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Biomedical subjects

Antonio Greco

Publications and source records attributed to Antonio Greco.

8 recordsLinked to original sources
PubMed2006

Carbohydrate recognition by Clostridium difficile toxin A.

Clostridium difficile TcdA is a large toxin that binds carbohydrates on intestinal epithelial cells. A 2-A resolution cocrystal structure reveals two molecules of alpha-Gal-(1,3)-beta-Gal-(1,4)-beta-GlcNAcO(CH(2))(8)CO(2)CH(3) binding in an extended conformation to TcdA. Residues forming key contacts with the trisaccharides are conserved in all seven putative binding sites in TcdA, suggesting a mode of multivalent binding that may be exploited for the rational design of novel therapeutics.

Bacterial Toxins↗
PubMed2005

Crystal structure of receptor-binding C-terminal repeats from Clostridium difficile toxin A.

Clostridium difficile is a major nosocomial pathogen that produces two large protein toxins [toxin A (TcdA) and toxin B (TcdB)] capable of disrupting intestinal epithelial cells. Both belong to the family of large clostridial cytotoxins, which are characterized by the presence of a repetitive C-terminal repetitive domain (CRD). In TcdA, the CRD is composed of 39 repeats that are responsible for binding to cell surface carbohydrates. To understand the molecular structural basis of cell binding by the toxins from C. difficile, we have determined a 1.85-A resolution crystal structure of a 127-aa fragment from the C terminus of the toxin A CRD. This structure reveals a beta-solenoid fold containing five repeats, with each repeat consisting of a beta-hairpin followed by a loop of 7-10 residues in short repeats (SRs) or 18 residues in long repeats (LRs). Adjacent pairs of beta-hairpins are related to each other by either 90 degree or 120 degree screw-axis rotational relationships, depending on the nature of the amino acids at key positions in adjacent beta-hairpins. Models of the complete CRDs of toxins A and B suggest that each CRD contains straight stretches of beta-solenoid composed of three to five SRs that are punctuated by kinks introduced by the presence of a single LR. These structural features provide a framework for understanding how large clostridial cytotoxins bind to cell surfaces and suggest approaches for developing novel treatments for C. difficile-associated diseases by blocking the binding of toxins to cell surfaces.

Amino Acid Sequence↗
PubMed2005

Deep venous thrombosis in elderly hospitalized patients: prevalence and clinical features.

BACKGROUND AND AIMS: It is not known whether old age influences the clinical outcome of deep venous thrombosis (DVT) in patients admitted to acute internal medicine wards. This study aimed at evaluating the effect of age on the prevalence and clinical features of DVT in patients admitted to acute medical wards in a general hospital. METHODS: All patients with a discharge diagnosis of DVT during a 4-year period from 1999 to 2002 were identified. Age, gender, main and secondary diagnoses, diagnostic procedures, and length of stay (LOS) were recorded. The severity index was calculated by the All Patients Refined-Diagnostic Related Groups (APR-DRG) grouper and graded as mild, moderate, severe or extreme. RESULTS: 310 patients with DVT were identified: 163 males and 147 females. Mean age was 62 +/- 16 years, with a range of 17-94 years. 174 patients (56%) were over 65 years old (mean age = 74.2 +/- 6.2, range 65-94 years) and 136 (44%) were young or adults (mean age = 48.3 +/- 12.9, range 17-64 years). The overall prevalence of DVT was 1.51%, with no differences between males and females (1.46 vs 1.56%, p = NS). In elderly subjects, the prevalence of DVT was significantly higher than in young or adult patients (1.7 vs 1.2%, p = 0.005) and was more frequently associated with pulmonary embolism (12 vs 7%, p < 0.05) and less with neoplasms (10 vs 30%, p < 0.05) than in young patients. Diagnostic procedures performed during the hospital stay were similar for elderly and young patients whereas LOS was significantly longer in elderly than young patients (14.1 +/-11.5 vs 11.7 +/- 9 days, p < 0.05). The APR-DRG severity index was significantly higher in elderly than in young patients (p < 0.05). CONCLUSIONS: Elderly patients with DVT reveal higher prevalence and have different clinical features than young or adult patients. Further studies are needed to better evaluate predisposing conditions and clinical outcomes of DVT in old age.

Adolescent↗
PubMed2004

Incidence of post-thrombotic syndrome in patients with previous pulmonary embolism. A retrospective cohort study.

