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Biomedical subjects

L Calabrese

Publications and source records attributed to L Calabrese.

At least 19 recordsLinked to original sources
PubMed2006

Excess of nonceruloplasmin serum copper in AD correlates with MMSE, CSF [beta]-amyloid, and h-tau.

OBJECTIVE: To assess whether serum copper in Alzheimer disease (AD) correlates with cognitive scores, beta-amyloid, and other CSF markers of neurodegeneration. METHODS: The authors studied copper, ceruloplasmin, total peroxide, and antioxidants levels (TRAP) in serum; beta-amyloid in plasma; and copper, beta-amyloid, h-tau, and P-tau in the CSF of 28 patients with AD and 25 healthy controls, in relation to clinical status. RESULTS: Serum copper (p < 0.0001), peroxides (p = 0.002), a copper fraction unexplained by ceruloplasmin (p < 0.0001), and CSF h-tau (p = 0.001) were increased in AD, whereas serum TRAP (p = 0.03) and CSF beta-amyloid were decreased (p < 0.0001). Plasma beta-amyloid increased with age in healthy controls (r = 0.6; p = 0.05). CSF markers of AD correlated with serum copper variables. CSF copper was partially dependent on the serum copper fraction unexplained by ceruloplasmin (t = 2.2, p = 0.04). CSF beta-amyloid seemed to be related to serum copper (r = -0.46; p = 0.002). Mini-Mental Status Examination scores correlated positively with beta-amyloid (r = 0.46, p = 0.002) and inversely with copper unexplained by ceruloplasmin (r = -0.45, p = 0.003). CONCLUSIONS: The authors' results confirm the existence of changes in copper component distribution, particularly the copper fraction unexplained by ceruloplasmin and support the hypothesis of a beta-amyloid and copper connection in Alzheimer disease.

Aged↗
PubMed2006

Lymphatic mapping to tailor selective lymphadenectomy in cN0 tongue carcinoma: beyond the sentinel node concept.

PURPOSE: Cervical lymph node status is the most important pathological determinant of prognosis and decision making in head and neck squamous cell carcinoma (SCC). The aim of this study was to demonstrate that lymphoscintigraphy (LS) can supply a complete map of the lymphatic drainage before surgery, allowing planning of the type of intervention and serving to guide lymphadenectomy. METHODS: The study population comprised 14 patients with T2-4 SCCs of the tongue and clinically negative lymph nodes in the neck (cN0) who were scheduled to undergo tumour resection and selective level I-IV neck dissection extended to level V. LS was performed in all patients following the injection of (99m)Tc-colloidal sulphide in three aliquots around the primary lesion. Dynamic, static and tomographic images of the head and neck were acquired. The operative specimens were subjected to lymphoscintigraphic evaluation. Preoperative and postoperative imaging results were compared with the pathological findings. All nodes were examined using haematoxylin-eosin staining. RESULTS: Preoperative LS was successful in all patients. Preferential pathways of lymphatic drainage were identified: level II of the neck was the most common lymphatic drainage pattern, followed by levels IV and III. Contralateral drainage occurred in 11 patients and in two of them metastatic nodes were found on the contralateral side. Metastases were observed only in radioactive lymph nodes. CONCLUSION: LS is able to supply a complete map of the lymphatic drainage before surgery, making it possible to tailor selective neck dissection to each individual patient based on the results of preoperative mapping, thereby sparing healthy lymphatic tissue and reducing surgery-related morbidity.

Adult↗
PubMed2006

Review of 346 patients with free-flap reconstruction following head and neck surgery for neoplasm.

We present our 14-year experience of free tissue transfer following surgery for head and neck neoplasm. We evaluated 346 patients mean age 57 years, 65% had squamous cell carcinoma; the most frequent sites were oral cavity and mandible (168) craniomaxillo facial region (94) pharynx +/- cervical oesophagus and oropharyngostomes (84). In 327 (95%) cases the reconstruction was a success. Flap revision was necessary in 29 (8.4% of total) and recovery was successful in 10/29. Nine patients (2.6%) died perioperatively. Poor preoperative condition, previous treatment, and requirement for vein graft were significantly associated with increased risk of major complications after surgery. Cosmetic and functional outcomes were assessed on 1-10 scales: 69 and 77% of patients, respectively, had cosmetic and functional results in the 7-10 range, indicating successful outcome. Overall survival probabilities, estimated on 338 patients with malignant disease, were 53% at 2 years and 32% at 5 years. Most patients, but not all, had advanced disease stage, and 188 (54%) had recurrent disease. Hence, overall survival rates are acceptable and justify the use of complex reconstruction procedures in such patients.

