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Biomedical subjects

A Castagna

Publications and source records attributed to A Castagna.

At least 19 recordsLinked to original sources

Transolecranon anterior fracture dislocation.

Between January 1996 and July 2003, 93 consecutive patients operated on with a diagnosis of olecranon fractures were identified from our trauma unit files. Fourteen transolecranon fracture-dislocations were found after a retrospective X-radiographic evaluation. Eight patients were women and six were men, with a mean age of 54 years. There were 4 noncomminuted olecranon fractures, treated with K-wires and single tension-band wiring. The remaining 10 fractures were complex fractures, treated in 3 cases with multiple K-wires and single tension-band wiring, in 2 by use of one-third tubular plates, in 1 with a 3.5-mm dynamic compression plate, and in the remaining 4 with 3.5-mm reconstruction plates. Ligament repair was not performed in any case. Three patients needed reoperation because of early failure of primary fixation. Patients were reviewed at a mean follow-up of 3.6 years. Two reported difficulties in daily activities, none with any symptoms of elbow instability. According to the Broberg and Morrey score, 4 patients had excellent results, 6 had good results, 2 had fair results, and 2 had poor results. Four patients showed signs of degenerative arthritis on the radiographs obtained at follow-up. We conclude that transolecranon fracture-dislocation is an underreported and misdiagnosed injury. Various fixation techniques can restore the anatomic relationships and contour of the trochlear notch; the imperative goal is to obtain a good stable primary fixation and allow early active mobilization.

Adult↗

Measuring, modelling and testing ozone exposure, flux and effects on vegetation in southern European conditions--what does not work? A review from Italy.

Ozone (O3) exposure at Italian background sites exceeds UN/ECE concentration-based critical levels (CLe(c)), if expressed in terms of AOT40. Yet the occurrence of adverse effects of O3 on forests and crops is controversial. Possible reasons include (i) ability of response indicators to provide an unbiased estimate of O3 effects, (ii) setting of current CLe(c) in terms of cut-off value and accumulation level, (iii) response functions adopted to infer a critical level, (iv) environmental limitation to O3 uptake and (v) inherent characteristics of Mediterranean vegetation. In particular, the two latter points suggest that critical levels based on accumulated stomatal flux (CLe(f)) can be a better predictor of O3 risk than CLe(c). While this concept is largely acknowledged, a number of factors may limit its applicability for routine monitoring. This paper reviews levels, uptake and vegetation response to O3 in Italy over recent years to discuss value, uncertainty and feasibility of different approaches to risk assessment.

Crops, Agricultural↗

Key questions in antiretroviral therapy: Italian Consensus Workshop (2005).

A panel of leading Italian specialists in infectious diseases, virologists and immunologists met in Rome in 2005 to review critical data and discuss recommendations for each of the key questions in antiretroviral therapy today: When to start treatment? How to start? When to switch? What to switch to? Whether to stop or not to stop treatment, and how? The method of a nominal group meeting was used and recommendations were graded for their strength and quality using a system based on the one adopted by the Infectious Diseases Society of America. Main conclusions are summarized and critically discussed in this consensus statement, as well as some of the most recent data supporting these recommendations are provided.

Anti-HIV Agents↗

Arthroscopic biceps tendon tenodesis: the anchorage technical note.

Treatment of long head biceps (LHB) tendon pathology has become an area of renewed interest and debate among orthopaedic surgeons in recent years. The background of this manuscript is a description of biceps tenodesis which ensure continual dynamic action of the tendon which depresses the head and impedes lateral translation. A new technique has been developed in order to treat LHB tendon irreversible structural abnormalities associated with cuff rotator lesions. This technique entails the construction of a biological anchor between the LHB and supraspinatus and/or infraspinatus tendons according to arthroscopic findings. The rationale, although not supported by biomechanical studies is to obtain a triple, biomechanical effect. The first of these biomechanical effects which we try to promote through the procedure of transposition is the elimination of the deviation and oblique angle which occurs as the LHB completes its intra-articular course prior to reaching the bicipital groove. Furthermore, we have found this technique extremely useful in the presence of large ruptures of the rotator cuff with muscle retraction. The most common complication associated to this particular method, observed in less than 3%, is failed biological fixation which manifests as subsidence of the tenodesis and consequent descent of the tendon with evident aesthetic deformity.

