The impact of early surgical treatment of tracheal stenosis on neurorehabilitation outcome in patients with severe acquired brain injury.

INTRODUCTION: Acquired tracheal stenosis (TS) is a potentially life-threatening condition following prolonged intubation and/or tracheostomy in adult patients with severe Acquired Brain Injury (sABI), requiring a tracheal resection and reconstruction. METHODS: We included 38 sABI adult patients with TS, admitted at a post-acute Neurorehabilitation Hospital. Disability Rating Scale (DRS) and other functional assessment measures were recorded at admission (t1), before TS surgical treatment (t2), and at discharge (t3). Patients were defined as 'improved' when they changed from a more severe to a less severe disability, between time t2 and time t3, and as "not improved" when they did not show any further improvement between t2 and t3, or they already exhibited a disability improvement since time interval t1-t2. RESULTS: Time interval between the injury onset and TS surgical treatment (t2-t0) was associated with the patient's disability improvement, suggesting the t2-t0 time interval ≤ 115 days as a cutoff value for a possible functional recovery. A t2-t0 time interval ≤ 170 days is also associated to absence of persistent dysphagia. CONCLUSIONS: Early TS surgical treatment within 115 days from the injury onset contributes to the improvement of the disability level in patients with sABI, optimizing their functional outcomes and recovery potential.

Circulating androgen receptor combined with 18F-fluorocholine PET/CT metabolic activity and outcome to androgen receptor signalling-directed therapies in castration-resistant prostate cancer.

The association between choline uptake and androgen receptor (AR) expression is suggested by the upregulation of choline kinase-alpha in prostate cancer. Recently, detection of AR aberration in cell-free DNA as well as early 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) were associated with outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone and enzalutamide. We aimed to make a direct comparison between circulating AR copy number (CN) and choline uptake at FCH-PET/CT. We analysed 80 mCRPC patients progressing after docetaxel treated with abiraterone (n = 47) or enzalutamide (n = 33). We analysed AR CN from plasma samples using digital PCR and Taqman CN assays and total lesion activity (TLA) and metabolic tumor volume (MTV) on FCH-PET/CT at baseline. A meaningful correlation was showed among AR gain and TLA/MTV compared to AR non-gained cases (P = 0.001 and P = 0.004, respectively), independently from type of treatment. Multivariate analysis revealed that AR CN and only TLA were associated with both shorter PFS (P < 0.0009 and P = 0.026, respectively) and OS (P < 0.031 and P = 0.039, respectively). AR gain appeared significantly correlated with choline uptake represented mainly by TLA. Further prospective studies are warranted to better address this pathway of AR-signalling and to identify multiplex biomarker strategies including plasma AR and FCH-PET/CT in mCRPC patients.

Circulating cell-free AR and CYP17A1 copy number variations may associate with outcome of metastatic castration-resistant prostate cancer patients treated with abiraterone.

BACKGROUND: This study aimed to investigate copy number variations (CNVs) of CYP17A1 and androgen receptor (AR) genes in serum cell-free DNA collected before starting abiraterone in 53 consecutive patients with castration-resistant prostate cancer (CRPC). METHODS: Serum DNA was isolated and CNVs were analysed for AR and CYP17A1 genes using Taqman copy number assays. The association between CNVs and progression-free/overall survival (PFS/OS) was evaluated by the Kaplan-Meier method and log-rank test. RESULTS: Median PFS of patients with AR gene gain was 2.8 vs 9.5 months of non-gained cases (P < 0.0001). Patients with CYP17A1 gene gain had a median PFS of 2.8 months vs 9.2 months in the non-gained patients (P = 0.0014). A lower OS was reported in both cases (AR: P < 0.0001; CYP17A1: P = 0.0085). Multivariate analysis revealed that PSA decline ⩾ 50%, AR and CYP17A1 CNVs were associated with shorter PFS (P < 0.0001, P = 0.0004 and P = 0.0450, respectively), while performance status, PSA decline ⩾ 50%, AR CNV and DNA concentration were associated with OS (P = 0.0021, P = 0.0014, P = 0.0026 and P = 0.0129, respectively). CONCLUSIONS: CNVs of AR and CYP17A1 genes would appear to be associated with outcome of CRPC patients treated with abiraterone.