Adolescent↗
PubMed2006

Mechanical behavior of quartz fiber reinforced epoxy resins for teeth restoration.

In this work composite materials, based on quartz fibers and epoxy resins, were employed with the aim to restore damaged teeth. The composite materials were chosen because they show biomechanical features very similar to that of the dentine, the main constituent of the tooth. Extracted teeth were rebuilt with two different restorative procedures: in the first, the composite material was pre-formed in a conical trunk shape abutment (PA) and then bonded to a fiber quartz post with a dental bonder. In the second rebuilt system the abutment was prepared by cross linking the resin on the fiber quartz post with a halogen lamp (CRA). The restored teeth were then mechanically tested and observed with a Scanning Electron Microscope (SEM) with the aim to study the interaction between the reconstructive materials. Wetting and roughness measurements were also carried out in order to study the interface adhesion between the post and the abutments. Characterization analysis evidenced that the CRA restorative procedure improves the adhesion between the substitutive materials and shows higher fracture strength than the PA ones. Anyway both the rebuilt systems are able to support the masticator load. An explanation of the interfacial post-abutment interaction phenomenon is discussed.

Adhesiveness↗
PubMed2005

Surgical planning in reconstruction of mandibular defect with fibula free flap: 15 patients.

The authors present a descriptive work on the reconstruction of large oromandibular defects with revascularized fibula free flaps in a group of patients treated by surgical resection of bony and soft tissues of the mandible. The principal objective is preoperative planning for the best morphological, functional, and aesthetic result. The authors report 15 reconstructions of wide oromandibular defects by revascularized fibula free flaps. The average patient age was 42 years. The mean follow-up period was 18 months. Correct surgical planning reduces surgical timing, minimizes the chance of failure during the reconstruction, and contemporaneously increases treatment efficacy and the best functional and aesthetic results.

Adult↗
PubMed2005

Diagnosis and management of neck metastases from an unknown primary.

Neck lymph node metastases from occult primary constitute about 5%-10% of all patients with carcinoma of unknown primary site. Metastases in the upper and middle neck (levels I-II-III-V) are generally attributed to head and neck cancers, whereas the lower neck (level IV) involvement is often associated with primaries below the clavicles. Diagnostic procedures include a careful clinical evaluation and a fiberoptic endoscopic examination of the head and neck mucosa, biopsies from all suspicious sites or blindly from the sites of possible origin of the primary, computerized tomography scan, and magnetic resonance. The most frequent histological finding is Squamous Cell Carcinoma, particularly when the upper neck is involved. In these cases, a systematic tonsillectomy in the absence of suspicious lesions is discussed since up to 25% of primary tumours can be detected in this site. Thoracic, and abdominal primaries (especially from lung, oesophagus, stomach, ovary or pancreas) should be sought in the case of adenocarcinoma and involvement of the lower neck. Positron emission tomography with fluoro-2-deoxy-D-glucose allows detection of primary tumour in about 25% of cases, but this procedure is still considered investigational. Therapeutic approaches include surgery (neck dissection), with or without post-operative radiotherapy, radiotherapy alone and radiotherapy followed by surgery as reported by several guide-lines. In early stages (N1), neck dissection and radiotherapy seem to have similar efficacy, whereas more advanced cases (N2, N3) require combined approaches. The extent of radiotherapy (irradiation of bilateral neck and mucosa versus ipsilateral neck radiotherapy) remains debatable. A potential benefit from extensive radiotherapy should be weighed against its acute and late morbidity and difficulties in re-irradiation in the case of subsequent primary emergence. The role of other methods, such as chemotherapy and hyperthermia, remains to be determined.

Aged↗
PubMed2004

Thyroid disease in northern Italian children born around the time of the Chernobyl nuclear accident.

