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Biomedical subjects

L Simoncini

Publications and source records attributed to L Simoncini.

At least 19 recordsLinked to original sources
PubMed2000

High levels of Epstein-Barr virus DNA in blood of solid-organ transplant recipients and their value in predicting posttransplant lymphoproliferative disorders.

Epstein-Barr virus (EBV) DNA was quantitated in peripheral blood mononuclear cells (PBMC) from 25 healthy subjects, 105 asymptomatic solid-organ transplant (SOT) recipients, and 15 SOT recipients with symptomatic EBV infections by using a newly developed quantitative-PCR technique. Patients with symptomatic EBV infections had significantly higher (P < 0.001) median EBV DNA levels than asymptomatic SOT recipients and immunocompetent individuals. In SOT recipients, the positive predictive value of EBV DNA levels of >1, 000 genome equivalents (GE)/0.5 microg of total PBMC DNA was 64.7% for symptomatic EBV infection, while the negative predictive value was 96.1%. In 19 of 32 (59.3%) asymptomatic SOT recipients, EBV DNA levels were consistently below 1,000 GE for as long as 18 months, while 10 of 32 (31.2%) patients had 1,000 to 5,000 EBV GE at least once during follow-up. In a minority of patients (3 of 32; 9.3%), >/=5,000 GE could be detected at least once during follow-up. Reduction of immunosuppressive treatment decreased EBV DNA levels by >/=1 log(10) unit in patients with symptomatic EBV infections. Quantification of EBV DNA is valuable for the diagnosis and monitoring of symptomatic EBV infections in SOT recipients.

Adolescent↗
PubMed2000

Muscle performance about the knee joint in patients who had distal femoral replacement after resection of a bone tumor. An objective study with use of gait analysis.

BACKGROUND: The treatment of a malignant bone tumor in the distal aspect of the femur often requires great sacrifice of bone and muscle. The extent of quadriceps removal has been reported to influence the long-term functional efficiency of a patient's gait. The objective of the present study was to determine gait function as it relates to the residual quadriceps strength and to the specific component or components of the quadriceps removed in patients treated with total knee replacement because of a malignant bone tumor in the distal aspect of the femur. METHODS: Sixteen patients were evaluated after implantation of a modular hinged cementless knee prosthesis. The patients were assigned to two groups on the basis of the different components of the quadriceps muscle that were resected. Group 1 consisted of five patients who had removal of the vastus medialis and the vastus intermedius and two who had removal of the vastus medialis only. Group 2 consisted of nine patients who had removal of the vastus lateralis and the vastus intermedius. Residual muscular strength about the treated knee was measured by voluntary maximum contraction isometric testing. Foot-ground reaction forces, kinematic and kinetic findings, and electromyographic activity during free-speed walking were recorded. RESULTS: The kinematic study showed that the patients in Group 1 tended to have a stiff-knee gait during stance, whereas those in Group 2 (in which the vastus medialis was spared) had a more regular flexion-extension knee pattern. Electromyographic findings showed that a higher percentage of patients in Group 1 had reduced or absent rectus femoris activity during the loading response. Compared with the contralateral side, knee-extension strength in the treated limb was decreased in both groups. However, there were no significant differences between the groups with respect to the pattern of strength loss. CONCLUSIONS: Good gait function can be achieved in patients with a distal femoral tumor that is treated with distal femoral resection, partial excision of the quadriceps, and total knee arthroplasty with insertion of a hinged prosthesis. Patients in whom the vastus lateralis and vastus intermedius were removed had better gait performance and a more physiological knee-loading pattern than did patients in whom the vastus medialis was removed.

Adult↗
PubMed1999

Flat foot functional evaluation using pattern recognition of ground reaction data.

