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Biomedical subjects

D Donati

Publications and source records attributed to D Donati.

At least 73 records · Page 4Linked to original sources

Peripheral neuropathy associated with anti-myelin basic protein antibodies in a woman vaccinated with rubella virus vaccine.

Active immunisation with rubella vaccine has not been commonly associated with neurological complications. We report the case of a 23-year-old woman who developed a mild, distal demyelinating neuropathy after immunisation with the live attenuated RA 27/3 rubella strain. Post-immunisation immunologic studies carried over 24 months showed the presence of antibodies to the RV proteins, particularly to the capsid antigen, and to the myelin basic protein (MBP). A similarity between a C antigen motif and a sequence of the MBP was found by computer analysis. The cross-reactivity was confirmed by immunising mice with a synthetic peptide derived from the MBP, which developed a strong humoral response to RV and MBP. This finding raises the possibility that a virus-induced immune response could lead to an autoaggressive reaction responsible for demyelination.

Adult↗

Angiogenesis in lipoma: An experimental study in the chick embryo chorioallantoic membrane.

Lipoma is one of the most common benign mesenchymal tumors. Its ability to trigger an angiogenic response is a critical step for its growth. Because adipose tissue serves as an important conduit for the vasculature, it is conceivable that the angiogenic properties of this tissue may modulate the growth of the vasculature in a paracrine manner. We investigated in vivo the angiogenic potential of bioptic fragments of human lipoma by using the chick embryo chorioallantoic membrane (CAM), a useful model for such an investigation. The angiogenic response in pathological and control implants was assessed on histologic sections by a morphometric method, 96 h after grafting. Results showed that pathological samples were surrounded by numerous allantoic vessels with a radially arranged pattern around the implant. The vascular counts in the CAMs treated with lipoma implants were comparable to that of FGF-2. The role played in vasoproliferative response by angiogenic cytokines (FGF-2, VEGF) released by adipocytes, by endogenous cytokines, such as FGF-2, stored in the CAM extracellular matrix and by angiogenic growth factors released by perivascular mononuclear cells around the newly-formed blood vessels, were supported by this study.

Adult↗

Expression of inducible lymphocyte costimulatory molecules in human renal allograft.

BACKGROUND: CTLA-4/CD28-B7 and CD40-CD40L interactions constitute two key costimulatory pathways in lymphocyte signalling during experimental allograft rejection. Studies on the expression of these molecules in human transplant rejection are still lacking. METHODS: The immunohistochemical study was performed on renal biopsies obtained for various clinical complications from 25 renal transplant patients. Expression of B7-1 and B7-2 and their counter-receptor CTLA-4, and of CD40 and its counter-receptor CD40L was examined. RESULTS: In acute rejection a focal intense infiltration of B7-1+ and B7-2+ cells (mainly CD20- CD14+) and of CTLA-4+ T lymphocytes (mainly CD8+) was present. In contrast, CD40 and CD40L were rarely expressed. Accumulations of T lymphocytes were found in the interstitium in the same area containing B7-1+ and B7-2+ cells. The scattered CD40L+ cells found in the T-cell infiltrate exhibited the CD4+ phenotype. In chronic rejection only a few B7-1+, B7-2+ or CTLA-4+ cells were detectable. In contrast, several CD40L+CD4+ cells were present both in the interstitium and in glomeruli. Moreover, an intense expression of CD40 on the endothelium was observed. In patients with cyclosporin nephrotoxicity cells positive for B7-1, B7 2, CTLA-4, CD40, or CD40L were absent. CONCLUSIONS: These results demonstrate a differential expression of costimulatory molecules in renal biopsies of allograft recipients undergoing acute or chronic rejection. Moreover, their detection may prove useful to discriminate rejection from cyclosporin nephrotoxicity.

Abatacept↗

The use of antibiotic-impregnated cement in infected reconstructions after resection for bone tumours.

We have studied 35 patients with infected reconstructions after segmental resection for bone tumours. Two different regimes of treatment were employed both of which entailed debridement and the use of cement impregnated with antibiotic. In 25 patients gentamicin-PMMA beads were used and in ten an antibiotic-impregnated cement spacer. Better results were achieved with the second procedure in terms of cases healed, the number of operations, time of healing, time of recovery and the functional score. The use of vancomycin in the cement spacer gave better local control.

Adolescent↗

Brief communication: criterion validity of the Personality Diagnostic Questionnaire-4+ (PDQ-4+) in a mixed psychiatric sample.

Three hundred consecutively admitted in- and outpatients were administered the Personality Diagnostic Questionnaire-4+ (PDQ-4+). The Structured Clinical Interview for DSM-IV Axis II Personality Disorders, Version 2.0 (SCID-II) was used as the external diagnostic standard for personality disorder (PD) assessment. SCID-II was administered blind to PDQ-4+ scores. Low agreement between PDQ-4+ and SCID-II was observed for both dimensional and categorical PD evaluations. Receiver operating characteristic (ROC) analysis showed a definitively satisfactory discriminatory capability only for two PDQ-4+ PD scales (dependent, and antisocial). In agreement with previous studies, these results showed that PDQ-4+ was not a substitute for a structured diagnostic interview.

