Evaluation of Renal Function in Patients Undergoing Lung Transplantation.

BACKGROUND: Acute kidney injury and chronic kidney failure are serious complications after lung transplantation. Glomerular filtration rate (GFR) is the primary indicator of renal function. Several equations have been proposed to evaluate the estimated GFR (eGFR). We compared three different equations to determine which has the better correlation with the development of acute and chronic renal failure in lung recipients. METHODS: Twenty-two patients with a mean age of 54.4 ± 8.5 years underwent lung transplantation from 2010 to 2015. Thirteen (59%) had pulmonary fibrosis, 7 (32%) emphysema, 1 (4.5%) bronchiectasis, and 1 (4.5%) lymphangioleiomyomatosis. In all patients, eGFR was measured preoperatively using Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Levey's Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. In 20 patients (90%) eGFR was calculated at 1, 3, and 6 months. RESULTS: According to CKD-EPI and MDRD, eight patients (36.3%) had preoperative reduction in eGFR, whereas 6 patients (27.2%) had preoperative reduction according to the CG (P = .04). The mean values were higher for the CG (103.2 vs. 102 vs. 94.4). Five patients (22.7%) developed perioperative acute renal failure requesting a dialysis treatment; four of these showed a preoperative eGFR to the highest CG (P = .05). At 1 and 6 months after lung transplantation, the CG, MDRD and CKD-EPI eGFR values were, respectively, 86.6, 84.1 and 76.6 mL/min/1.73m2 and 75.8, 72.7, and 72.3 mL/min/1.73m2. CKD-EPI eGFR values are more predictable than the other equations of AKI. CONCLUSIONS: Preoperative assessment of eGFR using the MDRD and CKD-EPI seems to correlate better than the CG to the prediction of acute renal failure, whereas for the chronic form the three equations seem equivalent.

In vitro evaluation of different antimicrobial combinations against carbapenemase-producing Klebsiella pneumoniae: the activity of the double-carbapenem regimen is related to meropenem MIC value.

Objectives and methods: We evaluated the in vitro activity of different antimicrobial combinations with and without colistin against 39 carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strains (colistin + meropenem/doripenem, colistin + tigecycline, colistin + rifampicin, gentamicin + meropenem, gentamicin + tigecycline and the double-carbapenem regimen meropenem + ertapenem) using the chequerboard method. The triple combination colistin + meropenem + tigecycline was also tested. In addition, killing studies were performed for meropenem + ertapenem. Results: Gentamicin-based combinations showed a high level of synergy. Meropenem + ertapenem was synergic in 12/39 (30.7%) of the strains, whereas based on killing studies 1 × MIC meropenem + 1 × MIC ertapenem and 2 × MIC meropenem + 1 × MIC ertapenem combinations were bactericidal and synergic at 24 h [mean area under the bactericidal curve (AUBC) 54.9 ±âŸ26.1 and 44.2 ±âŸ15.3 compared with 1 × MIC meropenem (134.5 ±âŸ40.1) and 2 × MIC meropenem (126.4 ±âŸ5.4), respectively, P < 0.0001]. When the results were stratified according to meropenem MIC, we found that the degree of synergy significantly increased for isolates with lower meropenem (and not ertapenem) MICs, up to an MIC of 128 mg/L. Among colistin-containing combinations, synergy was observed in 18/39 (46.1%), 33/34 (97%), 24/39 (61.5%) and 17/39 (43.5%) of the strains for colistin + meropenem, colistin + rifampicin, colistin + tigecycline and colistin + doripenem, respectively, including colistin-resistant strains. Colistin + meropenem + tigecycline at subinhibitory concentrations resulted in the absence of growth of 37/39 strains (94.8%). Conclusions: Our in vitro data suggest that colistin might be a valid therapeutic option against CR-Kp, even in the presence of colistin resistance, whereas the double-carbapenem regimen represents a viable option when colistin is not recommended, especially if the meropenem MIC is ≤ 128 mg/L. Since traditional antimicrobial susceptibility reports are not sufficiently informative for clinicians, synergy testing as well as actual meropenem MIC evaluation should always be performed in the case of CR-Kp infections.

Bactericidal and synergistic activity of double-carbapenem regimen for infections caused by carbapenemase-producing Klebsiella pneumoniae.