OBJECTIVE: Main purpose of this study was to apply quantitative gait analysis and statistical pattern recognition as clinical decision-making aids in flat foot diagnosis and post-surgery monitoring. DESIGN: Statistical pattern recognition techniques were applied to discriminate between normal and flat foot populations through ground reaction force measurements; ground reaction forces time course was assumed as a sensible index of the foot function. BACKGROUND: Gait analysis is becoming recognized as an important clinical tool in orthopaedics, in pre-surgery planning, post-surgery monitoring and in a posteriori evaluation of different treatment techniques. Statistical pattern recognition techniques have been utilized with success in this field to identify the most significant variables of selected motor functions in different pathologies, and to design classification rules and quantitative evaluation scores. METHODS: Ground reaction forces were recorded during free speed barefoot walks on 28 healthy subjects, and 28 symptomatic flexible flat foot children selected for surgical intervention. A new feature selection algorithm, based on heuristic optimization, was applied to select the most discriminant ground reaction forces time samples. A two-stage pattern recognition system, composed by three linear feature extractors, one for each ground reaction force component, and a linear classifier, was designed to classify the feet of each subject using the selected features. The output of the classifier was used to define a functional score. RESULTS: The classifier assigned the ground reaction force patterns performed by each subject into the right class with an estimated error of 15%, corresponding to an assignment error for each subject's foot of 9%. The most discriminant ground reaction forces time samples selected are in full agreement with the pathophysiology of the symptomatic flexible flat foot. The obtained score was utilized to monitor the 1 and 2 years post-operative functional recovery of two differently treated subgroups of 32 flexible flat foot subjects. CONCLUSIONS: Statistical pattern recognition techniques are promising tools for clinical gait analysis; the obtained score provides important functional information that could be used as a further aid in the clinical evaluation of flat foot and different surgical treatment techniques. RELEVANCE: Symptomatic flexible flat foot surgical decision making is frequently difficult because of the lack of objective criteria to assess functional abnormalities of the foot/ankle complex. Gait analysis and statistical pattern recognition can give us parameters with which to characterize "functional" flat foot. Moreover, we can objectively follow up the recovery of the foot/ankle complex function after surgical treatment.

Algorithms↗
PubMed1999

An anatomically based protocol for the description of foot segment kinematics during gait.

OBJECTIVE: To design a technique for the in vivo description of ankle and other foot joint rotations to be applied in routine functional evaluation using non-invasive stereophotogrammetry. DESIGN: Position and orientation of tibia/fibula, calcaneus, mid-foot, 1st metatarsal and hallux segments were tracked during the stance phase of walking in nine asymptomatic subjects. Rigid clusters of reflective markers were used for foot segment pose estimation. Anatomical landmark calibration was applied for the reconstruction of anatomical landmarks. BACKGROUND: Previous studies have analysed only a limited number of joints or have proposed invasive techniques. METHODS: Anatomical landmark trajectories were reconstructed in the laboratory frame using data from the anatomical calibration procedure. Anatomical co-ordinate frames were defined using the obtained landmark trajectories. Joint co-ordinate systems were used to calculate corresponding joint rotations in all three anatomical planes. RESULTS: The patterns of the joint rotations were highly repeatable within subjects. Consistent patterns between subjects were also exhibited at most of the joints. CONCLUSION: The method proposed enables a detailed description of ankle and other foot joint rotations on an anatomical base. Joint rotations can therefore be expressed in the well-established terminology necessary for their clinical interpretation. RELEVANCE: Functional evaluation of patients affected by foot diseases has recently called for more detailed and non-invasive protocols for the description of foot joint rotations during gait. The proposed method can help clinicians to distinguish between normal and pathological pattern of foot joint rotations, and to quantitatively assess the restoration of normal function after treatment.

Adult↗
PubMed1999

HCV genotyping by three methods: analysis of discordant results based on sequencing.