Adult↗

Serological diagnosis of respiratory viral infections. A five-year study of hospitalised patients.

The results of a five-year study of paired sera from 410 hospitalised patients-mainly children-with respiratory illness are reported. Samples were divided into groups based on clinical diagnosis. The data of each group were analysed in relation to patient age (under or over 1 year of age). The percentage of positive serological diagnoses ranged from 29.4% in the respiratory viral illness group to 46.2% in the bronchiolitis group. Each group showed a prevalent serological diagnosis. Respiratory viral illness patients over 1 year were diagnosed mainly with Influenza virus infection (73.8% positive diagnosis), pharyngotonsillitis patients with Adenovirus infection (72.2%), laryngitis patients with Parainfluenza virus infection (100%), pneumonia patients with Mycoplasma pneumoniae infection (56.7%), and bronchiolitis patients with Respiratory Syncytial virus infection (100%). The serological diagnosis patterns of each group or subgroup were statistically significant with respect to the other groups (chi 2 or Fisher exact tests). Unlike previous reports, none of the patients under 1 year in our study was diagnosed with Influenza virus infection or Parainfluenza virus type 3. Conversely, Respiratory Syncytial virus infection data were in line with previous reports, being the most frequently diagnosed infection in the bronchiolitis group and in the subgroups of patients under 1 year of age. The present report provides new information on patterns of respiratory infections.

Adenoviridae↗

Substituted indole-2-carboxylates as in vivo potent antagonists acting as the strychnine-insensitive glycine binding site.

A series of indole-2-carboxylates bearing suitable chains at the C-3 position of the indole nucleus was synthesized and evaluated in terms of in vitro affinity using [3H]glycine binding assay and in vivo potency by inhibition of convulsions induced by N-methyl-D-aspartate (NMDA) in mice. 3-[2-[(Phenylamino)carbonyl]ethenyl]-4,6-dichloroindole-2-carboxyl ic acid (8) was an antagonist at the strychnine-insensitive glycine binding site (noncompetitive inhibition of the binding of [3H]TCP, pA2 = 8.1) displaying nanomolar affinity for the glycine binding site (pKi = 8.5), coupled with high glutamate receptor selectivity (> 1000-fold relative to the affinity at the NMDA, AMPA, and kainate binding sites). This indole derivative inhibited convulsions induced by NMDA in mice, when administered by both iv and po routes (ED50 = 0.06 and 6 mg/kg, respectively). The effect of the substituents on the terminal phenyl ring of the C-3 side chain was investigated. QSAR analysis suggested that the pKi value decreases with lipophilicity and steric bulk of substituents and increases with the electron donor resonance effect of the groups present in the para position of the terminal phenyl ring. According to these results the terminal phenyl ring of the C-3 side chain should lie in a nonhydrophobic pocket of limited size, refining the proposed pharmacophore model of the glycine binding site associated with the NMDA receptor.

Animals↗

Osteogenic sarcoma of the extremity with detectable lung metastases at presentation. Results of treatment of 23 patients with chemotherapy followed by simultaneous resection of primary and metastatic lesions.

BACKGROUND: In the past 20 years, it has been demonstrated that the combination of surgery and chemotherapy improves the prognosis for patients with osteosarcoma of the extremity without detectable metastases at presentation. By contrast, the efficacy of chemotherapy coupled with aggressive surgery has not yet been well established for patients with metastatic disease at diagnosis. The current study evaluates the efficacy of chemotherapy associated with simultaneous surgery of primary and metastatic lesions in patients presenting with osteosarcoma of the extremity with lung metastases. METHODS: Patients with lung metastases originating from an osteosarcoma of the extremity received chemotherapy (high dose methotrexate, cisplatin, doxorubicin, and ifosfamide) followed by simultaneous resection of primary and metastatic lesions and additional chemotherapy. RESULTS: Between January 1993 and June 1995, 23 patients entered the study. After primary chemotherapy, lung metastases disappeared in three patients, whereas in four patients they remained surgically unresectable. All seven patients received surgical treatment of the primary tumor only. In the remaining 16 patients, a simultaneous resection of the primary and metastatic tumors was performed after chemotherapy. The resection of metastatic lesions resulted in a complete remission in 15 patients and an incomplete remission in 1 patient. All five patients who never achieved tumor free status died within a few months. Of the 18 patients who achieved radiologic remission at a 30-month follow-up (range, 14-50 months), 10 (55.5%) remained continuously free of disease, 7 relapsed with new metastases, and 1 died of toxicity. In 13 of the 18 patients who underwent a complete simultaneous resection of the primary and the metastatic lesions, or whose pulmonary metastases disappeared after chemotherapy, a strong correlation was found between degree of necrosis of the primary tumor and of the metastatic tumor. CONCLUSIONS: In patients presenting with osteosarcoma of the extremity with lung metastases, the combination of aggressive chemotherapy with simultaneous resection of the primary and metastatic lesions improves traditionally negative outcomes. The strong correlation found between the histologic response of the primary and metastatic tumors supports the strategy, largely used currently in the neoadjuvant treatment of osteosarcoma, of tailoring postoperative chemotherapy on the basis of the histologic response of the primary tumor to preoperative chemotherapy.

