Histological changes in odontogenic parakeratinized keratocysts treated with marsupialization followed by enucleation.

BACKGROUND: The purpose of this study was to evaluate whether marsupialization treatment induces changes in the histology of odontogenic keratocyst epithelium and to compare our experience with the literature. MATERIAL AND METHODS: A retrospective revision of histological samples was performed. 5 patients with odontogenic keratocyst treated with marsupialization follow by enucleation were selected. Histologic evaluation analyzed the changes in the keratocyst epithelium after marsupialization in terms of type of keratinization, thickness of the epithelium and connective tissue, the presence of acanthosis, the presence and grade of fibrosis, the type and grade of inflammation and the presence and number of mitotic figures and daughter cysts. RESULTS: In our case series, a variation of para-keratinized into ortho-keratinized keratocyst was found in one case, and no significant increases were observed in the epithelium and capsule thickness, or even in the level of inflammation. However, we observed an increase in fibrosis and qualitative changes in inflammation type. CONCLUSIONS: Minor and major histological changes were associated with reduction in cyst volume, which resulted in a simpler and less invasive cystic enucleation after marsupialization.

Salivary biomarkers for diagnosis of systemic diseases and malignant tumors. A systematic review.

BACKGROUND: Saliva evaluation could be a possible alternative to blood and/or tissue analyses, for researching specific molecules associated to the presence of systemic diseases and malignancies. The present systematic review has been designed in order to answer to the question "are there significant associations between specific salivary biomarkers and diagnosis of systemic diseases or malignancies?". MATERIALS AND METHODS: The Preferred Reporting Item for Systematic Reviews and Meta-analysis (PRISMA) statement was used to guide the review. The combinations of "saliva" and "systemic diseases" or "diagnosis" or "biomarkers" or "cancers" or "carcinoma" or "tumors", were used to search Medline, Scopus and Web of Science databases. Endpoint of research has been set at May 2019. Studies were classified into 3 groups according to the type of disease investigated for diagnosis: 1) malignant tumors; 2) neurologic diseases and 3) inflammatory/metabolic/cardiovascular diseases. Assessment of quality has been assigned according to a series of questions proposed by the National Institute of Health. Level of evidence was assessed using the categories proposed in the Oxford Center for Evidence-Based medicine (CEMB) levels for diagnosis (2011). RESULTS: Seventy-nine studies met the inclusion and exclusion criteria. Fifty-one (64%) investigated malignant tumors, 14 (17.5%) neurologic and 14 (18.5%) inflammatory/cardiovascular/metabolic diseases. Among studies investigating malignant tumors, 12 (23.5%) were scored as "good" and 11 of these reported statistically significant associations between salivary molecules and pathology. Two and 5 studies were found to have a good quality, among those evaluating the association between salivary biomarkers and neurologic and inflammatory/metabolic/cardiovascular diseases, respectively. CONCLUSIONS: The present systematic review confirms the existence of some "good" quality evidence to support the role of peculiar salivary biomarkers for diagnosis of systemic diseases (e.g. lung cancer and EGFR).

Absorption and diffusion of a 645 nm diode laser beam in the bone. An ex vivo study.

The present preliminary ex vivo study aims to assess the possible interaction between complex biological systems and laser light, through irradiation of different hard tissue samples. A 645 nm wavelength diode laser was adopted to perform the present evaluation. Due to known similarities to human tissues, swine tissue samples were used. Two samples of cortical bone measuring 4.4 mm and 4.7 mm of thickness and 2 samples of spongeous bone measuring 2.45 mm and 2.9 mm were harvested for the analysis of hard tissues. Mean absorption values were as follows: 128.82 mW standard deviation 8.74 for 2.45 mm spongeous bone sample; 132.34 mW standard deviation 7.66 for 2.9 mm spongeous bone sample; 140.59 mW standard deviation 5.97 for 4.4 mm cortical bone sample and 152.20 mW standard deviation 3.36 for 4.7 mm mucosa and cortical bone sample. Red-light laser with 645nm wavelength has the ability to reach cells in each layer of measured tissues.

