Biomedical subjects

D Donati

Publications and source records attributed to D Donati.

At least 19 recordsLinked to original sources

PubMed2006

Human herpesvirus-6B active infection associated with relapsing bilateral anterior optic neuritis.

BACKGROUND AND OBJECTIVES: Human herpesvirus-6 (HHV-6) is the causative agent of exanthem subitum. Both HHV-6 variants, A and B, have been associated with central nervous system (CNS) diseases, suggesting a wide neuropathogenic potential. We describe a case of recurrent bilateral anterior optic neuritis with HHV-6 active infection associated with clinical relapses. CASE REPORT: A 23-year old woman presented with progressive visual impairment, bilateral papillitis and painful ocular movements. Nested polymerase chain reaction (PCR) for DNA viruses, HHV-6 variant specific real time quantitative PCR, serological analysis and retrotranscription PCR (RT-PCR) for HHV-6 mRNA transcripts were performed. Nested PCR in PBMC and CSF samples was negative for all viruses but positive for HHV-6 DNA, subtyped as HHV-6B. The disease had a relapsing/remitting course. During relapses PBMC samples remained positive for HHV-6 DNA, and HHV-6 active infection was confirmed by the presence of anti-HHV-6 IgM and of HHV-6 U27 mRNA transcript. High viremia levels and relapses were overlapping. After the last relapse, the patient was successfully treated with gancyclovir. CONCLUSIONS: The case reported here suggests a possible association of HHV-6 in bilateral optic neuritis. HHV-6 could be monitored when bilateral optic neuritis is identified, in order to establish an appropriate antiviral therapy.

Adult↗

PubMed2006

Evaluation of ex vivo expanded human NK cells on antileukemia activity in SCID-beige mice.

The possibility of using natural killer (NK) cells in treatment of human hematological malignancies has increased in recent years. One factor contributing to this is the introduction of new methods for ex vivo generation of enriched populations of clinical grade NK cells. The objective of the present study was to evaluate the safety and efficacy of human ex vivo expanded clinical grade NK cells against K562 leukemia cells in severe combined immunodeficiency disease (SCID)-beige mice. Irradiated SCID-beige mice were injected intravenously (i.v.) with K562 leukemia cells. Following leukemia cell injection, mice were injected with ex vivo expanded human NK cells. NK cells were followed in vivo and mice monitored for survival from leukemia. Administration of these ex vivo expanded clinical grade NK cells was safe and prevented leukemia development. In conclusion, these results imply possibilities for the use of this NK cell preparation in treatment trials of human hematological malignancies and possibly other forms of cancer.

Animals↗

PubMed2006

Tacrolimus combined with two different dosages of sirolimus in kidney transplantation: results of a multicenter study.

Tacrolimus combined with mycophenolate mofetil (MMF) is an effective regimen in kidney transplantation. This study compared the efficacy of combining tacrolimus and two different dosages of sirolimus with an established tacrolimus-MMF regimen. Each day in addition to tacrolimus, 325 patients received 2 mg sirolimus (TAC-SRL2 mg), 325 patients received 0.5 mg sirolimus (TAC-SRL0.5 mg) and 327 patients 1 g MMF (TAC-MMF). The initial tacrolimus dose was 0.2 mg/kg/day. Sirolimus patients received loading doses of 6 or 1.5 mg, and daily doses of 2 or 0.5 mg thereafter. Steroid administration was identical for all groups. The incidence of biopsy-proven acute rejection was lower in the TAC-SRL2 mg group (15.7%) compared with the TAC-SRL0.5 mg (25.2%, p = 0.003) and the TAC-MMF groups (22.3%, p = 0.036). Six-month graft survival was 91.0% (TAC-SRL2 mg), 92.6% (TAC-SRL0.5 mg) and 92.4% (TAC-MMF); the respective values for patient survival were 98.1%, 97.8% and 97.9%. Thirty-four patients (10.5%), 19 patients (5.8%) and 16 patients (4.9%) in the TAC-SRL2 mg, TAC-SRL0.5 mg and TAC-MMF groups, respectively, discontinued the study because of adverse events. Hyperlipemia was reported more often in the TAC-SRL2 mg group (24.0%) compared with 19.4% (TAC-SRL0.5 mg) and 11.0% (TAC-MMF; p < 0.05). Combining 2 mg sirolimus/day with tacrolimus results in lower rates of acute rejection, but a higher incidence of adverse events.

