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Biomedical subjects

C U Casciani

Publications and source records attributed to C U Casciani.

At least 19 recordsLinked to original sources

Reconstruction of the nasal dorsum with autologous rib cartilage.

The authors present their experience with the correction of deformities of the nasal saddleback using rib cartilage grafts. They present a review of international literature on this topic, analyzing 33 patients selected from 452 cases of rhinoplasties performed between January 1990 and December 2004 at the Department of Plastic and Reconstructive Surgery of the University of Rome "Tor Vergata." Nasal saddleback is one of the most complicated defects to correct surgically. It can be a consequence of nasoethmoid-orbital fractures and is in this case associated with other evident signs like telecanthus, teleorbitism, or orbital dystopia. It can be also a consequence of surgical procedures in the nasal area where a loss of bone or septal cartilaginous support has occurred. They compare the techniques employed in the reconstruction and describe the advantage of the use of cartilage from the 11th rib and evaluate the results of an engineering analysis of tension forces on the rib cartilage. Of the total number of patients treated, good cosmetic results were obtained in 84% of the cases and excellent functional results in almost all of the cases (94%).

Adult↗

Characterization of a novel HLA-Cw*02 variant, Cw*0208, in a Caucasian individual.

We describe an additional HLA-Cw*02 variant, HLA-Cw*0208, which has been identified in a renal transplant recipient of Caucasian origin (Italy). After performing preliminary serological typing, we analyzed exons 2 and 3 of the HLA-C locus polymorphism by cloning the amplified DNA and using a sequence-based typing method. The new allele differs from Cw*020202 by one nucleotide substitution at nucleotide 61 (G-->A) of exon 2, which translates to a difference of one amino acid at residue 21 (His-->Arg) of the HLA-C heavy chain. We propose that Cw*0208 was generated by a random point mutation in codon 21 from the Cw*020202 allele, or through gene conversion of Cw*020202 with another allele, probably the Cw*1205 and Cw*1602 alleles.

Alleles↗

Hemodiafiltration with post-dilution reinfusion of the regenerated ultrafiltrate: a new on-line technique.

AIMS: All convective hemodiafiltration techniques require a replacement fluid, which must have an adequate electrolytic composition and must be sterile and pyrogen-free. Using an integrated adsorption cartridge, the ultrafiltrate can be "regenerated" and used as a replacement fluid (hemo-filtrate reinfusion; HFR). The aim of this study was to evaluate whether the HFR technique as suggested in its original configuration could be improved by inverting the purification sequence (post-dilution HFR; PDHFR) in order to increase the purification efficiency of the whole system. METHODS: We performed standard HFR in 6 uremic patients during 6 months and, subsequently, during further 6 months, PDHFR. The dialytic efficacy of the two techniques and the filter blood loss were evaluated. Moreover, we studied how both techniques affected cytokine levels. RESULTS: We observed a significant increase of urea extraction and of Kt/V values in PDHFR. An equally significant improvement was observed in regard to the extraction of beta2-m and the blood loss. Furthermore, IL6 and TNFalpha decreased significantly after PDHFR treatment. CONCLUSIONS: HFR has proven to be an easy-to-perform hemodiafiltration technique, capable of resolving the typical problem of the other hemodiafiltration technique, the availability and production of a sterile and ultrapure reinfusion solution. The inversion of its configuration has allowed us to improve three aspects that have characterized, in our experience, the treatments performed in the original geometry: the removal of both urea and beta2-m, and the filter. Finally, it's notable that the decrease in cytokines levels achieved with PDHFR might attenuate the uremic micro-inflammatory state.

Adult↗

Prospective randomized trial of submucosal hemorrhoidectomy with radiofrequency bistoury vs. conventional Parks' operation.