Available therapeutic options against carbapenem-resistant Klebsiella pneumoniae (CR-Kp) are limited because of the high level of resistance to other antimicrobial classes including polymyxins. The double-carbapenem regimen has been recently considered a possible therapeutic strategy. In the present study, we evaluated the in vitro bactericidal and synergistic activity of a double-carbapenem regimen consisting of ertapenem plus high-dose meropenem in a series of patients with healthcare-associated CR-Kp infections in whom the use of colistin was not indicated because of potential nephrotoxicity and/or resistance. In vitro synergy was evaluated using checkerboard and killing studies. A total of 15 patients were included in the study, with sepsis, severe sepsis and septic shock found in two (13.3%), five (33.3%) and one (6.7%) patients, respectively. Overall, the clinical/microbiological response was 12/15 (80%). Synergy was observed in 11/14 (78.6%) isolates using the checkerboard method whereas in killing studies 12/14 (85.7%) and 14/14 (100%) strains were synergistic and bactericidal at 24 h at concentrations of 1 × MIC MEM+1 × MIC ERT and 2 × MEM+1 × MIC ERT, respectively, with a significant decrease of log CFU/mL compared with other combinations (p <0.0001). The double-carbapenem regimen showed clinical and in vitro effectiveness in patients with CR-Kp infections.

Ten years' experience with a pyrocarbon prosthesis replacing the proximal interphalangeal joint. A prospective clinical and radiographic follow-up.

We prospectively assessed the subjective, objective, and radiographic results at 1, 2, and 5 years in 65 patients who had pyrocarbon proximal interphalangeal prostheses inserted between 2001 and 2010. Further operations were done on 10 of the 89 joints (four for prosthetic extraction and arthrodesis, two for component changes, and four for soft tissue procedures). At 1 year, the visual analogue scale score for pain at rest had improved to 0 cm from a pre-operative 4 cm, pain at activity from 6 to 1.8 cm, and Disability of the Arm, Shoulder and Hand score from 40 to 25. Range of movement and grip strength were unchanged. At 5 years, 31 joints (21 patients) had a complete radiographic follow-up. Seven proximal and 12 distal components showing zones of osteolysis at 1 year had stabilized and were inert or integrated at 5 years. Three proximal and three distal components had osteolytic zones at 5 years. Forty-seven of 59 patients were pain-free at rest at 1 year, and 19 of 21 at 5 years. No late revisions or loosening occurred.

Hemi-hamate osteochondral transplantation in proximal interphalangeal dorsal fracture dislocations: a minimum 4 year follow-up in eight patients.

Fracture dislocations of the PIP joint are challenging to treat. In hemi-hamate arthroplasty, the palmar lip joint surface is reconstructed using an osteochondral graft from the hamate and the immediate stability permits early movement. In the long term, collapse of non-vascularized osteochondral grafts might lead to degenerative arthritis. We examined the radiographic result after a minimum of 4 years with special reference to the development of osteoarthritis and its relation to clinical symptoms in eight patients, mean age 49 (25-66) years. After a mean of 60 (48-69) months, the arc of motion was 67° (45°-95°) at the PIP joint and grip strength was 91% of the uninjured side. The visual analogue score for pain (0-100) was 10 (0-70) mm. Severe arthritis (grade IV) was found in two and mild arthritis (grade II) in another two patients, but only one of these four cases had troublesome pain. The hemi-hamate technique is an attractive alternative to other treatment options, but some cases develop osteoarthritis in the medium term.

Nitrous oxide discretely up-regulates nNOS and p53 in neonatal rat brain.