Adolescent↗

Interleukin-1 receptors and receptor antagonist in haemodialysis.

BACKGROUND: Biological activity of interleukin-1 (IL-1) depends on the number and type of IL-1 receptors on target cells and on the amounts of its naturally occurring inhibitor, the IL-1 receptor antagonist (IL-1ra). METHODS: Expression of IL-1 receptor was studied on the peripheral blood mononuclear cells of 20 end-stage renal-disease patients maintained by chronic haemodialysis by means of either polysulphone (10 patients) or cuprophane membranes (10 patients) and compared to that of normal controls. Plasma and cellular levels of IL-1ra and IL-1 beta were also measured. RESULTS: The proportion of monocytes expressing the IL-1 receptor was strikingly higher in haemodialysis patients than in the healthy population. This proportion further increased during haemodialysis with cuprophane but not with polysulphone. Expression of the IL-1 receptor on lymphocytes was very low in both controls and dialysed patients; in the latter there was no intradialytic variation. Plasma concentrations of IL-1 beta and IL-1ra were elevated in haemodialysis patients and undetectable in controls. Whereas plasma IL-1 beta decreased throughout haemodialysis, IL-1ra further increased, with no significant differences between the two membranes used. Total cellular IL-1 beta and IL-1ra were also higher in the patient group than in the healthy controls. A further increase of both IL-1 beta and IL-1ra was detected at the end of the haemodialysis session with any membrane. CONCLUSIONS: Monocytes of haemodialysis patients circulate in a state of activation, which makes them both producer and target of IL-1. Thus there is an autocrine upregulation of IL-1 production. Although IL-1ra levels are high, they are most likely to be expression of monocyte activation rather than represent effective inhibitors of IL-1 activity.

Adult↗

Double-blind, multicenter, randomized trial to compare the effect of two doses of adrenocorticotropic hormone versus placebo in controlling delayed emesis after high-dose cisplatin in adult patients with cancer.

PURPOSE: To compare, in a double-blind, placebo-controlled, randomized trial, the efficacy of two different doses of the depot formulation of adrenocorticotropic hormone (ACTH) in controlling delayed emesis after cisplatin. PATIENTS AND METHODS: One hundred fifty-two patients were enrolled onto the study. On day 1, all patients received cisplatin (60 to 120 mg/m2) and a combination of dexamethasone 20 mg plus ondansetron or metoclopramide to prevent acute emesis. On day 2 (24 hours after cisplatin administration), patients were randomized to receive placebo, or ACTH 1 mg intramuscularly (I.M.), or ACTH 2 mg I.M. plus one additional dose of 1 mg on day 4. Details of vomiting, nausea, and adverse effects were recorded daily for every 24-hour period from day 2 to day 6. In a subset of patients, serum cortisol levels were measured between 20 and 72 hours after cisplatin administration. RESULTS: One hundred fifty patients were assessable. Over the 5 days of the study, delayed vomiting occurred less frequently in the patients treated with ACTH 2 mg plus 1 mg than in those treated with ACTH 1 mg or placebo (28%, 38%, and 65%, respectively; P = .001). The greatest observed differences were seen on days 2 (24 to 48 hours; P = .01) and 3 (48 to 72 hours; P = .01). On days 4, 5, and 6 (96 to 144 hours), no significant differences were observed among the three arms. The severity of delayed emesis expressed as the mean number of emetic episodes per day was 0.48, 0.70, and 0.80, respectively (P = .002). Patients treated with the higher dose of ACTH had the least nausea on day 3 (P = .02) and day 4 (P = .03). Adrenal cortisol secretion rapidly increased after ACTH injection, but was suppressed for approximately 44 hours in the placebo group. Toxicity was mild and transient in all groups. CONCLUSION: ACTH reduces the incidence and severity of delayed vomiting and nausea after cisplatin. A dose of 2 mg 24 hours after cisplatin is better than one of 1 mg. Whether the activity of ACTH is mediated only by adrenal corticosteroids needs to be verified.

Adrenocorticotropic Hormone↗

Synchronous multifocal osteosarcoma: results in twelve patients treated with neoadjuvant chemotherapy and simultaneous resection of all involved bones.

BACKGROUND: Multifocal osteosarcoma is a rare type of tumor which is always excluded from therapy trials and is therefore rarely investigated for prognosis and treatment. PATIENTS AND METHODS: Twelve patients with synchronous multifocal osteosarcoma underwent neoadjuvant chemotherapy and, when feasible, simultaneous resection of involved bones. RESULTS: Four patients were unsuitable for resection and died 5-13 months (average 9 months) later. In eight patients all lesions were resected simultaneously. Four patients are disease-free at 15, 20, 24, and 60 months (average 29 months), and four relapsed and died at 12, 24, 30 and 36 months (average 30.5 months). CONCLUSIONS: Chemotherapy associated with aggressive surgery may be useful. The histological response of different lesions in the same patient are strongly correlated, confirming that synchronous multifocal osteosarcoma is not originally multicentric but unicentric with bone metastases.

Adolescent↗