Arthroscopy↗

Arthroscopic treatment of shoulder ochronotic arthropathy: a case report and review of literature.

Alcaptonuria is an inherited hereditary metabolic disorder, which is associated with various systemic abnormalities and related to the accumulation of homogentisic acid and a derived melanine-like pigment in the connective tissues; the latter is termed ochronosis. We present the arthroscopic findings in the shoulder of a 58-year-old female with ochronotic arthropathy and discuss the role of arthroscopy in the diagnosis and management of this rare metabolic disorder.

Alkaptonuria↗

[Not Available].

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Journal Article↗

Osteoprotegerin and bone turnover markers in heavily pretreated HIV-infected patients.

OBJECTIVES: To characterize osteoprotegerin (OPG) levels, bone remodelling and bone mineral density (BMD) in heavily pretreated HIV-infected patients on antiretroviral therapy, and to evaluate the clinical factors associated with bone density decline. METHODS: Heavily pretreated (> 5 years) HIV-positive patients were enrolled in this cross-sectional, observational study, which was based on a total body bone densitometry examination and a comprehensive evaluation of bone and mineral parameters. RESULTS: Sixty-eight patients (55 male and 13 female) with a median age of 41 years (range 25-60 years) were included in the study. Their antiretroviral treatment lasted for 82 months. On the basis of the World Health Organization criteria, nine patients (13.2%) were osteoporotic [T-score < -2.5 standard deviation (SD)] and 19 patients (27.9%) were osteopenic (T-score between -1 and -2.5). The principal outcomes associated with the presence of a low BMD were high OPG and lysylpyridinoline/creatinine ratio (Dpd) values. Most of the patients (39 of 48; 81.25%) showed vitamin D insufficiency [Vitamin D (25(OH)D) < 18 ng/mL] with secondary hyperparathyroidism (13 of 50 patients: 26%), which proved to be correlated to osteocalcin (BGP) levels [parathyroid hormone (PTH) vs. BGP: r = 0.34; P < 0.01]. There was an inverse correlation between T-scores and serum osteocalcin and alkaline phosphatase (AP) levels, on one hand, and Dpd, on the other. High AP and Dpd values were associated with relative risks of 4.1 [95% confidence interval (CI) = 1.01-17.6] and 7.2 (95% CI = 1.67-31.03), respectively, of a pathological T-score. Multivariate analysis revealed that the factors associated with the presence of osteopenia or osteoporosis were older age and lower body mass index. CONCLUSIONS: About 40% of our heavily pretreated subjects with advanced HIV infection had a low BMD, and 56% (24 of 44 patients) showed a high bone turnover rate with marked osteoclast activation. High OPG levels may protect against bone resorption.

Adult↗

Lopinavir/ritonavir treatment in HIV antiretroviral-experienced patients: evaluation of risk factors for liver enzyme elevation.

OBJECTIVES: To evaluate the risk factors for lopinavir/ritonavir (LPV/r)-related liver enzyme elevation (LEE) in HIV antiretroviral-experienced patients. METHODS: An open prospective observational study was carried out to analyse the incidence and time of LEE development during LPV/r treatment, and to determine whether LEE development was correlated with epidemiological, clinical and biochemical data, immune and virological profiles, concomitant hepatic diseases, antiretroviral therapy, or histological and ultrasonography liver examination results. A diagnosis of LEE was considered when LEE symptoms occurred after LPV/r introduction and was confirmed by a second control within 2 weeks. RESULTS: A total of 782 HIV-positive outpatients have been enrolled in six different Infectious Diseases Departments in Northern Italy since August 2000. Of these patients, 71 (9.1%) developed LEE within 115+/-85 days (mean+/-standard deviation); 13 of these subjects discontinued LPV/r and four were hospitalized. Of the patients with LEE, 74.6% and 25.4% had grade 2 and > or =3 toxicity, respectively. No correlation between LEE and sex, baseline CD4 cell count, viral load, HIV stage, triglyceride values, histological and ultrasonography liver examination results, nevirapine use, or increase in CD4 cell count was observed. Higher baseline alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) values (P < 0.0001 and P=0.004, respectively), younger age (P=0.008), previous hepatitis B virus (HBV) infection (P=0.012), efavirenz use (P=0.04), and hepatitis C virus (HCV) and/or HBV coinfection (P < 0.0001, relative risk 4.78) were significantly related to LEE. No correlations between LEE and the same risk factors as investigated in the whole study population were found in subgroups of patients with HCV and/or HBV infection. CONCLUSIONS: HCV and HBV testing and measurement of baseline ALT values are essential for screening subjects at risk of LEE before starting LPV/r. Strict monitoring of clinical and biochemical parameters should be performed in these patients.