BACKGROUND: Correct genotyping of hepatitis C virus (HCV) RNA-positive serum samples may have important clinical and therapeutic implications. OBJECTIVES: Three methods were compared to improve accuracy of HCV genotyping. STUDY DESIGN: A panel of 144 HCV RNA-positive sera prospectively tested by a modified Okamoto's type-specific reverse transcription-nested polymerase chain reaction (RT-nPCR) (Okamoto H, Tokita H, Sakamoto M, Kojima M, Iizuka H, Mishiro S. J Gen Virol 1993; 74: 2385-2390) was retrospectively analyzed by two recently described methods which were reported to identify all HCV types and the majority of HCV subtypes: (i) a restriction fragment length polymorphism (RFLP) analysis of PCR products amplified from the 5' untranslated region (5'UTR) of the viral genome (Pohjanpelto P, Lappalainen M, Widell A, Asikainen K, Paunio M. Clin Diagn Virol 1996; 7: 7-16); and (ii) a type-specific RT-nPCR relevant to the core region (Ohno T, Mizokami M, Wu R, Saleh M, Ohba K, Orito E, Mukaide M, Williams R, Lau J. J Clin Microbiol 1997; 35: 201-207). The panel (according to results given by the modified Okamoto's method) consisted of: (i) 105 sera belonging to five different HCV subtypes; (ii) 20 specimens containing a mixture of > or = 2 genotypes; and (iii) 19 untypeable clinical samples. RESULTS: There was agreement of the three methods for 78/144 (54.2%) blood samples, whereas discordant results were obtained for the remaining 66 samples, 56 of which could be typed by sequencing. Of these, 51 (91.7%) were correctly typed by RFLP, 37 (66.0%) by Ohno's and 27 (48.2%) by the modified Okamoto's procedure. The overall genotyping sensitivity of each method over the total number of 134 samples whose genotype was ascertained, was 96.2% for RFLP, 85.8% for Ohno's and 78.3% for the modified Okamoto's procedure. CONCLUSIONS: RFLP analysis, notwithstanding some limitations in subtyping efficiency of genotype 1 samples, appears superior to the two RT-nPCR methods because: (i) it is able to type a larger number of samples; (ii) it is more efficient in identifying genotypes 2a/c, which are widespread in Italy; (iii) it is highly sensitive (together with Ohno's method) in recognizing genotypes 3 and 4.

5' Untranslated Regions↗
PubMed1999

Fludarabine, cyclophosphamide, and dexamethasone (FluCyD) combination is effective in pretreated low-grade non-Hodgkin's lymphoma.

PURPOSE: Fludarabine phosphate is effective as a single agent in low-grade non-Hodgkin's lymphoma (NHL). Combined with other antineoplastic agents it enhances the antitumor effect. Our aim was to define the therapeutic efficacy and toxicity of a combination of fludarabine, cyclophosphamide and dexamethasone (FluCyD) in patients with advanced low-grade lymphoma. PATIENTS AND METHODS: Twenty-five adults with pretreated advanced-stage low-grade NHL were treated with three-day courses of fludarabine 25 mg/m2/day, cyclophosphamide 350 mg/m2/day, and dexamethasone 20 mg/day, every four weeks for a maximum of six courses. RESULTS: Of the 25 patients, 18 (72%) responded, 8 (32%) achieving CR and 10 (40%) PR. Seven were failures. The median follow-up was 21 months (5-26). Eight CR patients remain in CR after 5-21 months. Of 10 PR patients, 3 are in continuous PR without further treatment after 12, 17 and 18 months. Myelosuppression was the most prevalent toxic effect. Although severe granulocytopenia (granulocyte count nadir < 500/microliter) and thrombocytopenia (platelet count nadir < 50,000/microliter) occurred in only 10% and 16% of courses, respectively, slow granulocyte or platelet count recovery caused delay of 40% of the courses. Nine patients (36%) required discontinuation of therapy because of persistent granulocytopenia and/or thrombocytopenia: three after one course, three after 2-4 courses, and three after five courses. Thirteen infectious episodes in 11 patients complicated 11% of courses. Two of 10 patients monitored for the circulating EBV load showed increased viral load. One of these developed aggressive lymphoma. CD4+ lymphocytes declined from a pre-therapy median value of 425/microliter to 141/microliter post-treatment (P = 0.001). Non-hematologic toxicities were rare and mild. CONCLUSIONS: The combination of fludarabine with cyclophosphamide and dexamethasone is effective in pretreated advanced-stage low-grade NHL. It may broaden the range of therapeutic options in the salvage treatment of these patients. The main toxicity of this combination is prolonged myelosuppression that may cause treatment delay or withdrawal. The benefit of adding granulocyte colony-stimulating factor, particularly in patients with poor marrow reserve, needs to be investigated.