Adult↗

PubMed2005

Substituted tetraazaacenaphthylenes as potent CRF1 receptor antagonists for the treatment of depression and anxiety.

Two isomers of the hexahydro-tetraazaacenaphthylene templates (1 and 2) are presented as novel, potent, and selective corticotropin releasing factor-1 (CRF1) receptor antagonists. In this paper, we report the affinity and SAR of a series of compounds, as well as pharmacokinetic characterization of a chosen set. The anxiolitic activity of a selected example (2ba) in the rat pup vocalization model is also presented.

Acenaphthenes↗

PubMed2005

Osteoarticular allograft reconstruction of the distal radius after bone tumour resection.

Resection of the distal end of the radius is indicated in the treatment of locally aggressive primary benign and malignant bone tumours. The aim of this study was to evaluate the technique of osteoarticular allograft reconstruction of this bone defect. We analysed 12 patients retrospectively with a minimum follow-up of 2 years (range 26-145 months, median 52 months). Three patients had a malignant tumour and nine had a giant cell tumour. The patients ages ranged from 13 to 65 years. The mean resected length of the radius was 6.6 (range 4-14)cm. Non-union of the osteotomy line was diagnosed 6 months after surgery in one case and needed bone grafting. Distal radio-ulnar joint instability was observed in eight cases. Subchondral bone alterations and joint narrowing were present in all cases but were painful in only one patient. The mean range of motion was 51 degrees of flexion and 37 degrees of extension.

Adolescent↗

PubMed2005

A randomized trial of steroid avoidance in renal transplant patients treated with everolimus and cyclosporine.

In this randomized trial renal transplant recipients were treated with basiliximab, everolimus 3 mg/day, low-dose CsA. At transplantation, patients were randomized to stop steroids at the seventh day (group A) or to continue oral steroids in low doses (group B). Of the 113 patients enrolled, 65 were randomized to group A and 68 to group B. All patients were followed for 2 years. During the study 28 (43%) group A patients required reintroduced corticosteroids. One patient died, in group B. The Graft survival rate was 97% in group A and 90% in group B. There were more biopsy-proven rejections in group A (32% vs 16%; P = .044). The mean creatinine clearance was 54 +/- 21 mL/min in group A vs 56 +/- 22 mL/min in group B. Mean levels of serum cholesterol tended to be lower in group A, but the difference was of borderline significance (191 +/- 91 vs 251 +/- 188 mg/dL; P = .07). Vascular thrombosis (0 vs 5) and pneumonia requiring hospitalization (2 vs 7) tended to be more frequent in group B. Only three cases of CMV infection (1 vs 2) occurred. An immunosuppressive therapy with everolimus and low-dose CsA allows one to obtain excellent renal graft survival and stable graft function at 2 years. Early interruption of steroids in patients treated with this regimen may increase the risk of acute rejection, but neither affects graft survival nor graft function, while possibly reducing the risk of hyperlipemia and vascular thrombosis. About 60% of patients given everolimus and low-dose CsA can definitively stop steroids after 1 week.

Adolescent↗

PubMed2005

Blood cyclosporine level soon after kidney transplantation is a major determinant of rejection: insights from the Mycophenolate Steroid-Sparing Trial.