BACKGROUND: Postoperative pain has always been the main adverse effect of the surgical treatment for hemorrhoids. Surgical techniques evolved mainly to solve this problem as well as postoperative bleeding, stenosis and recurrence. This randomized study compared the results obtained using submucosal hemorrhoidectomy with radiofrequency bistoury with those of the conventional Parks' operation. METHODS: A total of 102 patients were randomized to undergo submucosal hemorrhoidectomy with radiofrequency bistoury (51 patients) or conventional Parks' haemorrhoidectomy (51 patients); loss of some patients at follow-up resulted in 49 and 45 patients available for analysis, respectively. The operating time, amount of pain (VAS scale, 1-10), postoperative analgesic requirement, intra- and postoperative complications, length of hospital stay and patient satisfaction were documented. RESULTS: In comparison to Parks' technique, use of radiofrequency bistoury reduced mean operating time (61.2 min vs. 37.4 min; p<0.05), first postoperative day pain score (5.9 vs. 4.0; p<0.05), pain score at first evacuation (5.7 vs. 4.2; p>0.05), postoperative stay (2.2 days vs. 1.3 days; p<0.05), and pain score on postoperative day 7 (3.6 vs. 2.8; p>0.05). Fecal incontinence was never observed. Incontinence to flatus with spontaneous resolution within 2-3 weeks was reported by 4 subjects in each surgical group. Urinary retention requiring catheterization occurred in 21 subjects in the radiofrequency bistoury group and in 18 patients in the control group. No complications nor recurrences were reported at the 6-month follow-up in either group. CONCLUSIONS: Performing submucosal hemorrhoidectomy with radiofrequency bistoury improves the results obtained with Parks' technique, allowing us to simplify the surgical procedure, reduce operating time, postoperative pain and bleeding, and shorten the hospital stay.

Adult↗

Living donor transplant: wider selection criteria.

The availability of cadaveric donor organs is insufficient for actual needs. The organ demand increases by 20% per year. Living donor transplant (LDT) may be a valid therapeutical alternative provided one uses proper criteria. LDT provides many advantages, like improved patient and organ survival, short waiting time, and the possibility to carefully plan the procedure. Potential risks include perioperative mortality and renal dysfunction in the kidney donor. At present, kidney LDTs in Italy represent 8% of the total, with an organ survival rate of 97% after 1 year (vs 93% for cadaveric transplants) and donors mortality rate of almost null. Most LDTs are performed from kinsmen. Presently, law no. 458, 26 June 1967, is in force in Italy for kidney LDT and law no. 453, 16 December 1999, for liver LDT. The foundations of LDT are, of course, the recipient's condition, the donor's motivation, and the altruism of the donation. It is desirable that in the future an increasing number of LDT be performed, supported by a careful, widespread health education regarding organ donation from living subjects and by the possibility to obtain insurance for the donor, which has been considered but never provided by actual laws.

Animals↗

Sirolimus in kidney transplantation from marginal donors.

Nephrotoxicity caused by calcineurin inhibitors can lead to either delayed graft function or long-term decline of renal function after kidney transplantation. Therefore, recipients of renal transplants from marginal donors require non-nephrotoxic immunosuppression. Eighteen patients received kidney transplants from marginal donors, with a calcineurin inhibitor-free immunosuppressive regimen, based on basiliximab, mycophenolate mofetil, steroids, and sirolimus. Renal graft biopsy was performed in all cases before surgery. Mean follow-up was 11.8 months. We report immediate renal function in 9 patients, delayed graft function in 5 and acute tubular necrosis in 4 patients. One patient was successfully treated for biopsy-proven acute rejection. Hypercholesterolemia and hypertriglyceridemia were the most common adverse effects (n = 13) associated with arthralgia (n = 2) and thrombocytopenia (n = 2). Five patients underwent a switch to tacrolimus, due to sirolimus-induced side effects. Immunosuppression without the use of calcineurin inhibitors is a safe and effective regimen in kidney transplantation, although sirolimus-related side effects still represent a morbidity factor in these patients.

Biopsy↗

Marginal donors in liver transplantation.