AIM: Animal studies suggest that neuronal cell death often results from anesthetic administration during synaptogenesis. Volatile anesthetics are strongly involved in triggering neuronal apoptosis, whereas other inhalational agents (xenon) demonstrate protective effects. Nitrous oxide (N2O) has modest pro-apoptotic effects on its own and potent, synergistic toxic effects when combined with volatile agents. Recent findings suggest that, during periods of rapid brain development, the enhanced neurodegeneration triggered by anesthetic drugs may be caused by a compensatory increase in intracellular free calcium, a potent activator of neuronal nitric oxide synthase (nNOS). Anesthesia-induced neuro-apoptosis is also activated via the intrinsic and the extrinsic apoptotic pathways because both pathways involve p53, a key regulatory gene. The molecular events related to neuronal cell apoptosis are not completely understood. To gain further insight into the events underlying neuro-apoptosis, we analyzed the transcriptional consequences of N2O exposure on nNOS, iNOS and p53 mRNA levels. METHODS: The study used 2 groups of postnatal day seven Sprague/Dawley rats (N=6 each) that were exposed for 120 minutes to air (75% N2, 25% O2) or N2O (75% N2O, 25% O2; this N2O concentration is commonly used to induce anesthesia and has been demonstrated to trigger neurodegeneration in postnatal day seven rats). Total RNA was isolated from each brain and expression analyses on iNOS and nNOS transcripts were performed using relative Real-Time C-reactive protein PCR (using G3PDH as a housekeeping gene). A semi-quantitative RT-PCR analysis was performed on the p53 transcript (using Ciclophylin A as a housekeeping gene). RESULTS: Statistical analysis (REST 2005) revealed a significant, 11-fold up-regulation (P=0.026) of the nNOS transcript but no significant changes in iNOS transcription. The p53 mRNA was up-regulated almost 2-fold (P=0.0002; Student's t-Test; GraphPad Prism 4.00) in N2O-treated samples relative to room-air samples. CONCLUSION: Our preliminary data show that N2O induced a selective increase in nNOS and p53 transcription. These new findings provide evidence of pro-apoptotic action by N2O and may shed new insight on its toxic effects; however, further investigations are necessary.

Mechanisms of protection by pantoprazole against NSAID-induced gastric mucosal damage.

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) can be associated with severe adverse digestive effects. In clinical settings, proton pump inhibitors have proven to be effective in preventing and healing NSAID-induced gastroduodenal lesions. The present study investigates the mechanisms of protection afforded by pantoprazole against gastric injury induced by different NSAIDs in rats. Animals were orally treated with indomethacin (100 micromol/kg), diclofenac (60 micromol/kg), piroxicam (150 micromol/kg) or ketoprofen (150 micromol/kg). Thirty minutes before NSAIDs, animals received pantoprazole 6 or 60 micromol/kg orally. Four hours after NSAIDs, the following parameters were assessed: histomorphometric evaluation of gastric mucosal damage; gastric mucosal levels of myeloperoxidase (MPO), malondialdehyde (MDA), reduced glutathione as an index of non-proteic sulfhydryl compounds (GSH), and prostaglandin E2 (PGE2); mucosal cyclooxygenase-1 and -2 (COX-1, COX-2) mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). Separate experiments were carried out to assay the effects of pantoprazole on gastric acid secretion in pylorus-ligated rats. The in vitro influence of pantoprazole (1-10 microM) on the oxidation of low density lipoproteins (LDLs) induced by copper sulphate was also examined. All NSAIDs elicited mucosal necrotic lesions associated with neutrophil infiltration and reduction of PGE2 levels. Increments of MPO and MDA contents, as well as a decrease in GSH levels, were detected in the gastric mucosa of indomethacin-, piroxicam- or ketoprofen-treated animals. Indomethacin enhanced mucosal COX-2 expression, while not affecting COX-1. At the oral dose of 6 micromol/kg pantoprazole did not affect NSAID-induced mucosal damage, whereas at 60 micromol/kg it markedly reduced injuries provoked by all test NSAIDs. Pantoprazole 60 micromol/kg also reversed the effects of NSAIDs on MPO, MDA, and GSH mucosal contents, without interfering with the decrease in PGE2 levels or indomethacin-induced COX-2 expression. However, at both doses, pantoprazole inhibited acid secretion in pylorus-ligated rats. Furthermore, pantoprazole concentration dependently reduced the in vitro oxidation of LDLs. Our results suggest that besides inhibiting acid secretion, the protection afforded by pantoprazole against NSAID-induced gastric damage depends on a reduction in mucosal oxidative injury, which may also account for an increment of sulfhydryl radical mucosal bioavailability. It is also suggested that pantoprazole does not influence the down-regulation of gastric prostaglandin production associated with NSAID treatment.

[Highly malignant papillary cystadenocarcinoma of the tongue: a case report]. / Su un caso di cistoadenocarcinoma papillare della lingua ad alto grado di malignità.