Target organs express antigens directly recognized by antigen-specific T cells, thereby precipitating rejection. When early T-cell activation is inhibited, there is a low risk of rejection. We sought to determine the predictive values of serial posttransplant blood cyclosporine trough (C(0)) concentrations to minimize the risk for a first rejection episode compared with 2-hour postdose (C(2)) drug concentrations. The final aim of the study was to identify a concentration range for the best predictive pharmacokinetic parameter that should be targeted to reduce the risk of rejection. This possibility was explored in 334 de novo kidney transplant recipients who participated in the prospective, multicenter Mycophenolate Steroid-Sparing Trial. Among measurements performed during the first 6 months postsurgery, cyclosporine C(0) levels measured early after transplantation were the strongest predictor of acute graft rejection. Levels within 300 to 440 ng/mL were associated with the lowest risk of rejection, while patients with levels lower than 300 ng/mL showed a more than double risk. Cyclosporine trough values predicted allograft rejection with an accuracy of 74%, while C(2) levels had no predictive value. These findings underline the need to target cyclosporine therapy early posttransplant to modulate T-cell activation.

Adrenal Cortex Hormones↗

PubMed2005

Circulating epstein-barr virus in children living in malaria-endemic areas.

Children living in malaria-endemic regions have high incidence of Burkitt's lymphoma (BL), the aetiology of which involves Plasmodium falciparum malaria and Epstein-Barr virus (EBV) infections. Acute malarial infection impairs the EBV-specific immune responses with the consequent increase in the number of EBV-carrying B cells in the circulation. To further understand the potential influence of malarial infection on the EBV persistence in children living in malaria-endemic areas, we studied the occurrence and quantified cell-free EBV-DNA in plasma from 73 Ghanaian children with and without acute malarial infection. Viral DNA was detected in 40% of the samples (47% in the malaria-infected and 34% in the nonmalaria group) but was absent in plasma from Ghanaian adults and healthy Italian children. These findings provide evidence that viral reactivation is common among children living in malaria-endemic areas, and may contribute to the increased risk for endemic BL. The data also suggest that the epidemiology of EBV infection and persistence varies in different areas of the world.

Burkitt Lymphoma↗

PubMed2005

Surgical treatment and outcome of conventional pelvic chondrosarcoma.

We reviewed 124 patients with a conventional pelvic chondrosarcoma who had been treated over a period of 20 years. We recorded the type of tumour (central or peripheral), type of operation (limb salvage surgery or hemipelvectomy), the grade of tumour, local recurrence and/or metastases, in order to identify the factors which might influence survival. More satisfactory surgical margins were achieved for central tumours or in those patients treated by hemipelvectomy. However, grade 1 tumours, whatever the course, did not develop metastases or cause death, while grade 3 tumours had the worst outcome and prognosis. Central, high-grade tumours require aggressive surgical treatment in order to achieve adequate surgical margins, particularly in those lesions located close to the sacroiliac joint. By contrast, grade 1 peripheral chondrosarcomas may be treated with contaminated margins in order to reduce operative morbidity, but without reducing survival.

Bone Neoplasms↗

PubMed2004

Long-term outcome for patients with non-metastatic Ewing's sarcoma treated with adjuvant and neoadjuvant chemotherapies. 402 patients treated at Rizzoli between 1972 and 1992.

We evaluated the long-term results obtained in 402 patients with non-metastatic Ewing's sarcoma (ES) of the bone treated in a single institution with adjuvant and neoadjuvant chemotherapies between 1972 and 1992. Multivariate analyses showed male gender, age older than 14 years, high serum lactate dehydrogenase (LDH) level, axial location of the tumour, use of radiotherapy alone as a local treatment, and poor histological response to chemotherapy, to be independent, adverse prognostic factors for event-free survival (EFS). At a mean follow-up of about 18 years (10-30 years), 177 patients (44.0%) remained continuously free of disease, 2 died of doxorubicin-induced cardiotoxicity and 8 developed a second neoplasm (5 died, and 3 are alive and free of disease). 215 patients relapsed with metastases and/or local recurrence: 14 are alive and free of disease, 1 is alive with uncontrolled disease, and 200 died. The overall survival (OS) at real follow-ups of 5-, 10-, 15- and 20-years was 57.2, 49.3, 44.9 and 38.4%, respectively. We conclude that since local or systemic relapses, treatment-complications and second malignancies are more common after 5 years or more from the beginning of treatment; a long-term follow-up is mandatory for patients with ES.