Temporal drift in Raman signal intensity during SERS measurements performed on analytes in liquid solutions.

In this communication, we report one factor that could limit the quantitative analysis by SERS, which has not yet been discussed in the literature. Our results show that SERS experiments performed with the substrate immersed in liquid solutions are subjected to a temporal drift in the Raman signal intensity. Measurements were performed using gold nanoparticle suspensions and gold-covered nanostructured ITO surfaces as SERS substrates, immersed in analyte solutions of crystal violet and 4-mercaptobenzoic acid. Depending on the substrate and the conditions used for measurements, the Raman signal can take between 30 min and several hours to stabilize. This effect, if not taken into account, could have a negative impact on the results of the quantitative chemical analysis by SERS performed in situ in liquid solutions.

A wearable, highly stable, strain and bending sensor based on high aspect ratio graphite nanobelts.

A simple and scalable method was developed for the fabrication of wearable strain and bending sensors, based on high aspect ratio (length/thickness ∼10(3)) graphite nanobelt thin films deposited by a modified Langmuir-Blodgett technique onto flexible polymer substrates. The sensing mechanism is based on the changes in contact resistance between individual nanobelts upon substrate deformation. Very high sensor response stability for more than 5000 strain-release cycles and a device power consumption as low as 1 nW were achieved. The device maximum stretchability is limited by the metal electrodes and the polymer substrate; the maximum strain that could be applied to the polymer used in this work was 40%. Bending tests carried out for various radii of curvature demonstrated distinct sensor responses for positive and negative curvatures. The graphite nanobelt thin flexible films were successfully tested for acoustic vibration and heartbeat sensing.

14,15-Dihydroxy-eicosa-5(Z)-enoic acid selectively inhibits 14,15-epoxyeicosatrienoic acid-induced relaxations in bovine coronary arteries.

Cytochrome P-450 epoxygenases metabolize arachidonic acid (AA) to epoxyeicosatrienoic acids (EETs). EETs relax vascular smooth muscle by membrane hyperpolarization. 14,15-Epoxyeicosa-5(Z)-enoic acid (14,15-EE5ZE) antagonizes many vascular actions of EETs. EETs are converted to the corresponding dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH). sEH activity in the bovine arterial endothelium and smooth muscle regulates endogenous EETs. This study examined sEH metabolism of 14,15-EE5ZE to 14,15-dihydroxy-eicosa-5(Z)-enoic acid (14,15-DHE5ZE) and the resultant consequences on EET relaxations of bovine coronary arteries (BCAs). BCAs converted 14,15-EE5ZE to 14,15-DHE5ZE. This conversion was blocked by the sEH inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA). 14,15-EET relaxations (maximal relaxation, 83.4 ± 4.5%) were inhibited by 14,15-DHE5ZE (10 µM; maximal relaxation, 36.1 ± 9.0%; p < 0.001). In sharp contrast with 14,15-EE5ZE, 14,15-DHE5ZE is a 14,15-EET-selective inhibitor and did not inhibit 5,6-, 8,9-, or 11,12-EET relaxations. 14,15-EET and 11,12-EET relaxations were similar in the presence and absence of AUDA (1 µM). 14,15-EE5ZE inhibited 14,15-EET relaxations to a similar extent with and without AUDA pretreatment. However, 14,15-EE5ZE inhibited 11,12-EET relaxations to a greater extent with than without AUDA pretreatment. These observations indicate that sEH converts 14,15-EE5ZE to 14,15-DHE5ZE, and this alteration influences antagonist selectivity against EET-regioisomers. 14,15-DHE5ZE inhibited endothelium-dependent relaxations to AA but not endothelium-independent relaxations to sodium nitroprusside. A series of sEH-resistant ether analogs of 14,15-EE5ZE was developed, and analogs with agonist and antagonist properties were identified. The present study indicates that conversion of 14,15-EE5ZE to 14,15-DHE5ZE produces a 14,15-EET-selective antagonist that will be a useful pharmacological tool to identify EET receptor(s) and EET function in the cardiovascular system.