There is little information available about the true incidence of post-thrombotic syndrome (PTS) after pulmonary embolism (PE). The aim of this study was to investigate the incidence of PTS in patients with previous pulmonary embolism without concomitant ultrasonographically-detectable deep vein thrombosis (DVT). A retrospective cohort study was conducted at a single tertiary care centre, Cosenza, Italy. Forty-seven consecutive patients with proved PE without DVT within the previous 2 to 6 years, 45 patients with previous DVT in the same years, and 45 patients with diseases unrelated to venous thromboembolism (VTE) underwent a blind assessment for PTS using a clinical score. Two of 47 (4.2%, 95%CI: 0.01-9.9) patients with PE, 2 of 45 (4.4%, 95%CI: 0.01-10.4) patients with diseases unrelated to VTE, and 23 of 45 (53.3%, 95%CI: 38.7-67.9) patients with DVT showed signs and symptoms of PTS. The difference between the first two groups was not statistically significant (p = 0.7). In conclusion, the incidence of PTS after pulmonary embolism without DVT is low, and no different from that of patients without previous VTE.

Adult↗
PubMed2003

Diagnostic utility of echocardiography in patients with suspected pulmonary embolism.

The aim of this study was to investigate the clinical utility of echocardiography in the diagnosis of pulmonary embolism (PE). For this, we enrolled 162 patients with suspected PE in a prospective study. We evaluated the sensitivity and specificity of right ventricular dilatation, the Doppler evidence of pulmonary hypertension, and their possible associations. We also calculated the number of lung-scan angiography procedures avoided and the number of patients unnecessarily treated when echocardiography was included in the diagnostic work-up. The sensitivity and specificity of echocardiography ranged between 29 and 52% and between 96% and 87%, respectively. Adding echocardiography to the diagnostic strategy for PE would avoid about 12 to 28% of lung-scan angiography procedures, but would cause inappropriate treatment of 4 to 14% of all treated patients. The clinical utility of echocardiography in the diagnosis of PE is limited. The reduction in the number of standard diagnostic procedures obtained through its use would be counterbalanced by an excess of patients inappropriately treated.

Adolescent↗
PubMed2003

[Non-invasive hemodynamic assessment with bioimpedance in patients with subclinical hypothyroidism before and after treatment with levo-thyroxin].

Subclinical hypothyroidism is characterized by normal serum levels of free thyroxine and triiodothyronine with increased serum levels of thyroid-stimulating hormone (TSH) without symptoms. We evaluated by thoracic electrical bioimpedance cardiography the hemodynamic pattern of 38 patients with subclinical hypothyroidism, before and after 6-month therapy with levo(L)-thyroxine. We have not evidenced statistically significant differences for cardiac index, cardiac frequency and vascular peripheral resistances. TSH levels were decreased in a statistically significant way. Results obtained in our study show that hemodynamic pattern is not changed after hormone therapy in patients affected by subclinical hypothyroidism.

Adult↗
PubMedDate not supplied

Undercoding of Alzheimer's disease and related dementias in hospitalized elderly patients in Italy.

The prevalence of Alzheimer's disease (AD) and AD-related dementias (ADRD) in acute ward-hospitalized elderly patients is not well known, owing principally to misclassification and undercoding of AD and ADRD on hospital discharge abstract forms (DAFs). The aims of this study were to evaluate the prevalence of AD and ADRD, as evaluated by the DAF in elderly patients hospitalized in acute wards, and to compare clinical severity, length of stay, comorbidity, and number of diagnostic procedures in patients with AD versus ADRD to explain the different reimbursement costs of DRG12 (AD) versus DRG429 (ADRD). From the inpatient DAF database of the Casa Sollievo della Sofferenza Hospital, the DAFs of patients aged 65 years or over discharged from January 1, 2001, to March 31, 2003, with principal or secondary diagnoses of AD (ICD9-CM code 331) or ADRD (ICD9-CM codes from 290.0 to 290.43) were extracted and grouped by APR-grouper version 12. Age, gender, length of stay, principal and secondary diagnoses and procedures, and APR-DRG severity index (SI) and mortality risk (MR) were evaluated in these patients. Senile dementia was reported in 294 patients (0.58 percent, N = 50,253). In 123 patients (41.8 percent) dementia was the principal diagnosis, whereas in 171 patients (58.2 percent) dementia was reported on the DAF as a secondary diagnosis. Of the 123 patients with a principal diagnosis of dementia, 35 patients were included in the DRG-12 (AD) and 88 patients were included in the DRG-429 (ADRD). No differences were found in mean age, length of stay, comorbidity, or number of diagnostic procedures, as well as in the APR-DRG SI and APR-DRG MR between AD and ADRD patients. Conversely, reimbursement amounts were established as Euro4,033 for DRG-12 (AD) and Euro2,952 for DRG-429 (ADRD). AD and ADRD are undercoded in elderly hospitalized patients. The limits of the ICD9-CM classification system and the influence of reimbursement amounts may influence the coding reports by physicians.

Aged↗