Adolescent↗

PubMed2004

Osteosarcoma of the pelvis.

AIMS: To describe the outcomes of a large number of patients with pelvic osteosarcoma, and to define the guidelines for appropriate treatment. METHODS: We reviewed 60 consecutive patients with primary pelvic high-grade osteosarcoma. The tumour involved the whole hemipelvis in 15 cases, while the most common location was the iliac wing in 29 cases (48.3%): 25 of these adjacent to or passing the sacroiliac joint. RESULTS: Thirty patients underwent surgery; there were 16 hindquarter amputations and 14 internal hemipelvectomies. All the patients who presented with metastasis died of their disease. In 18 cases wide margins were achieved, however, eight patients experienced local recurrence. Of the series, only eight patients are still alive. CONCLUSION: The use of intense chemotherapy and surgical wide margin, hardly seems to achieve local control, however, tumour necrosis was correlated with positive prognosis. When internal hemipelvectomy it is not safe enough, amputation must be considered, particularly for cases with sacrifice of the sciatic nerve roots or for older patients where a shorter surgical procedure can be less risky.

Adolescent↗

PubMed2004

[Gait analysis after rotationplasty hip surgery for malignant tumor of the proximal femur].

Rotationplasty of the hip joint is a special surgical technique used for the treatment of malignant tumors of the proximal part of the femur. We report a clinical case and gait analysis results before and after rehabilitation training. Evaluation of joint motion, kinetic moments, and the electromyographic findings enabled us to document progressive adaptation of muscle and joint function to their new role in the motor pattern, demonstrating the exceptional strength of rotationplasty. Active control of two fulcrums in the lower limb, the pseudo hip proximally and the pseudo knee intermedially, makes this type of operation extremely advantageous compared to the alternative of hip disarticulation or hemipelvectomy. Total absence of pain together with the preservation of articular and cutaneous proprioception are important advantages. Rotationplasty is an attractive alternative for treatment of malignant tumors of the proximal part of the femur.

Child↗

PubMed2003

Detection of human herpesvirus-6 in mesial temporal lobe epilepsy surgical brain resections.

BACKGROUND: Human herpesvirus-6 (HHV-6), a ubiquitous beta-herpesvirus, is the causative agent of roseola infantum and has been associated with a number of neurologic disorders including seizures, encephalitis/meningitis, and multiple sclerosis. Although the role of HHV-6 in human CNS disease remains to be fully defined, a number of studies have suggested that the CNS can be a site for persistent HHV-6 infection. OBJECTIVE: To characterize the extent and distribution of HHV-6 in human glial cells from surgical brain resections of patients with mesial temporal lobe epilepsy (MTLE). METHOD: Brain samples from eight patients with MTLE and seven patients with neocortical epilepsy (NE) undergoing surgical resection were quantitatively analyzed for the presence of HHV-6 DNA using a virus-specific real-time PCR assay. HHV-6 expression was also characterized by western blot analysis and in situ immunohistochemistry (IHC). In addition, HHV-6-reactive cells were analyzed for expression of glial fibrillary acidic protein (GFAP) by double immunofluorescence. RESULTS: DNA obtained from four of eight patients with MTLE had significantly elevated levels of HHV-6 as quantified by real-time PCR. HHV-6 was not amplified in any of the seven patients with NE undergoing surgery. The highest levels of HHV-6 were demonstrated in hippocampal sections (up to 23,079 copies/10(6) cells) and subtyped as HHV-6B. Expression of HHV-6 was confirmed by western blot analysis and IHC. HHV-6 was co-localized to GFAP-positive cells that morphologically appeared to be astrocytes. CONCLUSIONS: HHV-6B is present in brain specimens from a subset of patients with MTLE and localized to astrocytes in the absence of inflammation. The amplification of HHV-6 from hippocampal and temporal lobe astrocytes of MTLE warrants further investigation into the possible role of HHV-6 in the development of MTLE.

