Search PubMed⌕ Search

Biomedical subjects

F Rinaldi

Publications and source records attributed to F Rinaldi.

At least 19 recordsLinked to original sources

Polyclonal and monoclonal antibodies for treating acute rejection episodes in kidney transplant recipients.

BACKGROUND: Registry data shows that between 15-35% kidney recipients will undergo treatment for at least one episode of acute rejection within the first post transplant year. Treatment options include pulsed steroid therapy, the use of an antibody preparation, the alteration of background immunosuppression, or combinations of these options. In 2002, in the US, 61.4% patients with an acute rejection episode received steroids, 20.4% received an antibody preparation and 18.2% received both. OBJECTIVES: To determine the benefits and harms of mono- or polyclonal antibodies (Ab) used to treat acute rejection in kidney transplant recipients. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (in The Cochrane Library, issue 2, 2005), MEDLINE (1966-June 2005), EMBASE (1980-June 2005), and the specialised register of the Cochrane Renal Group (June 2005). SELECTION CRITERIA: Randomised controlled trials (RCTs) in all languages comparing all mono- and polyclonal antibody preparations, given in combination with any other immunosuppressive agents, for the treatment of acute graft rejection, when compared to any other treatment for acute rejection. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for eligibility and quality, and extracted data. Results are expressed as relative risk (RR) with 95% confidence intervals (CI). MAIN RESULTS: Twenty one trials (49 reports, 1387 patients) were identified. Trials were generally small, incompletely reported, especially for potential harms, and did not define outcome measures adequately. Fourteen trials (965 patients) compared therapies for first rejection episodes. Ab was better than steroid in reversing rejection (RR 0.57, 95% CI 0.38 to 0.87) and preventing graft loss (death censored RR 0.74, CI 0.58 to 0.95) but there was no difference in preventing subsequent rejection or death at one year. Seven trials (422 patients) investigated Ab treatment of steroid-resistant rejection. There was no benefit of muromonab-CD3 over ATG or ALG in either reversing rejection, preventing subsequent rejection, preventing graft loss or death. AUTHORS' CONCLUSIONS: In reversing first rejection, any antibody is better than steroid and also prevents graft loss, but subsequent rejection and patient survival are not significantly different. In reversing steroid-resistant rejection the effects of different antibodies are also not significantly different. Given the clinical problem caused by acute rejection, data are very sparse, and clinically important differences in outcomes between widely used interventions have not been excluded. Standardised reproducible outcome criteria are needed.

Acute Disease↗

Co-solubilization of poorly soluble drugs by micellization and complexation.

The use of combined approach of surfactants and cyclodextrins in solubilization of poorly soluble drugs has been described in literature. In this report, a mathematical model has been developed to provide the quantitative basis for this approach. First, by way of hypothetical examples and simulations, the influence of various interaction parameters on the phase solubility profile is presented. Additionally, the model results are compared with (a) results reported by Yang et al., with NSC-639829, sodium lauryl sulfate (SLS) and sulfobutyl-ether-beta-cyclodextrin ((SBE)(7M)-beta-CD) and (b) solubility of methylprednisolone, a model poorly soluble drug, in the presence of its water-soluble 'surfactant-like' prodrug, methylprednisolone 21-hemisuccinate, and (SBE)(7M)-beta-CD. The model shows good agreement with experimental data. Furthermore, theoretical simulations show that the combined solubility is less than the sum of the individual solubility values in cyclodextrins and surfactants. Based on the hypothetical case and the two examples, the factors affecting the phase solubility profile in mixed solutions of surfactants and cyclodextrins are presented. Finally, the limitations of the model to explain co-solubilization by surfactants and cyclodextrins are discussed.

Chemistry, Pharmaceutical↗

Effect of hydroxypropyl cellulose (HPC) on dissolution rate of hydrochlorothiazide tablets.

Hydrochlorothiazide (HCTZ) 60 mg strength tablets containing commonly used excipients and hydroxypropyl cellulose, marketed as either Klucel-EF (HPC, NF from Hercules, USA) or HPC-L (HPC, NF from Nippon Soda, Japan), as a binder were manufactured using identical aqueous wet granulation process. The tablets containing Klucel-EF as a binder exhibited higher dissolution rates than those manufactured using HPC-L. The granulations containing Klucel-EF or HPC-L showed no significant differences in compressibility and compactibility based on analysis performed using the Instron-Stress-Strain Analyzer. Both HPC grades met NF specifications and there were no differences for the NF test results in the certificates of analysis by their respective vendors. Further evaluation of both HPC grades indicated that the cloud point values for Klucel-EF and HPC-L in water were 39(+/- 1) and 48 degrees C, respectively. The differences in cloud points of Klucel-EF and HPC-L were correlated to the differences in the percent hydroxypropoxy content and the degree of molecular substitution, which were higher for Klucel-EF than for HPC-L. These structural features make Klucel-EF less hydrophilic. Since the cloud point of Klucel-EF was similar to the dissolution medium temperature of 37(+/- 2) degrees C, it may present a less viscous layer surrounding the HCTZ granules enabling faster dissolution of the drug.