Papillary cystadenocarcinoma (PC) of the tongue is an extremely rare malignant neoplasm arising from the minor salivary glands. Its anatomopathological features are sufficiently characterized although clinical manifestation and biological behavior are not yet well defined. The Authors describe a highly malignant case of PC of the tongue in a 71-year-old man treated with surgery, followed by radiotherapy. Clinical and anatomopathological characteristics of this rare neoplasm are described. A review of the international literature confirms how unusual this disorder is and explains the poor tumor histotype characterization. Finally the Authors assert that this is the first case of highly malignant PC with localization limited to the tongue reported in literature. The Authors conclude suggesting a clinical-therapeutic procedure to deal with this rare pathology.

The "lazy S-shaped" plication of the SMAS-platysma musculoaponeurotic system: a 10-year review.

Morphological changes that appear with the aging process are expressed by loss of the youthful face and neck contours. A "lazy S-shaped" plication involving the superficial musculoaponeurotic system (SMAS)-Platysma has been performed to recover the face and neck contour. On the neck, the posterior segment of the lateral portion of the muscle was stretched upward and backward to the mastoid. On the face, plication was done laterally and superiorly to the corner of the mouth toward the zygomatic arch. The anterior platysmal bands were approached in the midline to reinforce the muscle sling of the neck. Extensive skin dissection with suction lipectomy under direct visualization of the submental and cervical fat were associated. Photographs were taken preoperatively, 1 year, and 10 years after the surgery. Face and neck contour at 10 years was compared with that at 1 year after the surgery and with the patient look before the surgery. Improvement of the face and neck contour was achieved in all patients at 1 year postoperatively. At 10 years after the surgery the face and neck contour was equal or eventually better than before the surgery.

[Effects of one cycle of inhalation crenotherapy with radioactive fluoridated oligomineral]. / Studio oggettivo degli effetti di un ciclo di crenoterapia inalatoria con acque oligominerali radioattive fluorurate delle Terme di Merano.

The objective of the study was to test the effects of inhalation crenotherapy using the radioactive, fluoridated oligomineral waters from the Merano Spa on both subjects with specific upper respiratory tract phlogosis and normal subjects. The double-blind study was performed on a population of 27 adults of both sexes treated with radioactive-fluoridated water (group A) and 20 subjects, suffering from the same chronic catarrh pathology, selected with the same criteria but treated with inhalation of steam and an aerosol using drinking water from the municipal water supply (group C). In addition, a group of 13 subjects--which in terms of age and sex were statistically comparable to groups A and C but who did not show any signs of acute or chronic upper respiratory tract pathologies (group B) were also treated with the radioactive-fluoridated waters. All subjects included in the study underwent the following tests before and after the cycle of crenotherapy: Objective E.N.T. examination. Computerized Active Anterior Rhinomanometry. Detection of the ciliary mucous transport (CMT) time. Nasal cytology. Physical and immunochemical examination of the nasal mucous. The results of this study--seen in the trend in some parameters monitored both before and after the cycle of crenotherapy using Merano Spa water--clearly show that that the crenotherapy studied had an effect on aspecific chronic phlogosis of the upper respiratory tract. In fact, among other things, group A showed decreased nasal resistance, increased nasal respiratory flow, normalized mucociliary transport, decreased bacterial flora and an increased number of plasma cells in the rhinocytogram. In addition there was an increase in the following values in the nasal mucous: Albumin, non-secretory Immunoglobulin and the secretory portion of secretory Immunoglobulin A. None of these variations are seen in the results from the control group treated with municipal drinking water. After treatment with Merano spa water, the pathology-free subjects showed variations in the parameters in line with those found for group A. This biological reality can most likely be attributed to the favorable response of the respiratory mucosa, promoting anti-infection defenses.

H-Shaped, double-contour plication in abdominoplasty.

H-shaped, double-contour plication, by reducing the longitudinal and transverse abdominal diameters, improves the waistline and reinforces the entire anterior abdominal wall, with better accommodation of the cutaneous flap. The decrease in the longitudinal diameter allows lowering and fixation of the cutaneous flap without tension.

cis requirements for the efficient production of recombinant DNA vectors based on autonomous parvoviruses.