Marginal liver donor criteria included the following: obesity (weight >100 Kg or BMI >27), age >50 years; macrovesicular steatosis >50%; intensive care unit stay >4 days; prolonged hypotensive episodes of >1 hour, and <60 mm Hg with high inotropic drug use (dopamine, [DPM] > 14 microg/kg per minute); cold ischemia time >14 hours, peak serum sodium >155 mEq/L; sepsis, viral infections, and alcoholism; high levels of bilirubin, ALT, and AST, or extrahepatic neoplasia. Between August 1992 and May 2003, we performed 251 liver transplants in 241 patients of whom 155 are presently alive. We used 124 (49.4%) standard donors and 127 (50.6%) marginal donors. Among the group that received a standard donor, 81 (65.3%) are still alive. Among recipients of organs from marginal donors. 81 (63.8%) are still alive. We also assessed the quality of donors according to the severity of recipient disease. For standard donors these outcomes were 61.5% for UNOS 1, 37.5% for UNOS 2A, 73.2% for UNOS 2B, and 80% for UNOS 3 for marginal donors they were 46.1% for UNOS 1, 53.6% for UNOS 2A, 70.7% for UNOS 2B, and 63.6% for UNOS 3. Among the patients who received a liver from a donor >60 years old, there were no survivors in UNOS 1 and 2A, but there were good results in groups 2B and 3. These results suggest there is no difference between marginal and standard donors, even in sick patients, with the exception of donor age.

Age Factors↗

Polyoma virus BK and renal dysfunction in a transplanted population.

INTRODUCTION: Reactivation of polyoma virus BK (BKV) is increasingly recognized as a cause of severe renal-allograft dysfunction. The aim of the present study was to evaluate prevalence of BKV infection and activity in a population of kidney (KT) and liver (LT) transplant patients and search for a possible correlation with renal dysfunction. METHODS: We studied 118 patients for BKV viruria and, when present, for BKV viremia. We also assessed HCV status. RESULTS: Among 16 patients with BKV viruria (5 LT and 11 KT), eight showed BKV viremia (one LT and seven KT). Among BKV viruria-positive patients, three LT recipients were HCV-positive. All LT BKV viruria-positive patients showed normal renal function with a mean serum creatinine (sCr) blood level of 0.9 mg% and a mean blood urea nitrogen (BUN) value of about 36 mg%. The mean transplant age was 2.5 years. In contrast, KT BKV viruria-positive patients showed impaired renal function which was slightly worse in patients who also displayed BKV viremia, namely, a mean sCr blood level 1.7 mg% and a mean BUN value about 80 mg%. The mean transplant age was 7 years. CONCLUSION: Based on these findings, it seems that BKV viruria in renal allograft recipients may be associated with viremia and related to nephropathy that may lead to allograft rejection. The study will be completed with a 2-year follow-up of positive patients to assess the possible relationship between BKV active infection and eventual decrease of renal function and loss of transplanted organ.

Adult↗

Plasmaperfusion on triptophan columns can improve the clinical outcome of patients affected with myasthenia gravis.

UNLABELLED: Myasthenia Gravis (MG) is a neuromuscular disease often associated with thymic pathology due to neuromuscular transmission impairment by circulating antibodies directed against the cholinergic postsynaptic receptor on the neuromuscular junction (Anti-AchR-Ab). The treatment of MG includes cholinesterase inhibitors, steroids and thymectomy. Plasmapheresis can remove Anti-AchR-Ab but more recently plasma-perfusion (PP), a more specific apheresis for selective removal of noxious plasma components, has been developed. AIM OF THE STUDY: To study the effect of PP treatment, performed by using specific immunocolumns for Anti-AchR-Ab, on the clinical outcome of MG patients non-responder to steroid therapy or thymectomy. MATERIALS AND METHODS: We treated 8 patients suffering from severe MG by a cycle of 6 sessions of PP. We used columns containing triptophan as a specific ligand for Anti-AchR-Ab. In order to evaluate the effectiveness of treatment we used functional tests (muscular tests, respiratory function, electromyography) and laboratory tests (Anti-AchR-Ab; immunoglobulins, complement fractions, immunocomplexes). RESULTS: After one to three PP sessions, early clinical improvement in bulbar and respiratory symptoms were found in all patients and EMG showed improvement of neuromuscular transmission. Serum concentration of immunological markers decreased progressively and significantly during the treatment. Clinical improvements were progressive despite the tendency for Anti-AchR-Ab to reach initial values between one session and another. We observed no side effects due to the type of immunocolumns used. CONCLUSIONS: Triptophan columns appear to be able to remove large quantities of Anti-AchR-Ab and immunological markers from plasma. Our experience shows that PP performed using triptophan columns in patients suffering from severe MG provides good clinical results, improving patients' outcome, without any risk linked to the procedure.