Adult↗
PubMed1999

Myoelectric activation pattern during gait in total knee replacement: relationship with kinematics, kinetics, and clinical outcome.

Gait usually presents an excellent improvement after total knee replacement. Nevertheless, some abnormalities persist even after a long period of time. The abnormal knee patterns have been attributed to several possible causes, such as implant geometry and surgical technique, posterior cruciate ligament sparing/sacrificing, preoperative "stiff-knee" pattern due to pain and altered biomechanics, weakness of the extensor muscles, preoperative arthritic pattern, proprioceptive deficiency, and multijoint degenerative involvement. Cocontraction of the knee flexors and extensors is a common strategy adopted to reduce strain and shear forces at the joint, but it increases compressive forces and joint loading. Even in patients with an excellent functional score, the duration of the implant may be compromised by an altered neuromuscular control of the knee. In this paper, we report a single case study carried out over two years on a patient that underwent total knee replacement. The aim of this work is to show that quantitative gait analysis is essential to augment the understanding of the mechanisms underlying gait, thus enabling clinicians to adapt the rehabilitation program to the specific patient. Although the limits of single case reports are obvious, we believe that this evaluation methodology could be beneficial for assessing the effectiveness of rehabilitation programs aimed at achieving an active control of the knee during gait through a correct muscular activation pattern.

Biomechanical Phenomena↗
PubMed1999

Polo-like kinase 1 as a target for human cytomegalovirus pp65 lower matrix protein.

Human cytomegalovirus (HCMV) pp65 protein is the major constituent of viral dense bodies but is dispensable for viral growth in vitro. pp65 copurifies with a S/T kinase activity and has been implicated in phosphorylation of HCMV IE1 immediate-early protein and its escape from major histocompatibility complex 1 presentation. Furthermore, the presence of pp65 correlates with a virion-associated kinase activity. To clarify the role of pp65, yeast two-hybrid system (THS) screening was performed to identify pp65 cellular partners. A total of 18 out of 48 yeast clones harboring cDNAs for putative pp65 binding proteins encoded the Polo-like kinase 1 (Plk1) C-terminal domain. Plk1 behaved as a bona fide pp65 partner in THS control crosses, and the interaction was confirmed by in vitro binding experiments. Endogenous Plk1 was coimmunoprecipitated with pp65 from transiently transfected COS7 cells. In infected fibroblasts, Plk1 was coimmunoprecipitated with pp65 at late infection stages. Furthermore, Plk1 was detected within wild-type HCMV particles but not within the particles of a pp65-negative mutant (RVAd65). The hydrophilic region of pp65 was phosphorylated in vitro by Plk1. These results suggest that one function of pp65 may be to capture a cell kinase, perhaps in order to alter its activity, nucleotide preference, substrate specificity, or subcellular localization to the advantage of HCMV.

Animals↗
PubMed1999

Analysis of function after intra-articular fracture of the os calcis.

Fractures of the os calcis with intra-articular involvement can cause difficulty in treatment and can result in abnormal function throughout the ankle-foot complex. We evaluated the function of the ankle-foot complex and the overall gait pattern after fracture of the os calcis, and we compared the results of surgical and nonsurgical treatment. Those in whom the geometry of the os calcis and joint was restored by reconstructive surgery had better compensation of gait and a better clinical-functional score. Complex disturbances in gait were found in the group of patients that did not undergo open reduction or internal fixation.

Adult↗
PubMed1999

Gait abnormalities in minimally impaired multiple sclerosis patients.