Cellulose↗

Tethered cord syndrome.

AIM: Tethered cord syndrome (TCS) is a stretch-induced disorder of the spinal cord. Tethering is due to an inelastic structure anchoring the caudal end of the spinal cord as a short and thick filum terminale. Spinal dysraphism is occasionally associated,but the etiological relationship between these disorders remain unclear. Other anomalies may be concurrently found as hydromielia and Arnold-Chiari malformation. METHODS: The authors analysed neuroradiological findings in 5 children and 9 patients of 20-24 years of age; there were four male and ten female. The criteria for inclusion were neurological disturbances (disorders!) localizable to the level of the conus and evidence for spinal dysraphism. The purpose of this study was to make the precise diagnosis and make also precise planning for therapy, conservative or surgical treatment. RESULTS: The age of diagnosis of TCS varies from under 1 year to 14 years and is very rarely as late as adulthood. TCS can present late and insidiously with progressive gait disturbances, atrophy of various muscle groups or the entire limb, loss of reflexes,loss of sensation in the sacral dermatomes, sphincter disturbances, gait abnormality and pain in the gluteal, perianal and other pelvic areas. The diagnosis involves standard X-RAY examination, CT and CT-Mielography but MRI is now a diagnostic method of choice. Surgical untethering of the cord is recommended. The associated pain responds best to surgical treatment; ambulation and bladder function may improve as well. CONCLUSIONS: However sphincter dysfunction often remains a permanent problem. Given the potential for rapid deterioration with incomplete neurological recovery, even prophilactic surgery seems advisable. The patient need to be followed up, if not operated upon.

Adult↗

Health-related quality of life and sleep disorders in Parkinson's disease.

Parkinson's disease (PD) is a chronic, progressive, disabling movement disorder with a clear impact on Health-Related Quality of Life (HRQoL). We investigated the correlations between HRQoL and sleep disorders measured with the Parkinson's disease Sleep Scale (PDSS) and the motor and non-motor aspects of the disease. A correlation was found between HRQoL and the scores from PDSS, motor and depression scales. We conclude that more attention should be paid to the non-motor aspects of PD to attempt to improve HRQoL.

Aged↗

Diurnal variation in spontaneous eye-blink rate.

The daily pattern of spontaneous eye-blink rate (BR), a non-invasive peripheral measure of central dopamine activity, was investigated in 24 healthy subjects. The spontaneous eye-blink rate showed a stable pattern in morning, midday and afternoon hours. A significant increase was found at the evening time point (20.30 h). The finding is suggestive of a late evening increase of central dopamine activity. An increased level of subjective sleepiness was also found at the same evening point, at a time corresponding to the 'evening wake maintenance zone' or the 'forbidden zone for sleep'. A possible hypothesis is that the 'forbidden zone for sleep' may reflect a dopamine-mediated activation that counteracts a rising sleep drive. The role of diurnal variation of dopamine function should be considered both in the choice of the drug treatment regimen, and in the evaluation of biological and neuropsychological parameters.

Adolescent↗

Clonality analysis suggests that early-onset acute lymphoblastic leukaemia is of single-cell origin and implies no major role for germ cell mutations in parents.

Childhood leukaemia presenting at a young age has been suspected of resulting from a leukaemogenic mutation in parental germ cells, either spontaneously or due to the exposure of a parent to leukaemogenic environmental hazards, particularly ionizing radiation. Mathematical modelling of leukaemogenesis suggests that any such patient would be especially prone to multiple independent leukaemogenic events leading to multiclonality in terms of cell of origin (analogous to bilaterality in familial retinoblastoma). To test this hypothesis we have carried out a search for multiclonal leukaemogenesis in infant and childhood acute lymphoblastic leukaemia (ALL). We used a polymerase chain reaction-based analysis of the X-linked monoamine oxidase A (MAOA) gene locus to study the clonality of marrow samples obtained from female paediatric ALL patients at the time of disease presentation. We obtained presentation samples from 102 patients of whom 72 were found to be informative at the MAOA locus. These included 20 infant leukaemias (< 1 year at diagnosis). Sixty-six samples were found to be unequivocally monoclonal while the remaining six could not, with certainty, be assigned a clonal origin. We also obtained bone marrow aspirates at first relapse as well as at presentation from eight patients. In each case the same pattern of X-linked allelic inactivation was observed at both time points of the course of the disease. No evidence was found for leukaemic multiclonality in any age group at presentation or for leukaemic 'clone-switching' in relapse. These findings suggest that both infant and childhood ALL is of single-cell origin and implies that leukaemic predisposition resulting from germ cell mutation is unlikely to have a major role in their pathogenesis.