BACKGROUND: The Chernobyl nuclear accident of 1986 caused a dramatic increase in the incidence of thyroid cancers in exposed children in Belarus. Airborne radioactivity from the reactor spread over northern Italy, where rainout gave rise to low levels of radioactivity at ground level. PATIENTS AND METHODS: As the latency between exposure to ionising radiation and development of thyroid cancer is thought to be about 10 years, in 1996/1997 all children born in 1985 and 1986 and attending school in an area of Milan, Italy were examined for thyroid nodules. A total of 3949 children were examined by two physicians blinded to the examination and diagnosis of the other. The children were to be reassessed in 2001/2002. RESULTS: In total, 1% had palpable nodules. The nodule diagnoses were: Hurtle cell adenoma (one), thyroglossal duct cyst (one), thyroid cyst (four) and thyroiditis (four). The prevalence of thyroid disease in the cohort was indistinguishable from that of populations not exposed to radioactive pollution. Only 10 children re-presented for examination 5 years later; all were negative. The direct costs of the study were estimated at 21,200 Euros. CONCLUSION: The high cost of the study in relation to reassuring lack of increase in thyroid nodule prevalence suggests that further studies are not justified.

Chernobyl Nuclear Accident↗
PubMed2004

The role of interleukin-1 in the pathogenesis of rheumatoid arthritis.

A significant body of experimental evidence has implicated the proinflammatory cytokine IL-1 in the pathogenesis of RA. For example, IL-1beta overexpression in rabbit knee joints causes arthritis with clinical and histological features characteristic of RA, whereas IL-1 deficiency is associated with reduced joint damage. In experimental models, IL-1 blockers, including IL-1 receptor antagonist (IL-1Ra), significantly reduce clinical and histological disease parameters. In RA patients, plasma and synovial fluid concentrations of IL-1 are elevated, and these correlate with various parameters of disease activity. The production of endogenous IL-1Ra, however, appears to be insufficient to balance these higher IL-1 levels. The efficacy of blocking IL-1 in patients with active RA has been established in controlled clinical trials of anakinra, a recombinant human IL-1Ra (r-metHuIL-1ra). When used alone or in combination with methotrexate, anakinra significantly reduces the clinical signs and symptoms of RA compared with placebo. Taken together, these results indicate that IL-1 plays an important role in the pathogenesis of RA.

Animals↗
PubMed2004

ChlVPP/ABVVP, a first line 'hybrid' combination chemotherapy for advanced Hodgkin's lymphoma: a retrospective analysis.

We retrospectively analysed toxicities and clinical results of 61 Hodgkin's lymphoma patients treated with chlorambucil, vinblastine, procarbazine, doxorubicin, bleomycin, vincristine and etoposide (ChlVPP/ABVVP), delivered in a weekly alternate schedule. Of 61 patients, 33 were in stages III-IV, 21 in stage IIB and seven in stage IIA with bulky disease or extranodal presentation. ChlVPP/ABVVP was administered for 6-8 cycles. Involved field radiotherapy (IFRT) (30-35 Gy) was delivered to 31 patients with residual disease after chemotherapy or bulky disease at diagnosis. Of 61 patients, 58 (95%) achieved complete clinical or radiological remission after chemotherapy and IFRT. With a median follow-up of 60 months, 5-year overall survival, relapse- and event-free survival were 78.8% (95% CI 68.2-91.1%), 81% (95% CI 70.6-92.2%) and 71.9% (95% CI 68.2-82.2%) respectively. Grades 3-4 neutropenia was the most relevant haematological toxicity and occurred in 82% of patients. Non-haematological toxicities were mild and reversible. No toxic deaths were recorded. One patient developed secondary acute myeloid leukaemia 1 year after ChlVPP/ABVVP. Due to the retrospective nature of this study, no definitive conclusions could be drawn about the clinical activity of ChlVPP/ABVVP. Nonetheless, clinical results seem better than those reported with standard regimens [ABVD (doxorubicin, bleomycin, vincristine, dacarbazine), MOPP (methotrexate, vincristine, procarbazine, prednisone), MOPP/ABVD] and as good as those reported using standard or escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone), with a lower degree of haematological and non-haematological toxicity. Long-term results of the ongoing randomized trial, comparing ABVD versus high-dose intensity weekly regimens will be useful to confirm our results.