Subclinical evidence of gait abnormalities were identified in a group of seven patients with multiple sclerosis, EDSS scored 0 - 2, without functional limitations. A movement analysis technique was used to identify gait parameters indicative of impaired motor function during walking. Abnormalities related primarily to time-distance parameters (reduced speed of progression, shorter strides, prolonged double support phase) and muscular function (premature recruitment of gastrocnemius and late relaxation of tibialis anterior during stance phase) were identified regardless the severity of the clinical score. The gait analysis procedure was able to provide the clinician with evidence of motor abnormalities prior to functional disturbance observable by a trained physician. These minimal dysfunctions may have resulted from reflex mechanisms impaired by delayed transmission through long loop pathways or else as a result of a nonspecific protective gait strategy to improve balance control. The technique described in this study may be useful to identify earlier starting points for follow-up and physiotherapy.

Adult↗
PubMed1998

Ganciclovir resistance as a result of oral ganciclovir in a heart transplant recipient with multiple human cytomegalovirus strains in blood.

BACKGROUND: The emergence of a ganciclovir (GCV)-resistant human cytomegalovirus (HCMV) strain in a heart transplant recipient (HTR) coinfected by multiple HCMV strains was investigated. METHODS: A HTR with primary HCMV infection was treated with three induction courses of intravenous GCV followed by a 2-month maintenance treatment with oral GCV. HCMV antigenemia, viremia, and leukoDNAemia levels were monitored. GCV susceptibility was analyzed by an immediate-early antigen plaque reduction assay and by a rapid screening assay performed using peripheral blood leukocytes (PBL) as viral inoculum. The viral population in blood was investigated by restriction analysis of multiple genome regions. UL97 and UL54 genes were sequenced in parallel in both HCMV isolates and the relevant PBL samples. A rapid molecular assay for detection and quantitation of the GCV-resistant mutant was developed. RESULTS: The emergence of a GCV-resistant UL97 mutant (Cys-607 --> Tyr) was responsible for treatment failure during oral GCV therapy. The genetic analysis of the HCMV population showed the sequential appearance in blood of two unrelated strains (referred to as A and B). Strain A most likely derived from the transplanted organ and strain B from a subsequent blood transfusion. The resistant variant (Br) emerged from strain B and became predominant "in vivo" under the GCV pressure. However, after foscarnet administration, the resistant mutant disappeared in viral isolates, whereas it was still present as a minor proportion in PBL samples. CONCLUSION: (a) Oral GCV may select resistant strains in transplanted patients; (b) results of the rapid screening assay were clinically useful for shifting to an alternative treatment, thus avoiding the appearance of HCMV disease; (c) virus isolation may not be the most reliable approach to detection of HCMV drug-resistant strains; (d) a novel molecular assay for rapid detection of UL97 Cys-607 --> Tyr mutation directly in clinical specimens was developed, allowing earlier "in vivo" detection of the resistant mutant.

Administration, Oral↗
PubMed1998

Human cytomegalovirus in blood of immunocompetent persons during primary infection: prognostic implications for pregnancy.

Human cytomegalovirus (HCMV) was investigated in peripheral blood leukocytes (PBL) of 52 immunocompetent patients (40 pregnant women) with primary HCMV infection by quantitative determination of pp65 antigenemia, viremia, and leukoDNAemia. pp65 antigenemia was detected in 12 (57.1%) of 21, 4 (25%) of 16, and 0 of 10 patients examined 1, 2, and 3 months after onset, respectively. Viremia was detected in 5 (26.3%) of 19 patients during the first month only. LeukoDNAemia was detected in 20 of 20, 17 (89.5%) of 19, and 9 (47.3%) of 19 patients tested 1, 2, and 3 months after onset, respectively. Four (26.6%) of 15 patients were still DNAemia-positive at 4-6 months, whereas none were positive at >6 months. HCMV was not detected in PBL of 20 HCMV-immune donors or of 9 seropositive subjects with recurrent infection. Virus levels were low by all assays and did not correlate with clinical course of infection, intrauterine transmission, or severity of outcome. Invasive procedures in the presence of maternal leukoDNAemia did not seem to interfere with vertical transmission of HCMV infection.