Acetylcholine↗

Artificial organs and transplantation.

Nowadays artificial devices are not able to totally and undefinitely replace the loss of function of all vital organs and artificial organs can be used only to bridge the time to transplantation, which must be considered the first choice in the therapeutical approach for many chronic diseases. Since general population aging process is leading to an increase of organ demand, the gap between performed and requested transplantation is hard to fill. Xenotransplantation is nowadays only an experimental alternative solution and we have to do our best using available artificial organs to increase and improve the survival of patients waiting for transplantation. In this meeting we particularly dealt about organ function replacing therapy, especially regarding the kidney, heart, liver, pancreas and ear.

Animals↗

[Milligan-Morgan hemorrhoidectomy with a radiofrequency scalpel].

BACKGROUND: Postoperative pain has always been the main adverse effect of surgical treatment for hemorrhoids. Therefore, surgical techniques evolved mainly to solve this problem and, secondly, postoperative bleeding, recurrences and stenosis. METHODS: Two homogeneous groups of 20 patients each were investigated. Both of them were affected by fourth grade hemorrhoidal prolapse and were homogeneous for age, sex and presentation symptoms. Patients previously treated for other proctologic diseases were excluded. A group was treated with standard Milligan-Morgan hemorrhoidectomy and the other with radiofrequency scissors. Every patient underwent a follow-up protocol based on outpatient visits at 15, 30, 45 postoperative days and 3, 6 and 12 months. RESULTS: The results show a substantial similarity between these techniques. However, radiofrequency scissors further improved the simplicity of the technique and the postoperative adverse effects. In particular, the procedure lasted 7 minutes less with radiofrequency scissors. Patients treated with the radiofrequency technique had their first postoperative evacuation 24 hours before the standard technique and reduced the mean postoperative hospital stay at 2.5 days (4.5 days in the standard group). The incidence of postoperative pain was reduced in patients treated with radiofrequency scalpel and the follow-up controls in both groups didn't show any complication as stenosis or incontinence. CONCLUSIONS: The radiofrequency-performed Milligan-Morgan hemorrhoidectomy is a valuable technique that improves the classical difficulties in execution, reducing the length of hospital stay and the incidence of postoperative pain or other complications.

Adult↗

[Description of a case of giant adrenal myelolipoma and survey of the literature].

Adrenal myelolipoma is a benign tumor affecting the adrenal gland. It is composed by adipose cells and myelopoietic cells present in each normal differentiating stage of the bone marrow. The neoplasia is often asymptomatic, sometimes leading to very large adrenal masses (more than 10 cm in diameter). These are often called "giant myelolipoma". A case is reported and a survey of the literature on this topic is made; the present knowledge of this disease as well as its diagnosis and treatment are discussed also.

Adrenal Cortex Neoplasms↗

Identification of the novel allele B*4427 and a confirmatory sequence (B*44022).

This report presents a novel allele, HLA-B*4427, which was identified in a bone marrow donor of Caucasian origin, and a confirmatory sequence (B*44022). Sequence analysis revealed the new allele differs from B*44021 by a single nucleotide exchange at position 668 (C-->T), which is located in exon 4. At the protein level, it is the only B*44 variant to produce an Ala in place of a Val at codon 199. Its structure suggests that it may have originated from a point mutation in B*44021 or by gene conversion with a variety of HLA-B alleles. Cloning and sequencing of the allele B*44022 revealed a sequence identical to B*44021 and B*44 exon 4, with the codon GTC (Val) in position 199.