Adolescent↗

Delta-opiate DPDPE in magnetically oriented phospholipid micelles: binding and arrangement of aromatic pharmacophores.

D-Penicillamine(2,5)-enkephalin (DPDPE) is a potent opioid peptide that exhibits a high selectivity for the delta-opiate receptors. This zwitterionic peptide has been shown, by pulsed-field gradient 1H NMR diffusion studies, to have significant affinity for a zwitterionic phospholipid bilayer. The bilayer lipid is in the form of micelles composed of dihexanoylphosphatidylcholine (DHPC) and dimyristoylphosphatidylcholine (DMPC) mixtures, where the DMPC forms the bilayer structure. At high lipid concentration (25% w/w) these micelles orient in the magnetic field of an NMR spectrometer. The resulting 1H-13C dipolar couplings and chemical shift changes in the natural abundance 13C resonances for the Tyr and Phe aromatic rings were used to characterize the orientations in the bilayer micelles of these two key pharmacophores.

Biophysical Phenomena↗

[Use of ropivacaine in axillary brachial plexus block].

The aim of the study was to evaluate the efficiency and safety of ropivacaine, in comparison with bupivacaine, in axillary brachial plexus block. 24 patients, undergoing upper limb surgery, was divided into 2 homogeneous groups and the local anaesthetics was administered: A (ropivacaine 0.75%, 25 ml; total dose 187.5 mg) and B (bupivacaine 0.5%, 25 ml; total dose 125 mg). The axillary plexus block was executed with the help of an electrostimulator. The results show that using ropivacaine the onset-time is lower and the duration of sensory and motor block is higher than using bupivacaine. In conclusion we can affirm that ropivacaine is a new step in local anaesthetic field.

Adult↗

[Peridural analgesic therapy in orthopedic surgery: comparison of ropivacaine and bupivacaine].

The aim of our study was to compare the efficiency of ropivacaine and bupivacaine, in epidural administration, in postoperative analgesia. 20 patients, undergone knee surgery, in epidural anaesthesia (bupivacaine 0.5%-2 mg/Kg-1 administered in level L3L4), was divided into 2 groups (10 each one) and the local anaesthetics in study was administered by epidural catheter with an elastomeric pump: A (ropivacaine 0.15%) and B (bupivacaine 0.15%). The results demonstrate that ropivacaine is better than bupivacaine to keep a check on analgesia in postoperative pain.

Adult↗

[Use of mivacurium in orthopedic surgery: comparison of 2 different-dose inductions].

The aim of our study was to evaluate the efficiency and safety of mivacurium, comparing two dose-induction in patients undergone a minor orthopaedic surgery. 30 patients were divided into two groups and mivacurium were administered at the dose of 0.15 mg Kg-1 and 0.20 mg Kg-1 respectively. The results confirmed its efficiency in short surgery. Mioresolution was excellent only in the second group (0.20 mg Kg-1) despite an histamine-related blood pressure reduction.

Adjuvants, Anesthesia↗

Steroid-growth factor interaction in human prostate cancer. 1. Short-term effects of transforming growth factors on growth of human prostate cancer cells.

In order to better define potential mechanisms of growth regulation in human prostate cancer cells, we have compared biological responses (such as short-term response to both transforming growth factor alpha and beta; TFG alpha and TFG beta) in relation to hormone sensitivity of LNCaP, DU145, and PC3 cells. Androgen receptor (AR) and epidermal growth factor receptor (EGF-R) content of each cell line was also investigated. In addition, expression of EGF, TGF alpha, and TGF beta was evaluated through immunofluorescent staining. Growth of androgen non-responsive PC3 cells was stimulated by TGF alpha (about 35%) and inhibited by TGF beta (more than 50%), with respect to controls, after 48 h exposure. Conversely, AR-positive, hormone-responsive LNCaP cells proved to be poorly sensitive, at least short-term, to either growth factor. Furthermore, high levels of both EGF-R and TGF alpha, and a fairly high amount of EGF, were found in DU145 cells and, to a lesser extent, in LNCaP cells; in contrast, PC3 cells exhibited low expression levels of both receptors (EGF-R) and ligands (EGF, TGF alpha), but displayed remarkable TGF beta binding and relatively high levels of endogenous TGF beta. Overall, these results suggest a differential sensitivity to TGF alpha and TGF beta by prostate cancer cells; TGF alpha response seems not to be proportional to the EGF-R content of individual cell lines.

Androgens↗