Low-grade central osteosarcoma: a difficult condition to diagnose.

Low-grade central osteosarcoma (LGCO) is a rare variant of osteosarcoma which is difficult to diagnose. If not treated appropriately, the tumour can recur with higher-grade disease. We reviewed our experience of this condition to try and identify factors that could improve both diagnosis and outcome. 18 patients out of 1540 osteosarcoma cases (over 25 years) had LGCO (1.2%). Only 11 patients (61%) were direct primary referrals. Almost 40% (7 of 18) cases were referred after treatment elsewhere when the diagnosis had not been made initially and all presented with local recurrence. Of the 11 who presented primarily, the first biopsy was diagnostic in only 6 (55%) cases. Of the remaining cases, up to three separate biopsies were required before a definitive diagnosis was made. Overall survivorship at 5 years was 90%. 17 patients were treated with limb salvage procedures, and one patient had an amputation. The diagnosis of LGCO remains challenging due to the relatively nonspecific radiological and histological findings. Since treatment of LGCO is so different to a benign lesion, accurate diagnosis is essential. Any difficult or nondiagnostic biopsies of solitary bone lesions should be referred to specialist tumour units for a second opinion.

Pneumonectomy: quality of life and long-term results.

AIM: Pneumonectomy is the standard surgery for resectable locally advanced lung cancer. Objectives of this study were: 1) to assess the overall survival; 2) to evaluate the pulmonary and cardiac function impairment; 3) to monitor quality of life (QoL) in a consecutive series of patients undergoing pneumonectomy, defining the potential risk factors of a poor prognosis. METHODS: From January 2003 to March 2010, 71 patients undergoing pneumonectomy for lung cancer or mesothelioma were prospectively enrolled in this study. Twenty-six patients underwent right pneumonectomy (2 of them underwent intrapericardial pneumonectomy), 31 left pneumonectomy (3 of them underwent intrapericardial pneumonectomy), 3 extended pneumonectomy, 3 extrapleural pneumonectomy and 5 patients underwent completion pneumonectomy. Three patients were not included in the study for early postoperative deaths (4.3%). All patients underwent complete preoperative assessment and one year after surgery. QoL was assessed by a questionnaire. RESULTS: One and five-year survival rate was 93% (N.=63) and 20% (N.=14), respectively. Mean values of FEV1 decreased from 2.59±0.75 L to 1.8±0.72 L (P<0.001). One year after surgery all patients showed moderate tricuspid valve insufficiency, PASP significantly higher and right ventricular free wall thickness moderately increased. An increased negative effect was recorded in the QoL scores with P<0.001. Three clinical and surgical parameters were identified as risk or protective factors for the survival outcome. CONCLUSION: Postoperative mortality (4.3%) and five-year survival (20%) after pneumonectomy seem to be satisfactory. Late cardiopulmonary insufficiency is uncommon and acceptable QoL is still achievable.

Increased expression of 5-lipoxygenase is common in clear cell renal cell carcinoma.