Alleles↗

CD44 ligation on peripheral blood polymorphonuclear cells induces interleukin-6 production.

Polymorphonuclear cells (PMNs) contribute to the initiation and progression of the immune response by mediating cytotoxicity, phagocytosis, and cytokine secretion. Because CD44 serves as a cytotoxic-triggering molecule on PMNs, it was hypothesized that it could also trigger cytokine production. In this study, the effect of anti-CD44 antibodies on interleukin-6 (IL-6) production in human PMNs was assessed. By using a reverse transcriptase-polymerase chain reaction, it was shown that PMNs stimulated with a mouse monoclonal or a rabbit polyclonal F(ab)(2) anti-CD44 transcribe IL-6 messenger RNA. A similar effect was obtained when an anti-CD44 antibody was replaced with hyaluronic acid (HA). Kinetic studies showed that anti-CD44 and HA induced IL-6 gene transcription, initiated 3 hours after stimulation, peaked between 12 and 24 hours, and disappeared after 48 hours. Analogous results were achieved when secreted IL-6 protein was measured by enzyme-linked immunosorbent assay in the PMN culture supernatants. To characterize which metabolic pathways regulated CD44-dependent IL-6 production in PMNs, an RNA polymerase inhibitor, actinomycin D, and 2 protein kinase inhibitors, such as genistein and staurosporine, were tested. Actinomycin D and genistein blocked IL-6 production, whereas staurosporine did not, suggesting that CD44-dependent IL-6 production requires gene transcription and tyrosine kinase activity. Furthermore, the relationship between CD44 and cytokines that affect PMN function, including interferon gamma (IFNgamma) and IL-2, was investigated. Without CD44 cross-linking, IFNgamma did not trigger IL-6 production. However, on CD44 cross-linking, IFNgamma produced a strong synergistic effect on IL-6 syntheses in human PMNs. (Blood. 2001;97:3621-3627)

Animals↗

Protective role of tauroursodeoxycholate during harvesting and cold storage of human liver: a pilot study in transplant recipients.

BACKGROUND: Ischemia-reperfusion injury is a major cause of early graft dysfunction after liver transplantation. Tauroursodeoxycholic acid (TUDCA), a natural amidated hydrophilic bile salt, protects from cholestasis and hepatocellular damage in a variety of experimental models, as well as from ischemia-reperfusion injury. We investigated in the human liver transplantation setting the effect of the addition of TUDCA at time of liver harvesting and cold storage on the intra- and postoperative enzyme release and liver histopathology at the end of cold storage, at reperfusion, and 7 days after transplantation. METHODS: Eighteen patients undergoing elective liver transplantation were studied, including 6 serving as controls. In six patients, TUDCA was added to the University of Wisconsin solution used during harvesting and cold storage, to reach final concentrations of 2 mM. In three of these patients, TUDCA (3 g) was infused in the portal vein of the donor before organ explantation; in the other three cases, TUDCA was given through both routes. RESULTS: The use of TUDCA did not cause adverse events. The release of aspartate aminotransferase in the inferior vena cava blood during liver flushing was significantly lower (P=0.05) in TUDCA-treated than in control grafts, as were cytolytic enzyme levels in peripheral blood during the first postoperative week (P<0.02). At electron microscopy, an overt endothelial damage (cytoplasmic vacuolization, cell leakage, and destruction with exposure of hepatocytes to the sinusoidal lumen) was invariably found in control grafts, both at reperfusion and at day 7 after transplant. These features were significantly ameliorated by TUDCA (P<0.001). Several ultrastructural cytoplasmic abnormalities of hepatocytes were seen. Among these, damage to mitochondria matrix and crystae was significantly reduced in TUDCA-treated versus control grafts (P<0.01). Mild to severe damage of bile canaliculi was a constant feature in control biopsies, with dilatation of canalicular lumen and loss of microvilli. Both these abnormalities were markedly ameliorated (P<0.001 by TUDCA). The best preservation was observed when TUDCA was given through both routes. CONCLUSIONS: The use of TUDCA during harvesting and cold storage of human liver is associated with significant protection from ischemia-reperfusion injury. The clinical significance of this findings must be studied.