Adolescent↗

PubMed2003

Neoadjuvant chemotherapy for osteosarcoma of the extremities with metastases at presentation: recent experience at the Rizzoli Institute in 57 patients treated with cisplatin, doxorubicin, and a high dose of methotrexate and ifosfamide.

BACKGROUND: Effective adjuvant or neoadjuvant regimens of chemotherapy have dramatically improved the prognosis of patients with high-grade osteosarcoma of the extremity, localized at diagnosis. Currently, little is known about patients with metastatic disease at presentation. PATIENTS AND METHODS: From May 1995 to May 2000, 57 patients with osteosarcoma of the extremity, metastatic at presentation, were treated according to the following scheme: primary chemotherapy, restaging, simultaneous resection of primary tumor and metastatic lesions, and maintenance chemotherapy. RESULTS: Thirty-five patients achieved remission. At a follow-up ranging from 2 to 7 years, seven remained continuously free of disease, one died of chemotherapy-related toxicity and 27 patients relapsed. Twenty-one of the 22 patients who never achieved remission died as a result of the tumor, as well as 20 of the 27 who achieved remission but then relapsed. Of the remaining seven relapsing patients, six are alive with uncontrolled disease, while one is alive and free of disease 24 months after the last post-relapse treatment. Two-year event-free survival (EFS) and overall survival (OS) were 21% and 55%, respectively. These results are significantly poorer than those achieved in 128 contemporary patients with non-metastatic disease at presentation, treated with the same chemotherapy protocol (2-year EFS and OS of 75% and 94%, respectively). CONCLUSIONS: The results of our study confirm that the prognosis of patients with osteosarcoma of the extremity, metastatic at presentation, remains poor, despite the use of aggressive treatments.

Adolescent↗

PubMed2003

Therapy and survival after recurrence of Ewing's tumors: the Rizzoli experience in 195 patients treated with adjuvant and neoadjuvant chemotherapy from 1979 to 1997.

BACKGROUND: Many papers have reported the results achieved with combined therapy for Ewing's tumors, but little is known about the treatment and outcome of those 30-40% of patients who relapse. PATIENTS AND METHODS: In a retrospective study, we evaluated 195 patients with Ewing's tumors treated at our institution from 1979 to 1997 with chemotherapy, radiotherapy, surgery or combined therapies after recurrence. RESULTS: A second complete remission was achieved in only 26 patients (13.3%); 12 relapsed again and died of the tumor. The 5-year post-relapse event-free survival and overall survival were 9.7% and 13.8%, respectively; both of which were significantly better for patients who had relapsed >/=2 years after the beginning of the first treatment (14.3% versus 2.5%; P <0.001) and for patients who relapsed with only lung metastases (14.5% versus 0.9%; P <0.0005). In terms of treatment, patients treated with surgery or radiotherapy, alone or in combination with chemotherapy, had better survival rates than patients treated with chemotherapy alone (15.4% versus 0.9%; P <0.0001). CONCLUSIONS: The outcome of Ewing's tumor patients who relapse after combined treatment is very poor. However, these patients may be divided into two groups: those that can be cured with traditional treatments (late relapse and/or only lung metastases), and a second group of patients (early relapses with metastases in lungs and/or other sites) who gain no benefit from traditional therapies. For the latter group, multicenter studies are needed to evaluate new strategies of treatment.

Adolescent↗

PubMed2003

Local and systemic control in Ewing's sarcoma of the femur treated with chemotherapy, and locally by radiotherapy and/or surgery.