The replication of viral genomes and the production of recombinant viral vectors from infectious molecular clones of parvoviruses MVMp and H1 were greatly improved by the introduction of a consensus NS-1 nick site at the junction between the left-hand viral terminus and the plasmid DNA. Progressive deletions of up to 1600 bp in the region encoding the structural genes as well as insertions of foreign DNA in replacement of those sequences did not appreciably affect the replication ability of the recombinant H1 virus genomes. In contrast, the incorporation of these genomes into recombinant particles appeared to depend on in cis-provided structural gene sequences. Indeed, the production of H1 viral vectors by cotransfection of recombinant clones and helper plasmids providing the structural proteins (VPs) in trans, drastically decreased when more than 800 bp was removed from the VP transcription unit. Furthermore, titers of viral vectors, in which most of the VP-coding region was replaced by an equivalent-length sequence consisting of reporter cDNA and stuffer DNA, were reduced more than 50 times in comparison with recombinant vectors in which stuffer DNA was not substituted for the residual VP sequence. In addition, viral vector production was restricted by the overall size of the genome, with a mere 6% increase in DNA length leading to an approximately 10 times lower encapsidation yield. Under conditions fulfilling the above-mentioned requirements for efficient packaging, titers of virus vectors from improved recombinant molecular DNA clones amounted to 5 x 10(7) infectious units per milliliter of crude extract. These titers should allow the assessment of the therapeutic effect of recombinant parvoviruses expressing small transgenes in laboratory animals.

Controlled conformational transitions in the MVM virion expose the VP1 N-terminus and viral genome without particle disassembly.

Antisera were raised against peptides corresponding to the N-termini of capsid proteins VP1 and VP2 from the parvovirus minute virus of mice. Epitopes in the 142-amino-acid VP1-specific region were not accessible in the great majority of newly released viral particles, and sera directed against them failed to neutralize virus directly or deplete stocks of infectious virions. However, brief exposure to temperatures of 45 degreesC or more induced a conformational transition in a population of full virions, but not in empty viral particles, in which VP1-specific sequences became externally accessible. In contrast, the VP2 N-terminus was antibody-accessible in all full, but not empty, particles without prior treatment. An electrophoretic mobility shift assay, in which particles were heat-treated and/or preincubated with antibodies prior to electrophoresis, confirmed this pattern of epitope accessibility, showing that the heat-induced conformational transition produces a retarded form of virion that can be supershifted by incubation with VP1-specific sera. The proportion of virions undergoing transition increased with temperature, but at all temperatures up to 70 degreesC viral particles retained structure-specific antigenic determinants and remained essentially intact, without shedding individual polypeptide species or subunits. However, despite the apparent integrity of its protective coat, the genome became accessible to externally applied enzymes in an increasing proportion of virions through this temperature range, suggesting that the conformational transitions that expose VP1 likely also allow access to the genome. Heating particles to 80 degreesC or above finally induced disassembly to polypeptide monomers.

Late spontaneous extrusion of a texturized silicone gel mammary implant.

A case report of late spontaneous extrusion of a 250-cm(3), round, texturized silicone gel mammary implant, 14 months after implantation, is presented. The irregular surface of the implant, the location of the implant pocket, and the absence of the fibrous capsule were responsible for alterations in the skin thickness. In addition, the pressure exerted by the implant against the skin provides for stasis with venous thrombosis at the inferior portion of the breast. The continuous manipulation of the breast over a thin skin with vascular alterations led to the skin perforation with implant extrusion.

[Effects of sulphur-arsenic-ferrous water treatment on specific chronic phloglosis of the upper respiratory tract]. / Studio sperimentale degli effetti di un ciclo di trattamento con acque solfato-arsenicali-ferruginose su flogosi croniche aspecifiche delle vie aeree superiori.