Patient mortality after graft failure reduces kidney transplant patient survival only in the long term: an "intention to treat" analysis.

The benefits of kidney transplantation over dialysis on patient survival have been demonstrated without considering the outcomes of patients with graft loss. To determine whether mortality after graft failure reduced the transplantation advantage in patient survival, we retrospectively reviewed the outcomes of 918 first-deceased renal transplant recipients from May 1979 to August 2005. Patient survivals were 88% and 72% at 10 and 20 years; cancer (26%) and cardiovascular disease (25%) were the major causes of death. Graft survivals were 72% and 50% at 10 and 20 years; chronic rejection was the major cause of graft loss (50%). Patient outcomes after return to dialysis were reviewed in 224 of 240 patients. The survivals were 97%, 83%, and 70% at 1, 5, and 10 years, respectively; cardio-cerebrovascular disease (56%), infections (9%), cachexia (9%), and cancer (8%) were the major causes of death. Mortality correlated with patient age at transplantation (P< .001). Re-listed patients (96 of 224) were younger (32+/-10 vs 43+/-11 years; P< .001), had a shorter dialysis period pretransplant (3.2+/-3.1 vs 4.3+/-3.9 years; P< .03), and a better survival at 10 years (98% vs 56%; P< .001). Ten-year mortality for patients who returned to dialysis was 20% higher than for patients with a functioning graft (P< .001). The reduction in overall patient survival was 2.2% at 10 years (P=NS), 5% at 15 years (P=NS), and 14% at 20 years (P< .05). The same results have been demonstrated for patients >50 years at transplantation. In conclusion, the mortality rate after return to dialysis did not influence the long-term benefits of kidney transplantation.

Repeated visually-guided saccades improves postural control in patients with vestibular disorders.

One of the most recent and promising theoretical hypotheses for compensation of persistent asymmetry of dynamic vestibulo-ocular gain is sensory substitution. As a switch between oculomotor and vestibulo-ocular systems, saccadic eye movements are engaged in humans to compensate the angular displacement of the head towards the labyrinthine defective side thus preserving the foveal fixation of the target. This study focused on the possibility that saccadic eye movements might also compensate for the impaired vestibulo-spinal reflexes and force the postural system to a more effective control on upright stance and verified whether this sway-stabilizing effect could be applied to patients with vestibular disorders and balance dysfunction. In the first experiment, 27 patients with unilateral labyrinthine hypofunction, 24 patients with central vestibular disorders and 24 healthy volunteers were evaluated by static posturography in 3 different visual conditions: (a) eye open with fixation of a steady target, (b) eye closed, and (c) while performing horizontal visually-guided saccades. The percentage of individuals with a decreased body sway area during the oculomotor task was found to be higher in labyrinthine-defective patients as compared to those with central vestibular disorders and controls. In the second experiment, 46 patients with vestibular disorders both of central and peripheral origin, whose postural control improved by eye-tracking, as assessed by posturography, were later submitted to 12 consecutive training sessions based on repeated visually-guided saccades. Both the saccadic performances and postural control improved in all patients but a more pronounced effect was observed in those with peripheral vestibular disorders. Outcome of this rehabilitation technique was also corroborated by a general reduction of the perceived overall impairment from balance disorders as tested by a specific questionnaire.

[Successful treatment with liposomal doxorubicin and foscarnet in a patient with widespread Kaposi's sarcoma and human herpes virus 8-related, serious hemophagocytic syndrome, after renal transplantation]. / Efficacia del trattamento con doxorubicina liposomiale e foscarnet in un caso di sarcoma di Kaposi disseminato e grave sindrome emofagocitica herpes virus 8 correlate, nel post-trapianto di rene.