Adult↗

The introduction of the fusion inhibitors in the HAART-regimens.

Interference with HIV entry into target cells provides a novel approach to the treatment of HIV infection. The inhibition of virus fusion with the co-receptor substrate seems the most specific and potentially best way to interfere with HIV infection and replication. The efficacy of the first compound available (enfuvirtide) is evident after the pre-registrative phase II and III studies showing also that the presence of anti gp 41 antibodies in the plasma of the treated patients does not interfere with drug activity. In the failing enfuvirtide treated patients resistant virus was detected in 7/7 after > one year of treatment with genotypic mutations in the HR env domain, however no interclass cross resistance was evidenced. Mutants selected in vivo demonstrated a slight reduction of replication capacity.

Antiretroviral Therapy, Highly Active↗

Resistance and replicative capacity of HIV-1 strains selected in vivo by long-term enfuvirtide treatment.

Enfuvirtide is the prototype member of a new class of anti HIV-1 agents, the fusion inhibitors (FI). In recent clinical trials, the compound has shown its efficacy in combination with other antiretroviral agents in vivo. However mutant strains resistant to the action of the drug arise quite rapidly in vitro and in vivo. To analyze the process of selection and evolution of HIV-1 strains resistant to enfuvirtide in vivo and to evaluate the impact of resistance on viral fitness, 12 HIV-1 infected subjects treated with T20 (enfuvirtide) for at least one year were included in the study. Gp41-coding sequences were amplified from plasma samples of these subjects at baseline and at different time points during treatment. Seven of the 12 subjects showed selection of gp41 mutations under the selective pressure of enfuvirtide. In particular, these mutations clustered in two distinct regions: (i) a mutational hot-spot localized, as previously described, in the first residues of the N-HR domain, with position number 38 as the most heavily mutated, but including also a G36V, a N42D/T, a N43D, a L44M and a L45M; (ii) other mutations were localized further downstream, within N-HR/C-HR junction and in the C-HR. A recombinant assay specifically designed for the determination of HIV-1 phenotype to FI was developed and validated. Using this assay, we observed that all of the 7 mutated clones displayed substantially reduced susceptibility to T20, IC50 ranging from 0.6 to12.8 microg/ml (>100 fold change). The residues whose mutation was associated with a potent reduction in susceptibility were V38, N42, and N43, other positions such as G36, N44 and L45 playing a minor role. None of the mutant HIV isolates showed cross-resistance to T-1249. By the same method, the HIV-1 replicative capacity of the recombinant clones was tested in the absence of drugs, and for each subject, pre-therapy clones were compared to post-therapy ones. In 3/7 subjects a significant decrease in replicative capacity of the recombinant clones was observed. The phenotypic data from this study suggest that the secondary additional mutations, could be associated with improved resistance or recovery of replicative capacity (compensatory mutations).

Amino Acid Sequence↗

In vivo dynamics of the 103N mutation following the withdrawal of non-nucleoside reverse transcriptase inhibitors in HIV-infected patients: preliminary results.