The clinical behaviour of Clear Cell Renal Cell Carcinoma (CC-RCC) is often unpredictable. To fully understand the signaling pathways involved in CC-RCC development, we examined whether the 5-Lipoxygenase (5-LO), which catalyzes the biosynthesis of proinflammatory leukotrienes, is involved in renal tumorigenesis. By analyzing 46 snap-frozen primary renal cell carcinomas and their corresponding normal renal cortex biopsies, 5-LO protein levels were found to be significantly increased in the majority of CC-RCCs (P<0.001). Quantitative 5-LO mRNA expression analysis revealed up to 3-fold increased expression in the tumor tissues. There was no association between 5-LO and gender, grade or vein invasion. In contrast, increased 5-LO protein and mRNA correlated with large tumor size (>4 cm) and age of patients (P<0.001). 5-LO was frequently overexpressed in von Hippel-Lindau protein (pVHL)-reduced tumors and in Vascular Endothelial Growth Factor (VEGF)-positive tumors, which represent two frequent alterations in CC-RCC. Cell culture experiments demonstrated that VEGF expression was strongly inducible by 5-LO metabolites in RCC cell lines. The loss of pVHL expression led to high basal 5-LO and VEGF expression, which were markedly reduced by transfection with 5-LO small interfering RNA (siRNA). These results suggest that 5-LO up-regulation is an important step in renal cancer progression.

[Levels of monokines in peripheral monocytes in patients with superficial tumors of the bladder treated with BCG. Results after 1- and 3-year follow-up]. / Livelli di monochine nei monociti periferici nei pazienti affetti da tumore superficiale della vescica trattati con BCG. Risultati ad uno e a tre anni di follow-up.

BCG has been shown in prospective randomized clinical trials to provide superior therapeutic results when composed to transurethral resection alone, or to adjuvant therapy with Thiotepa or Adriamicin. Even if the mechanism by which BCG mediate antitumor activity are not clearly established, an association between the immunological response and antitumoral activity is known IL-1 and TNF alfa are the monokines that have multiple biological effects, including linfocyte proliferation, production of fever, augmentation of cytotoxicity and production of cytokines. The goal of this study is show the response from LPS induced and not peripheral monocytes of superficial bladder cancer patients BCG treated and not, i.e. the levels of TNF alfa, IL-1 and not IL-6.

[Orthotopic continent urinary diversion according to Hautmann: 1989-1995. Physiopathologic, morphologic and urodynamic, metabolic considerations and follow-up]. / Derivazione urinaria continente ortotopica sec. Hautmann: 1989-1995. Considerazioni fisiopatologiche, morfologiche ed urodinamiche, metaboliche e follow up.

The orthotopic ileal neobladder is a completely detubularized, low pressure, high capacity reservoir created from the ileum without any valve. After cystoprostatectomy, a bowel segment of 40-60 cms is dissected free at a distance of 15 cms from the ileo-cecal valve. The bowel is detubularized and configurated in a cylinder. Then the neobladder is anatomized to the urethra and ureters. From 1989 to 1995 20 patients underwent ileal orthotopic urinary diversion according to Hautmann. Two patients died, the others are still disease free (mean follow up 36 months). The high capacity and low pressure allow a good continence control, while among metabolic alterations the most frequent is metabolic acidosis. The ileal neobladder represents a valid alternative to any form of cutaneous urinary diversion and is associated to a low incidence of complications.

Iron (III) stimulation of lipid hydroperoxide-dependent lipid peroxidation.

In an experimental system where both Fe2+ autoxidation and generation of reactive oxygen species is negligible, the effect of FeCl2 and FeCl3 on the peroxidation of phosphatidylcholine (PC) liposomes containing different amounts of lipid hydroperoxides (LOOH) was studied; Fe2+ oxidation, oxygen consumption and oxidation index of the liposomes were measured. No peroxidation was observed at variable FeCl2/FeCl3 ratio when PC liposomes deprived of LOOH by triphenylphosphine treatment were utilized. By contrast, LOOH containing liposomes were peroxidized by FeCl2. The FeCl2 concentration at which Fe2+ oxidation was maximal, defined as critical Fe2+ concentration [Fe2+]*, depended on the LOOH concentration and not on the amount of PC liposomes in the assay. The LOOH-dependent lipid peroxidation was stimulated by FeCl3 addition; the oxidized form of the metal increased the average length of radical chains, shifted to higher values the [Fe2+]* and shortened the latent period. The iron chelator KSCN exerted effects opposite to those exerted by FeCl3 addition. The experimental data obtained indicate the kinetics of LOOH-dependent lipid peroxidation depends on the Fe2+/Fe3+ ratio at each moment during the time course of lipid peroxidation. The results confirm that exogenously added FeCl3 does not affect the LOOH-independent but the LOOH-dependent lipid peroxidation; and suggest that the Fe3+ endogenously generated exerts a major role in the control of the LOOH-dependent lipid peroxidation.