BACKGROUND: It is well known that the human herpes virus 8 (HHV8) is linked to several malignancies such as Kaposi's sarcoma (KS). Moreover, pancytopenia due to hemophagocytic syndrome could be associated with HHV8 infection. In renal transplant recipients affected by KS, the tapering of immunosuppression often leads to KS remission, but also results in graft loss in >50% of cases. Chemotherapy and antiviral therapy have also been used, mainly in the presence of visceral involvement. CASE REPORT: We describe a transplant recipient with widespread cutaneous and visceral KS HHV8 associated, complicated by hemophagocytic syndrome. At transplantation the patient's serology for HHV8 was negative, but thereafter it became positive. The first step in treatment (cyclosporine dose reduction until suspension) failed to improve the clinical course. Therefore, therapy combining liposomal doxorubicin and foscarnet was started. Clearance of HHV8 in the blood and complete resolution of the KS lesions were achieved. Immunosuppression with cyclosporine was resumed. No KS relapse has occurred, blood tests for HHV8 are negative, and graft function is good after a 5-yr follow-up. CONCLUSIONS: Therapy combining liposomal doxorubicin and foscarnet was effective in this renal transplant recipient with KS and HHV8 infection and enabled us to resume immunosuppressive therapy; therefore, reducing the risk of acute/chronic rejection.

Salivary biomarkers for diagnosis of systemic diseases and malignant tumors. A systematic review

BACKGROUND: Saliva evaluation could be a possible alternative to blood and/or tissue analyses, for researching specific molecules associated to the presence of systemic diseases and malignancies. The present systematic review has been designed in order to answer to the question "are there significant associations between specific salivary biomarkers and diagnosis of systemic diseases or malignancies?". MATERIALS AND METHODS: The Preferred Reporting Item for Systematic Reviews and Meta-analysis (PRISMA) statement was used to guide the review. The combinations of "saliva" and "systemic diseases" or "diagnosis" or "biomarkers" or "cancers" or "carcinoma" or "tumors", were used to search Medline, Scopus and Web of Science databases. Endpoint of research has been set at May 2019. Studies were classified into 3 groups according to the type of disease investigated for diagnosis: 1) malignant tumors; 2) neurologic diseases and 3) inflammatory/metabolic/cardiovascular diseases. Assessment of quality has been assigned according to a series of questions proposed by the National Institute of Health. Level of evidence was assessed using the categories proposed in the Oxford Center for Evidence-Based medicine (CEMB) levels for diagnosis (2011). RESULTS: Seventy-nine studies met the inclusion and exclusion criteria. Fifty-one (64%) investigated malignant tumors, 14 (17.5%) neurologic and 14 (18.5%) inflammatory/cardiovascular/metabolic diseases. Among studies investigating malignant tumors, 12 (23.5%) were scored as "good" and 11 of these reported statistically significant associations between salivary molecules and pathology. Two and 5 studies were found to have a good quality, among those evaluating the association between salivary biomarkers and neurologic and inflammatory/metabolic/cardiovascular diseases, respectively. CONCLUSIONS: The present systematic review confirms the existence of some "good" quality evidence to support the role of peculiar salivary biomarkers for diagnosis of systemic diseases (e.g. lung cancer and EGFR)

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A prospective randomized trial on azathioprine addition to cyclosporine versus cyclosporine monotherapy at steroid withdrawal, 6 months after renal transplantation.