Due to the preferential selection of the fittest HIV mutants, drug-resistant variants are often overgrown by wild-type virus after treatment interruption. Our objective was to investigate the dynamics of the 103N mutation (which usually does not reduce HIV fitness) following the withdrawal of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Patients who were found to have the 103N mutation at or after failure of a NNRTI were selected from an observational database. Two groups of patients were identified: one which continued antiretroviral treatment without NNRTIs (group A) and one which discontinued all anti-retrovirals after failure of an NNRTI (group B). Genotype was obtained by direct sequencing of the replicating plasma virus. Sixty-two subjects tested between July 1998 and December 2002 were included in the analysis, 39 in group A and 23 in group B. At the time of the first resistance test, median (IQR) CD4+ T-lymphocytes and HIV-RNA were 269 (150-449) cells/microL and 25,000 (9,600-83,300) copies/mL. In 31 (50%), 30 (48%), and one case (2%), the 103N mutation was selected by nevirapine, efavirenz, and by delavirdine, respectively. A total of 149 tests were analyzed, with a median (IQR) of 2 (2-3) tests/patient. The median (IQR) interval between failure of NNRTIs and the last resistance test was 11 (5-22) months. Overall, a reversion to wild-type at position 103 was observed in 23/62 (37%) subjects, 14/39 (36%) in group A and 9/23 (39%) in group B. In group A, 14/23 (61%) patients tested within 12 months, 10/16 (63%) of those tested between 12 and 24 months, and 12/14 (86%) of those tested beyond 24 months from NNRTI discontinuation had the 103N mutation. In group B, 14/20 (70%) patients tested within 12 months, 3/4 (75%) of those tested between 12 and 24 months, and none out of two tested beyond 24 months from NNRTI discontinuation had the 103N mutation. In conclusion, following NNRTI discontinuation, in the majority of patients HIV variants carrying the 103N mutation are not overgrown for long by wild-type quasispecies at this position. This suggests that the 103N mutation per se influences minimally the viral fitness in vivo.

Alkynes↗

Early production and scavenging of hydrogen peroxide in the apoplast of sunflower plants exposed to ozone.

The present work set out to define the processes involved in the early O3-induced H2O2 accumulation in sunflower plants exposed to a single pulse of 150 ppb of O3 for 4 h. Hydrogen peroxide accumulation only occurred in the apoplast and this temporally coincided with the fumigation period. The inhibitor experiments suggested that both the plasma membrane-bound NAD(P)H oxidase complex and cell-wall NAD(P)H PODs contributed to H2O2 generation. To investigate the mechanisms responsible for O3-induced H2O2 accumulation further, both production and scavenging of H2O2 were investigated in the extracellular matrix after subcellular fractionation. The results indicated that H2O2 accumulation is a complex and highly regulated event requiring the time-dependent stimulation and down-regulation of differently located enzymes, some of which are involved in H2O2 generation and degradation, not only during the fumigation period but also in the subsequent recovery period in non-polluted air. Owing to the possible interplay between H2O2 and ethylene, the time-course of ethylene emission was analysed too. Ethylene was rapidly emitted following O3 exposure, but it declined to control values as early as after 4 h of exposure. The early contemporaneous detection of increased ethylene and H2O2 levels after 30 min of exposure does not allow a clear temporal relationship between these two signalling molecules to be established.

Cell Membrane↗

Successful treatment of a complicated case of neuroleptic malignant syndrome.

Neuroleptic malignant syndrome (NMS) is a life-threatening reaction often related to neuroleptic drugs, characterized by rigidity, hyperthermia, altered consciousness, and fluctuating blood pressure. We present a case of NMS that followed a doubled oral dose of a drug compound: tranylcypromine sulfate, a monoamine oxidase inhibitor, and trifluoperazine (neuroleptic). The case was complicated by rhabdomyolisis and disseminated intravascular coagulation. It was treated successfully with dantrolene sodium and generous fluid therapy without using neuromuscular blocking agents or dopamine agonists.

Administration, Oral↗

Long-term response in patients receiving HAART including nelfinavir: experience from two Italian centers.