Adolescent↗
PubMed2002

Structure to function relationships in ceruloplasmin: a 'moonlighting' protein.

Specialised copper sites have been recruited during evolution to provide long-range electron transfer reactivity and oxygen binding and activation in proteins destined to cope with oxygen reactivity in different organisms. Ceruloplasmin is an ancient multicopper dase evolved to insure a safe handling of oxygen in some metabolic pathways of vertebrates. The presently available knowledge of its structure provides a glimpse of its plasticity, revealing a multitude of binding sites that point to an elaborate mechanism of multifunctional activity. Ceruloplasmin represents an example of a 'moonlighting' protein that overcomes the one gene-one structure-one function concept to follow the changes of the organism in its physiological and pathological conditions.

Animals↗
PubMed2002

[Immediate post-extraction implant in infected site. An eight-year clinical and radiographic control].

The use of immediate post-extraction implants presents several advantages in term of reduction of surgical steps and time required to conclude the therapy. Particularly important is the possibility to minimize the bone loss that otherwise would occur in the physiologic healing of the alveolus. Many authors agree that an infected site is one of the main contraindications to use post-extraction implants. In spite of this, favourable results have been reported also in these conditions. In this study, an immediate post-extraction implant has been placed to substitute the maxillary left second premolar, extracted due to vertical root fracture. Suppuration with fistula in the vestibule was present. The residual wide bone defect at the end of the debridement of the surgical socket has made it necessary a regenerative procedure by means of e-PTFE membrane, at the same time of implant insertion. After 9 month-healing the membrane has been removed and the implant exposed to perform the prosthetic procedures. The clinical and radiographic control after 8 years prove that infection in the surgical site has not compromised the final success, even in the long-term observation, suggesting the need to re-evaluate the contraindications conventionally reported.

Adult↗
PubMed2001

Mandible reconstruction and autogenous frozen bone graft: experimental study on rats.

The aim of this study was to evaluate the biological behaviour of a frozen bone graft in orthotopic and heterotopic sites in the rat. The previous experimental study on this subject was published 25 years ago without sufficient detail about the histology and comparison between the orthotopic and ectopic sites. Therefore, being very important for future clinical application, we decided to evaluate the frozen bone graft using rats. The procedure was performed on two groups of five rats each (Charles River). After wide dissection of the inferior border of the mandible from the surrounding muscle, an inferior segmental resection 4 mm in length was performed, taking care not to fracture the superior part and to maintain mucosal integrity. This segment was placed in liquid nitrogen for two periods of 10 minutes each with a third period to allow it to reach room temperature. In the first group (A), the frozen segment was placed ectopically in a gluteal muscle pocket, and in the second group (B), the frozen bone was fixed in the same position in the same mandible. After 1 month of follow-up, the animals were killed, the bone graft was removed, and histology was performed. Results were consistent in both groups. In group A, the segment was surrounded by strong inflammatory reaction, with no vital cells or bone cells, but some vascular penetration. We concluded that there was no bone deposition and no bone rehabitation. In group B, the initial segment was strongly fixed to the remaining mandible, there was an increase of the macroscopic dimension that paralleled the increase in the dimension of the remaining mandible and the growth of the animal. The cortical part had thinned down, the medullary part presented signs of bone deposition as well as bone resorption and vascular penetration. The periosteum from the adjacent normal mandible was growing and covering the frozen bone graft, offering additional stimulus to the bone deposition. In conclusion, the frozen bone graft acts as a normal bone graft. It needs to be placed in contact with vascularised bone and surrounded by well vascularised soft tissue to allow deposition of new bone. If the frozen graft is placed ectopically, it will be surrounded by chronic inflammatory reaction with no bone deposition.

Animals↗
PubMed2001

Learning curve for translaryngeal tracheotomy in head and neck surgery.