Adolescent↗
PubMed1998

Functional regions of the human cytomegalovirus protein pUL97 involved in nuclear localization and phosphorylation of ganciclovir and pUL97 itself.

In order to identify functional regions of the human cytomegalovirus protein pUL97 (i) different 5' fragments of the UL97 open reading frame (ORF) were fused to the coding region of the green fluorescent protein and (ii) recombinant vaccinia viruses (rVV) were generated carrying two full-length and 11 mutated UL97 ORFs. The results indicated the presence of an N-terminal region within pUL97 which changed the intracellular distribution of the fusion proteins. pUL97 was localized in the nucleus, but not in the nucleoli, and was detected in the nuclear matrix fraction. Expression of all pUL97 mutants could be confirmed by Western blot analysis. pUL97-associated ganciclovir (GCV) phosphorylation in rVV-infected cells, determined quantitatively by HPLC analysis, was abolished completely using individual UL97 deletion mutants. Phosphorylation of full-length and some of the mutated pUL97 was detected in cells infected with the rVVs. The UL97 constructs carrying point mutations from GCV-resistant HCMV isolates at positions 460M, 520H, 594V, and the 4 aa deletion 590AACR593, also resulted in decreased but not abolished phosphorylation of GCV in the rVV system, whereas the phosphorylation of pUL97 itself was not influenced. The rVV system is a suitable method for quantitatively testing the functional relevance of pUL97 mutations.

Amino Acid Sequence↗
PubMed1998

The Cys607-->Tyr change in the UL97 phosphotransferase confers ganciclovir resistance to two human cytomegalovirus strains recovered from two immunocompromised patients.

Two ganciclovir (GCV)-resistant human cytomegalovirus (HCMV) strains recovered from an AIDS patient (strain VR4990) and a heart transplant recipient (strain VR5474) showed a Cys607-->Tyr change in the UL97-encoded phosphotransferase. No amino acid substitutions were observed in the viral DNA polymerase. Marker transfer experiments showed marked reduction in GCV phosphorylation and drug susceptibility of the recombinant HCMV strain VR4990rec2-1-1. These results further extend the region of the carboxy-terminal domain of the UL97 phosphotransferase involved in GCV substrate recognition.

AIDS-Related Opportunistic Infections↗
PubMed1997

Dissociation between word reading and word copying in a patient with left visual neglect.

A patient with left visual neglect following a right hemisphere infarction is described. When presented with isolated words and nonwords, she made left neglect errors in reading aloud, but not in direct copying. This finding suggests a distinction between two ways of processing orthographic stimuli: depending on the task, the unit of processing can be the letter string or the single letter. In reading, the letter string is treated as a whole while in copying it is processed element-by-element. Left neglect differentially affects the processing of single words: in reading errors involve the left, initial letters, while in copying they involve the single letters, or the left part of the letters, independently of their position within the stimulus.

Aged↗
PubMed1996

Human cytomegalovirus pp65 lower matrix phosphoprotein harbours two transplantable nuclear localization signals.

Human cytomegalovirus phosphoprotein pp65 is targeted to the cell nucleus immediately after infection. Deletion and point mutation analysis of the pp65 gene expressed in insect cells showed that two hydrophilic regions (HP1 and HP2) within the pp65 C-terminal 40% each harboured an independent nuclear localization signal (NLS); strong association to the nuclear stroma also requires the N-terminal domain. Either region, when fused to chloramphenicol acetyltransferase, localized the reporter protein to the nucleus in insect cells as well as in NIH 3T3 cells and human lung fibroblasts. In addition, HP1 was found to be the target of pp65 Ser/Thr phosphorylation in insect cells and a prokaryotically expressed HP1 was actively phosphorylated in vitro by casein kinase II, for which two site clusters map in HP1. These findings indicate that pp65 includes two NLSs, one of which has the potential to be modulated by phosphorylation.

3T3 Cells↗