Many studies have demonstrated that the long-term, virological, immunological and clinical effectiveness of highly active antiretroviral therapy (HAART) is mainly related to durable suppression of viral replication. Among the specific antiretroviral agents available today, nelfinavir has been widely used in the last 3 years. This open label, non comparative, retrospective study on 307 patients living with HIV aimed to evaluate the effectiveness of an antiretroviral (ART) regimen including nelfinavir as first-line HAART in terms of rate and durability of viro-immunological response. Most patients, 258/307 (84%), were pre-treated whereas only 49/307 (16%) were treatment naive. The median baseline CD4 cell count was 223 cells/mm3 for naive patients and 317 cells/mm3 for experienced patients whereas median HIV RNA values were 2,500 and 82,000 copies/ml for experienced and naive patients respectively. Median times spent on nelfinavir were 839 and 897 days for experienced and naive patients respectively, with 171/258 pre-treated patients (66%) remaining on nelfinavir-based therapy up to 24 months. Overall, the mean CD4 increase was 196 cells/mm3 with a relevant increment of 165 in experienced patients and 367 cells/mm3 in naive patients (p<0.01). The mean viral load variation in naive patients was -2.22 log10 and in experienced patients -0.53 log10 (p<0.01). In conclusion, nelfinavir, as part of HAART, demonstrated long-term benefit (almost two-thirds of patients stayed on nelfinavir up to 24 months). The response rate in patients naive to antiretroviral therapy was better than for experienced patients. Although there were some differences related to the baseline CD4 level, the overall response rate was good, supporting the role of nelfinavir in HAART.

Adolescent↗

pH-dependent prion protein conformation in classical Creutzfeldt-Jakob disease.

In transmissible spongiform encephalopathies, the cellular prion protein (PrP(C)) undergoes a conformational change from a prevailing alpha-helical structure to a beta-sheet-rich, protease-resistant isoform, termed PrP(Sc). PrP(C) has two characteristics: a high affinity for Cu(2+) and a strong pH-dependent conformation. Lines of evidence indicate that PrP(Sc) conformation is dependent on copper and that acidic conditions facilitate the conversion of PrP(C) --> PrP(Sc). In each species, PrP(Sc) exists in multiple conformations, which are associated with different prion strains. In sporadic Creutzfeldt-Jakob disease (sCJD), different biochemical types of PrP(Sc) have been identified according to the size of the protease-resistant fragments, patterns of glycosylation, and the metal-ion occupancy. Based on the site of cleavage produced by proteinase K, we investigated the conformational stability of PrP(Sc) under acidic, neutral, and basic conditions in 42 sCJD subjects. Our study shows that only one type of sCJD PrP(Sc), associated with the classical form, shows a pH-dependent conformation, whereas two other biochemical PrP(Sc) types, detected in distinct sCJD phenotypes, are unaffected by pH variations. This novel approach demonstrates the presence of three types of PrP(Sc) in sCJD.

Blotting, Western↗

Relation between CD4 cell counts and HIV RNA levels at onset of opportunistic infections.

OBJECTIVE: To evaluate the relation between CD4 and HIV RNA levels at the onset of specific opportunistic infections (OIs) in HIV-infected patients. DESIGN AND METHODS: The OIs occurring between June 1996 and December 1998 were retrospectively reviewed, considering only the episodes of major and minor OIs in patients with simultaneously available CD4 and plasma HIV RNA determinations before clinical onset who had been untreated or on stable antiretroviral therapy (ART) for at least 2 months. RESULTS: Two hundred seventy-four episodes of different OIs were considered in 216 patients; the median CD4 count was 35 cells/mm3 (range: 0-1154 cells/mm(3)), and the median HIV RNA count was 5.1 log cp/mL (range: < 1.9-6.7 log copies/ml). The different HIV RNA levels were significantly associated with different OIs regardless of CD4 and ART (p < .0001), even when only those occurring in patients with a CD4 count of < or = 50 cells/mm(3) were considered (p = .0049). Kaposi sarcoma, esophageal candidiasis, oropharyngeal candidiasis, and Mycobacterium avium complex disease were associated with significantly above-average median HIV RNA levels, and varicella-zoster virus infection was associated with below-average levels. CONCLUSIONS: Different OIs are associated at their onset with significantly different HIV RNA levels, regardless of CD4 cell counts and ART.

AIDS-Related Opportunistic Infections↗

Reversal of CSF positivity for JC virus genome by cidofovir in a patient with systemic lupus erythematosus and progressive multifocal leukoencephalopathy.

We report the case of a 36-year-old woman affected by systemic lupus erythematosus who developed rapidly progressive multifocal leukoencephalopathy. Cidofovir therapy induced disappearance of JC virus genome from the cerebrospinal fluid and stabilization of the MRI picture. Despite the fatal outcome after a few months of disease, cidofovir treatment deserves further testing as single antiviral therapy in HIV-negative PML patients.

Adult↗