OBJECTIVES: Translaryngeal tracheotomy (TLT) is a widely accepted procedure in intensive-care units for its simplicity of execution, low morbidity, rapid wound closure after cannula removal, good esthetic results, and lack of long-term sequelae. The aim of this study was to evaluate the feasibility and use of adopting TLT in patients with cancer undergoing major head and neck surgery. STUDY DESIGN: Prospective analysis of learning curve and incidence of complications in 41 patients with cancer who underwent TLT at the Division of Head and Neck Surgery of the European Institute of Oncology from November 1997 to June 1999. METHODS: Patient characteristics, pathology, anatomic characteristics of the neck, and surgical short-term and long-term complications were noted. The patients were divided into consecutive groups of six or seven patients, and time trends in occurrence of complications and time to execute the procedure were assessed. RESULTS: TLT performance time decreased from 50 minutes in the first seven patients to 24 minutes in the last group. The technique was easy to perform and safe, with only two minor complications during surgery. However, minor complications occurred in three and major complications in 17 patients in the days immediately following surgery, almost entirely attributable to lack of counter-cannula and stylet. CONCLUSIONS: In view of the high proportion of major complications, TLT using the presently available kit is unsuitable for major head and neck surgery. However, the considerable advantages of the technique would recommend it as a valid alternative to surgical tracheotomy if the kit included a counter-cannula and stylet.

Clinical Competence↗
PubMed2000

Site-directed mutagenesis of human ceruloplasmin:. production of a proteolytically stable protein and structure-activity relationships of type 1 sites.

A fully active recombinant human ceruloplasmin was obtained, and it was mutated to produce a ceruloplasmin stable to proteolysis. The stable ceruloplasmin was further mutated to perturb the environment of copper at the type 1 copper sites in two different domains. The wild type and the mutated ceruloplasmin were produced in the yeast Pichia pastoris and characterized. The mutations R481A, R701A, and K887A were at the proteolytic sites, did not alter the enzymatic activity, and were all necessary to protect ceruloplasmin from degradation. The mutation L329M was at the tricoordinate type 1 site of the domain 2 and was ineffective to induce modifications of the spectroscopic and catalytic properties of ceruloplasmin, supporting the hypothesis that this site is reduced and locked in a rigid frame. In contrast the mutation C1021S at the type 1 site of domain 6 substantially altered the molecular properties of the protein, leaving a small fraction endowed with oxidase activity. This result, while indicating the importance of this site in stabilizing the overall protein structure, suggests that another type 1 site is competent for dioxygen reduction. During the expression of ceruloplasmin, the yeast maintained a high level of Fet3 that was released from membranes of yeast not harboring the ceruloplasmin gene. This indicates that expression of ceruloplasmin induces a state of iron deficiency in yeast because the ferric iron produced in the medium by its ferroxidase activity is not available for the uptake.

Amino Acid Sequence↗
PubMed2000

Thalidomide: current and potential clinical applications.

More than three decades after its withdrawal from the world marketplace, thalidomide is attracting growing interest because of its reported immunomodulatory and anti-inflammatory properties. Current evidence indicates that thalidomide reduces the activity of the inflammatory cytokine tumor necrosis factor (TNF)-alpha by accelerating the degradation of its messenger RNA. Thalidomide also inhibits angiogenesis. Recently, the drug was approved for sale in the United States for the treatment of erythema nodosum leprosum, an inflammatory complication of Hansen's disease. However, it has long been used successfully in several other dermatologic disorders, including aphthous stomatitis, Behçet's syndrome, chronic cutaneous systemic lupus erythematosus, and graft-versus-host disease, the apparent shared characteristic of which is immune dysregulation. Many recent studies have evaluated thalidomide in patients with human immunodeficiency virus (HIV) infection; the drug is efficacious against oral aphthous ulcers, HIV-associated wasting syndrome, HIV-related diarrhea, and Kaposi's sarcoma. To prevent teratogenicity, a comprehensive program has been established to control access to the drug, including registration of prescribing physicians, dispensing pharmacies, and patients; mandatory informed consent and education procedures; and limitation of the quantity of drug dispensed. Clinical and, in some patients, electrophysiologic monitoring for peripheral neuropathy is indicated with thalidomide therapy. Other adverse effects include sedation and constipation. With appropriate safeguards, thalidomide may benefit patients with a broad variety of disorders for which existing treatments are inadequate.

Angiogenesis Inhibitors↗