The aim of the present study was to demonstrate the therapeutic effect sulphurous-arsenical-ferruginous waters from had on aspecific phlogosis of the upper respiratory tract (URT). This double-blind study involved treating 37 adults of both sexes with sulphurous-arsenical-ferrignous water (group A) and another 14 subjects, again suffering from the same aspecific, chronic catarrhal disorder and selected with the same criteria, with the aerosol vapor inhalation of drinking water from the city mains (group B). All subjects included in the study underwent the following tests both before and after the cycle of crenotherapy: Objective E.N.T. examination Anterior Active Computerized Rhinomanometry (AACR) Mucociliary transport time (MTT) Nasal cytology Physical and immunochemical examination of the nasal mucous. The post crenotherapy variations achieved indicate that the sulphurous-ferruginous waters have a beneficial therapeutic effect: indeed, the mucosa was able to perform its complex functions, particularly specific and aspecific defense of the organism. In fact, among other things, group A showed decreased resistance and increased nasal respiratory flow, normalized of mucociliary transport, decreased bacterial layer and increased plasma cells in the rhinocytogram, and an increase in albumin, non secretory immunoglobulin and the secretory portion of secretory immunoglobulin A in the nasal mucosa. None of these variations--many of which were statistically significant--were seen in the controls group treated with drinking water from the public mains.

Extramucosal rhinoplasty with videoscopic assistance.

Extramucosal approach provides for earlier results, less edema and echymoses. The final inspection using the magnificence of the videoscopic camera makes visible small irregularities at the cut edge of the nasal bones, upper portion of the lateral cartilage, and dorsal aspect of the septal cartilage. The removal of both cartilaginous and bony spicules provides improvements in the quality of the results. Videoscopic assistance in association with extramucosal approach is very helpful to achieve an aesthetic and functional result in rhinoplasty.

The NS2 polypeptide of parvovirus MVM is required for capsid assembly in murine cells.

Mutants of minute virus of mice (MVM) which express truncated forms of the NS2 polypeptide are known to exhibit a host range defect, replicating productively in transformed human cells but not in cells from their normal murine host. To explore this deficiency we generated viruses with translation termination codons at various positions in the second exon of NS2. In human cells these mutants were viable, but showed a late defect in progeny virion release which put them at a selective disadvantage compared to the wildtype. In murine cells, however, duplex viral DNA amplification was reduced to 5% of wildtype levels and single-strand DNA synthesis was undetectable. These deficiencies could not be attributed to a failure to initiate infection or to a generalized defect in viral gene expression, since the viral replicator protein NS1 was expressed to normal or elevated levels early in infection. In contrast, truncated NS2 gene products failed to accumulate, so that each mutant exhibited a similar NS2-null phenotype. Expression of the capsid polypeptides VP1 and VP2 and their subsequent assembly into intact particles were examined in detail. Synchronized infected cell populations labeled under pulse-chase conditions were analyzed by differential immunoprecipitation of native or denatured extracts using antibodies which discriminated between intact particles and isolated polypeptide chains. These analyses showed that at early times in infection, capsid protein synthesis and stability were normal, but particle assembly was impaired. Unassembled VP proteins were retained in the cell for several hours, but as the unprocessed material accumulated, capsid protein synthesis progressively diminished, so that at later times relatively few VP molecules were synthesized. Thus in NS2-null infections of mouse cells there is a major primary defect in the folding or assembly processes required for effective capsid production.

[Treatment of chronic inflammation of the upper respiratory airways by inhalation thermal therapy with sulfur-sulfate-bicarbonate- carbonate-alkaline earth mineral water: a study of nasal cytology]. / Trattamento delle flogosi croniche delle vie aeree superiori con crenoterapia inalatoria solfureo-solfato-bicarbonato-carbonica-alcalinoterrosa: studio della citologia nasale.

The purpose of the paper is to better characterise changes occurred in nose cytology in a group of 50 subjects affected by chronic inflammation of upper respiratory airway. The patients were random shared in two groups: group A 40 subjects treated using sulphurous thermal water and a group B (control), 10 cases, treated using placebo saline solution. The post-therapy evaluation of nasal cytology showed an improvement of the chronic inflammation in 65% of group A patients (diminution of bacterial dust 65%, diminution of PMN cells in 60% of cases and disappearance of metaplasy notes in all the cases of group A. No statistical modifications were observed in control group. Moreover were observed a increase of plasma-cell number much more in group A. The author conclusion is that a period of thermal therapy using sulphur-sulphate-alkaline-earth metals water in chronic inflammation of the nose, throw pharmacological and physical actions, cause an improvement of the chronic inflammation and a normalisation of nose cytology.