BACKGROUND: Many attempts have been made to withdraw steroid therapy in renal transplant patients in order to avoid its many side effects. Results have been, so far, controversial. In this randomized prospective study, we compare the efficacy of azathioprine adjuncts to cyclosporine at the time of steroid withdrawal, 6 months after transplantation, versus Cyclosporine monotherapy, in preventing acute rejection. METHODS: One hundred and sixteen kidney transplant patients with good and stable renal function (creatininemia <2 mg/dl) received, in the first 6 months, cyclosporine + steroid. They were then randomized into two groups (A and B), and steroid therapy was withdrawn over 2 months. Group A (58 patients) continued on cyclosporine monotherapy, whereas group B (58 patients) added azathioprine (1 mg/kg/day) at the beginning of randomization and continued on cyclosporine + azathioprine. In both groups, patients resumed steroid therapy at the first episode of acute rejection. Follow-up after randomization was 5.3+/-1.6 years. RESULTS: After 5 years, the incidence of steroid resumption was 57% in group A and 29% in group B (P<0.02); of those, 68% and 88% of them were within 6 months from randomization. Anti-rejection therapy was always successful. Five-year patient and graft survival rates were 90% and 88% in group A and 100% and 91% in group B. Creatininemia did not differ, at follow-up. Side effects differed only for mild and reversible leukopenia caused by azathioprine in group B. CONCLUSION: Cyclosporine plus azathioprine is more effective than cyclosporine monotherapy in reducing the incidence of acute rejection after steroid withdrawal. Graft loss as a result of chronic rejection, mild in both groups, did not differ. Steroid withdrawal is feasible and advantageous, and the addition of azathioprine allowed 71% of our selected patients to remain steroid-free.

Experience with cyclosporine.

Six hundred thirty-eight cadaveric kidney transplant patients between 1983 and 2001 were treated with cyclosporine (CsA) for 87 +/- 58 months. Among 571 patients with follow-up greater than 12 months, the 15-year renal function was investigated to assess the probability of a >30% increase in serum creatinine (sCr) above the month-6 value (baseline) and the impact on graft survival. At 15 years, patient and graft survival rates were 82.7% and 56.1%, respectively, with a 19.5-year half-life (censored for deaths). The main causes of graft loss were chronic rejection (33.0%) and patient death (24%). Cardiovascular disease and neoplasms were the main causes of death. Renal function remained stable in 266 patients (46.6%) with excellent sCr values observed even after a 15-year treatment period. An increased sCr was observed in 305 patients (53.4%) with a 15-year probability of 74%. In 178 patients (59.3%) it was self-limited; their grafts are still functioning well. One hundred three patients (32.8%) lost their graft which was more likely when the sCr had increased >45%. Twenty-four patients (7.9%) died with a functioning graft. Multivariate analysis showed the progression of graft deterioration to be related to proteinuria (P<.0001), a late acute rejection episode (P<.002), or the extent of sCr increase (P<.008). In conclusion, the long-term use of CsA has allowed us to achieve excellent long-term patient and transplant survival rates. Our data indicate a high 15-year probability of an increased sCr, but the rate of progression is slow.

Biofiltration, a new method of short hemodiafiltration: preliminary report.

Four patients previously treated by traditional dialysis (HD, 240 min) were switched to biofiltration (BF, 180-210 min) and followed for twelve months. Before and at the end of this period, clinical and biochemical data were assessed for each patient. Patients treated for 180 min by BF presented no increase in BUN but a significant increase of predialytic phosphorus. The 210 min BF schedule achieved the same pattern of depuration as HD. Acidosis was corrected better in all patients during BF. No hypoxemia and no change of WBC count were observed during BF. Cardiac function, assessed by echocardiography, improved similarly with each session of both methods. BF is a useful alternative treatment procedure for patients with endstage renal failure.

Hemodiafiltration (HD-HF): one year follow-up of nine hours weekly.