The role of radiotherapy and/or surgery in the local treatment of Ewing's sarcoma has still to be determined. The outcome of Ewing's sarcoma may differ according to its location and a selection bias towards surgery limits the ability to compare methods of local treatment. We have carried out a retrospective review of 91 consecutive patients treated for non-metastatic Ewing's sarcoma of the femur. They received chemotherapy according to four different protocols. The primary lesion was treated by surgery alone (54 patients), surgery and radiotherapy (13) and radiotherapy alone (23). One was treated by chemotherapy alone. At a median follow-up of ten years, 48 patients (53%) remain free from disease, 39 (43%) have relapsed, two (2%) have died from chemotherapeutic toxicity and two (2%) have developed a radio-induced second tumour. The probability of survival without local recurrence was significantly (p = 0.01) higher in patients who were treated by surgery with or without radiotherapy (88%) than for patients who received radiotherapy alone (59%). The five- and ten-year overall survival rates were 64% and 57%, respectively. Patients who were treated by surgery, with or without radiotherapy, had a five- and ten-year overall survival of 64%. Patients who received only radiotherapy had a five- and ten-year survival of 57% and 44%, respectively. Our results indicate that in patients with Ewing's sarcoma of the femur, better local control is achieved by surgical treatment (with or without radiotherapy) compared with the use of radiotherapy alone. Further studies are needed to verify the impact of this strategy on overall survival.

Adolescent↗

PubMed2003

The role of lymphadenectomy in gastric cancer in elderly patients.

The incidence of gastric cancer in elderly patients has significantly increased in the last few decades. Recent reports show that resective surgical procedures are the best therapeutic treatment for aged patients without important pre-existing clinical disorders. The role of lymphadenectomy in elderly patients with gastric cancer is not clear. The present study analyses literature data regarding the optimal extension of lymphadenectomy in gastric carcinoma; we reviewed the data from Japanese authors and from newer multicentric prospective European studies (German Gastric Carcinoma Study Group, Dutch Gastric Cancer Group, Medical Research Council, Italian Gastric Cancer Study Group). We also analysed the clinicopathological characteristics, the site, the symptoms, the spread and recurrence patterns of gastric carcinoma in the elderly compared with adult patients. This review shows that 75-90% of the diagnosis of gastric carcinoma in aged patients is done in advanced stage and an aggressive surgical treatment is required. A pre-existing illness and the ASA stage of the patients are directly correlated to postoperative complications. For these reasons, considering the clinicopathological features of the disease, a curative surgical operation using also an extended lymph node dissection is recommended for aged patients in good health.

Aged↗

PubMed2002

Knee arthrodesis with a temporary spacer performed in malignant tumor around the knee.

The issue of utilizing a temporary cement spacer after a knee resection arthrodesis of a highly malignant bone tumor is discussed. In our experience, this is the first type of reconstruction performed in the early days of the limb salvage. Now, after more than 12 years of follow-up based on the results of 84 patients, the usefulness and mechanical performance of this type of reconstruction are considered. Of these patients, 45 died of disease. Wound complications were present in 31% of the patients and led to amputation in 7 and healing failure in 6. Mechanical complications occurred in 39%, but radiographic analysis of the implant showed 32 cases (38%) with an inadequate spacer. Only 9 patients are still walking on the original reconstruction, 6 of them uncomplicated (the remaining 3 had rod migrations and shortening). The survival curve showed no statistical difference between the two groups (adequate vs inadequate spacer). In 33 patients who are still alive and retain their limb, the final functional results were excellent in 6, good in 8, fair in 14, and poor in 5. This type of reconstruction can still be considered in developing countries, or when a definitive arthrodesis is planned where there is a lack of a bone source (children, no bone bank). In our institution, reconstruction with cement is still suggested for patients with a large tumor around the knee, when the quadriceps is completely sacrificed, and the patient prognosis is markedly unfavorable.

Adolescent↗