastomoses after bilio-intestinal bypass: radioisotope demonstration.

BACKGROUND: Bilio-intestinal bypass (BIB) is effective for the treatment of refractory obesity. BIB permits bile flow into the non-functional jejunum, whereas food transit occurs via the remaining intestine. We used the radioisotope method of 99mTc-Hida cholescintigraphy (HC) in the follow-up of patients. METHODS: 21 patients were studied 3 months to 3 years after BIB with HC. After 3 hours acquisition, images were reviewed by two independent observers. Regions of interest (ROIs) were drawn on images: liver parenchyma, cholecysto-jejunal anastomosis (CC), choledochus (COL). Radioactivity taken up by liver was compared with radioactivity of CC and COL. % radioactivity passing through CC (%CC) and through COL (%COL) were determined. The final parameter, -COL, indicates the radioactive bile which does not pass through the choledochus. RESULTS: Anastomoses were found patent a few months to 3 years after operation. -COL showed linear correlation with the decrease in cholesterolemia and in body weight in the 1st year after BIB. CONCLUSIONS: HC shows passage of radioactive bile through anastomoses and provides semiquantitative evaluation of bile flux diversion. Bile flux towards the gallbladder and non-functional jejunal limb far exceeds flux directed towards the duodenum via the choledochus.

Adult↗

Searching for the magic bullet against cancer: the butyrate saga.

n-Butyric acid and its "polymorphic" derivatives have been largely but somehow "blindly" studied in oncology and in red cell diseases with consistent results through decades indicating a strong maturative effect determined by enhancement of gene transcription. Although these effects have been observed mainly in vitro, the relative absence of systemic toxicity of butyrates render these compounds appealing as specific therapeutic agents. More interestingly, their specific mechanism of action, i.e. inhibition of histone deacetylase and de-repression of transcription represents at present an unique tool for diseases such as acute leukemias which are characterised by a disregulation of co-repressors and co-activators of gene transcription. More insight into specificity and modalities of action of different butyrate derivatives may be a guarantee for excellent tailored antileukemic therapy in the future.

Antineoplastic Agents↗

Hashimoto's disease during interferon-alpha therapy in a patient with pre-treatment negative anti-thyroid autoantibodies and with the specific genetic susceptibility to the thyroid disease.

OBJECTIVES: The authors described a case of Hashimoto's disease during interferon-alpha (IFN-alpha) treatment for chronic viral C hepatitis in a patient with the specific genetic susceptibility associated with the thyroid disease. RESULTS: A 60-year-old woman with chronic active viral C hepatitis (HCV genotype = 3a) started IFN-alpha therapy in November '96. Before treatment thyroid function tests were normal and anti-thyroid (anti-thyroglobulin and anti-thyroid peroxidase) Abs were negative. During IFN therapy, serum aminotransferases fell within the normal range and viremia (serum HCV-RNA) became negative after one year. After 20 months, the patient presented clinical features of primary hypothyroidism. Anti-thyroid Abs were found positive. Hormonal, ultrasonographic, radioiodine scanning and fine needle aspiration findings were consistent with the diagnosis of Hashimoto's thyroiditis. The tissutal typing of the patient showed the presence of Human Leukocyte Antigen (HLA) DRB1*11 gene (corresponding to DR5 antigen). IFN-alpha therapy was suspended and a treatment with l-T4 started. Chronic viral infection relapsed after the suspension of the IFN-alpha therapy. CONCLUSIONS: This case report showed that the clinical appearance of Hashimoto's disease after IFN-alpha therapy for chronic C hepatitis in our patient was associated with a specific genetic predisposition (DR5) for this pathology. Further studies are necessary to evaluate whether the study of HLA antigens may be a very useful tool to detect the patients with a predisposition to develop autoimmune thyroiditis, in order to make a early diagnosis of thyroid disorders during the IFN-alpha treatment.

Autoantibodies↗

Amifostine in the treatment of low-risk myelodysplastic syndromes.

BACKGROUND AND OBJECTIVE: The phosphorylated aminothiol agent amifostine (Ethyol) protects bone marrow and other tissues from toxicity due to ionizing radiation and antineoplastic drugs, and stimulates progenitors from normal and myelodysplastic bone marrow. Contrasting results have been published so far on the effectiveness of amifostine in correcting cytopenia in patients with myelodysplastic syndromes (MDS). DESIGN AND METHODS: In a pilot phase II study we treated 26 patients with low risk MDS (13 RA, 2 RARS, 2 CMML, 9 RAEB with blasts < 10%) with amifostine (200 mg/m(2 )x 3/week for 4 weeks). RESULTS: Hemoglobin concentration, reticulocyte, neutrophil and platelet counts increased respectively in 6 (23%), 11 (42%), 13 (50%) and 9 (34%) of patients. Red cell transfusions were reduced (> 50%) in 4/26 patients and abolished in 1/26. Unexpectedly a significant decrease in soluble transferrin receptor level at week 4 of therapy, compared to the basal level (p<0.04), was observed in the whole population of patients. INTERPRETATION AND CONCLUSIONS: Amifostine can ameliorate cytopenia in some patients with MDS, with few and mild side effects. Neutropenia is more likely to be corrected than anemia or thrombocytopenia. Mechanisms underlying this biological effect remain to be clarified.

Aged↗

Hereditary thrombocytopenia due to reduced platelet production--report on two families and mutational screening of the thrombopoietin receptor gene (c-mpl).

Hereditary thrombocytopenias represent heterogeneous clinical and genetic syndromes. They include a consistent group of families which are considered as a separate clinical entity, characterized by autosomal dominant transmission, incomplete penetrance in females, chronic thrombocytopenia with early age of onset and frequently increased platelet volume, without any other hematologic abnormality. The molecular defect in these families is still unknown. We describe 2 families in 3 generations (10 patients), and report the first study of the TPO/c-mpl system in autosomal dominant thrombocytopenia. We performed mutational screening of c-mpl coding, flanking introns and promoter regions in 2 probands from the two families by DNA sequencing. The results do not provide evidence of c-mpl sequence alterations in either of the 2 families investigated. Moreover, the normal TPO serum levels detected in 5 patients from each family leads us to exclude the possibility of a defect in TPO production in our families. Finally, the involvement of both c-mpl and TPO genes in the pathogenesis of thrombocytopenia in these two families was excluded by negative results of linkage analysis.

Adolescent↗

[Repair of anterior mitral leaflet prolapse: state of the art].

Surgical repair of anterior leaflet prolapse has evolved and widely expanded over the past decade. A number of surgical techniques have been developed. In this study a review of all reparative techniques has been provided. A classification has been proposed according to the involvement of valve components and, eventually, to graft employment. For each technique the following points have been detailed: a) advantages and drawbacks; b) likelihood of effective valve repair based on morpho-pathologic variability of degenerative mitral disease; c) long-term outcome as freedom from reoperation. The authors provide indications for early surgical anterior leaflet prolapse repair and recommend that surgeons should be familiar with many reparative procedures to select the right option and improve their operative results.

Cardiac Surgical Procedures↗