Data are presented concerning our experience with hemodiafiltration (HD-HF) in uremic patients. Ten patients previously submitted to regular dialysis treatment, cuprophane membrane (RDT), for the last year twelve hours weekly, were treated for one year, nine hours weekly, HD-HF. Five of ten had suffered discomfort by RDT and five spontaneously chose HD-HF owing to its shorter treatment period. The follow-up of the two treatment schedules did not show any significant difference in absolute and percentage values of small molecules. Hematocrit, body weight and blood arterial pressure were not different following both treatment. Patients submitted to HD-HF complained of no discomfort including patients suffering of dialytic discomfort under RDT. HD-HF has proved as useful and more comfortable than RDT in long-term treatment of patients with chronic renal failure.

The treatment of idiopathic and secondary hydrarthrosis of the knee by intra-articular Rifamycin SV.

Fifty-three patients, 28 females and 25 males, aged from 21 to 68 years, affected with mono- and bilateral intermittent hydrarthrosis of the knee and of a non-inflammatory nature, were included in an open study. All of the knees involved were treated with intra-articular infiltrations with Rifamycin SV. The weekly dosage of Rifamycin SV was 500 mg; the average duration of treatment was 6 weeks. Follow-up 1 year after the end of treatment showed a decrease or regression in joint effusion in all of the knees treated.

Combined effect of vestibular and craniomandibular disorders on postural behaviour.

A correlation has been reported in the dental literature between temporomandibular disorders and musculoskeletal abnormalities, however, the question whether they modify body postural sway remains controversial. In the present investigation, the Craniomandibular Index was used to evaluate the clinical extension of temporomandibular joint dysfunction and related problems in 40 patients with normal vestibular function and in 42 patients with peripheral vestibular disorders. Balance function was assessed by static posturography and body sway area was measured in two conditions: i) eye open, and g) eye closed. Data were compared to those of 40 healthy subjects. Postural control showed a significantly different behaviour between groups with an increase in average body sway in patients with craniomandibular disorders as opposed to controls (p < 0.005). Although the involvement of the stomatognathic apparatus was not quantitatively different in the two groups of patients, those also presenting a peripheral vestibular disorder exhibited greater average body sway than patients with only craniomandibular disorders (p < 0.005). The latter showed a greater average body sway than controls only in the trial with eyes closed (p < 0.05). The results demonstrated that craniomandibular alterations could produce moderate postural instability in patients with a normal vestibular function. Conversely, their association with peripheral vestibular disorders becomes a real challenge to the upright quiet stance probably due to a negative effect of somatosensory origin on the vestibulo-spinal reflex impairment.

[Cancer after kidney transplantation]. / La complicanza neoplastica dopo trapianto di rene.

In our experience, cancer is the second cause of death after renal transplantation. In fact, 27% of the deaths we observed at 15-year follow-up were due to neoplasm and 30% to cardiovascular disease. Cancer is a late complication that becomes more common after the fifth year of transplantation. The probability of suffering from cancer is 8.2% and 29.2% at 5 and 15 year, respectively. More specifically, after a 15-year follow-up, the probability rate for skin cancer is 16.4%, solid cancer 12.8%, lymphoproliferative disease (PTLD) 3% and Kaposi's sarcoma 2.2%, respectively. PTLD has the highest mortality rate (44% after 12 months from diagnosis), followed by solid cancer (24%) and Kaposi's sarcoma (8%). According to the literature, patient-age is the main risk factor for neoplasm; double therapy (Cyclosporine + Azathioprine) can increase both the skin cancer and PTLD risk but not the risk of solid cancer. No difference between Cyclosporine and Tacrolimus has been observed in the incidence of neoplasm. Both in vitro and in vivo studies have documented the ability of Rapamycin to inhibit primary and metastatic tumour growth. If these results are also obtained on patients, Rapamycin will be of considerable interest for the future of immunosuppression. In cancer patients, immunosuppression must always be reduced, especially when dealing with PTLD. After standard chemotherapy, patient mortality rate due to infectious complications is very high. Therefore, chemotherapy should be a second-choice therapy and administered in reduced doses. Many studies have documented that lymphocytes B-cells CD20 positive PTLD can be efficiently treated with Retuximab.