Adenosine↗

Impact of donor-specific antibodies on chronic rejection occurrence and graft loss in renal transplantation: posttransplant analysis using flow cytometric techniques.

BACKGROUND: Improvements in immunosuppressive therapy have greatly reduced acute rejection (ARj) episodes, ensuring better short-term graft outcome, but have not modified long-term survival in renal transplantation. It is now well accepted that chronic rejection (CRj) can be determined by both immune and/or nonimmune mechanisms. The aim of this study was to evaluate the importance of the posttransplant humoral immune response towards mismatched HLA graft antigens in CRj occurrence and graft outcome. METHODS: Serum samples from 120 nonpresensitized renal transplant recipients were prospectively screened for 1 year after surgery by means of flow cytometry cross-match (FCXM) and FlowPRA beads (microbeads coated with purified HLA class I and class II antigens) assays. All transplants were followed-up for 2 years or until graft removal. RESULTS: FCXM monitoring identified donor-specific antibodies (DS-Abs) in 29 (24.2%) of 120 transplanted patients. Correlation with clinical data highlighted a higher incidence of ARj in DS-Abs-positive patients compared to negative patients (62% vs. 13%, P<0.00001). Furthermore, graft failure occurred more frequently among FCXM-positive patients than among negative patients (34% vs. 1%, P<0.00001). The deleterious effect of DS-Abs on graft function was confirmed by serum creatinine levels 2 years after transplantation. These were in fact higher in subjects producing DS-Abs than in subjects with only ARj (mean creatinine: 2.5+/-1.3 mg/dL vs.1.7+/-0.5 mg/dL, P=0.04). FlowPRA analysis of DS-Ab HLA specificity highlighted the presence of anti-HLA class I antibodies in 85% of FCXM-positive patients, who also presented with a higher incidence of HLA-B mismatches than FCXM-negative patients (1.23+/-0.66 vs. 0.92+/-0.59, P=0.02). CONCLUSIONS: Flow cytometric techniques are precious tools for investigating the activation of the humoral response against HLA antigens of the graft in renal transplantation. DS-Abs production has a worse impact on organ function and survival than ARj episodes. These findings represent further proof of the threat posed by DS-Abs on long-term graft function and draw attention to the need for a specific immunosuppressive therapy aimed at counteracting the different kinds of immune activation toward graft.

Adult↗

Vitamin E suppresses 5-lipoxygenase-mediated oxidative stress in peripheral blood mononuclear cells of hemodialysis patients regardless of administration route.

A number of pathological conditions caused by oxidative stress have been reported in uremic patients undergoing maintenance hemodialysis (HD). Enhanced lipid peroxidation was previously observed in peripheral blood mononuclear cells (PBMCs) of HD patients. Upregulation of 5-lipoxygenase (5-Lox) activity and protein content with enhanced production of leukotriene B(4) (LTB(4)) and membrane lipoperoxides was also shown in PBMCs of HD patients. Administration of free vitamin E specifically inhibited 5-Lox activity without affecting gene expression at the protein level. To assess whether oral or intramuscular (IM) administration of vitamin E may suppress 5-Lox in HD patients, PBMCs from 16 subjects on maintenance HD therapy for at least 6 months were investigated before and after a short course of IM or oral administration of vitamin E (8 patients per group). PBMCs from 13 healthy controls were also evaluated and assumed as the reference standard. Vitamin E significantly reduced lipid peroxidation, LTB(4) content, and 5-Lox activity in PBMCs, whereas 5-Lox gene expression at the protein level was not affected. There were no significant differences in these parameters between patients treated with IM or oral vitamin E. PBMCs of HD patients showed enhanced membrane lipid peroxidation and release of LTB(4), both linked to upregulation of 5-LOX: 5-Lox activity and related oxidative stress were significantly (although not completely) suppressed by vitamin E regardless of the administration route.

Administration, Oral↗