[Role of echography in the diagnosis, screening, and follow-up of patients with von Hippel-Lindau syndrome]. / Ruolo dell'ecografia nella diagnosi, nello screening e nel follow-up dei pazienti affetti da sindrome di von Hippel-Lindau.

Von Hippel-Lindau (VHL) disease is a genetic disorder characterized by hemangioblastomas of the brain and spinal cord, retinal angiomas, pancreatic cysts, pheochromocytomas, epididymal cystadenomas and renal cysts and neoplasms. These disease is transmitted in an autosomal dominant fashion and the gene associated with transmission of VHL has been localized to the 3p25-3p26 region of chromosome 3. In this study we examined a family with von Hippel-Lindau disease established of mother and three children and five progeny. These patients were evaluated with urinary tract echography, computerized tomography, DNA sequencing with polymerase chain reactions (PCR) and SSCP analysis. The ultrasonography is utilized to diagnosis, screening and in the follow-up of undergone surgery patient's. With this study we examined the role of echography in patients with von Hippel-Lindau disease.

Intrinsic fluorescence properties and structural analysis of p13(suc1) from Schizosaccharomyces pombe.

p13(suc1) acts in the fission yeast cell division cycle as a component of p34(cdc2). In the present work, structural information contained in the intrinsic fluorescence of p13(suc1) has been extracted by steady-state and time-resolved fluorescence techniques. In its native form, the steady-state emission spectrum of p13(suc1) is centered at 336 nm. Upon denaturation by guanidine HCl (4.0 M), the emission spectrum is shifted to 355-360 nm and the fluorescence intensity decreases 70%. The same changes are not obtained with p13(suc1) at 56 degrees C or after incubation at 100 degrees C, and the protein appears to be substantially temperature-stable. The fluorescence decay of p13(suc1) is best described by three discrete lifetimes of 0.6 ns (tau1), 2.9 ns (tau2), and 6.1 ns (tau3), with amplitudes that are dependent on the native or unfolded state of the protein. Under native conditions, the two predominant decay-associated spectra, DAS-tau2 (lambdamax = 332 nm) and DAS-tau3 (lambdamax = 340 nm), derive from two different excitation DAS. Moreover distinct quenching mechanisms and collisional accessibilities (kq(tau2)>>kq(tau3)) are resolved for each lifetime. An interpretation in terms of specific tryptophan residue (or protein conformer)-lifetime assignments is presented. The decay of the fluorescence anisotropy of native p13(suc1) is best described by a double exponential decay. The longer correlation time recovered (9 ns

2-Naphthol-phosphatidylethanolamine: A fluorescent phospholipid analogue for excited-state proton transfer studies in membranes.

The fluorescence properties of the phospholipid derivative,N-[1-(2-naphthol)]-phosphatidylethanolamine (NAPH-PE), have been studied by steady-state and time-resolved fluorescence techniques. The new probe is a naphthol adduct of phosphatidylethanolamine. The emission spectrum of the fluorescent phospholipid depends on the pH and on the proton acceptor concentration as expected for a typical two-state excited-state proton transfer reaction. In ethanol solutions at an apparent pH of 6.7 and in the presence of acetate anion (0.14M), a biexponential decay is obtained from global analysis of the data. The lifetimes,τ 1=3.9 ns andτ 2=6.2 ns. are constant across the spectral region 350-460 nm. The decay-associated spectra and the species-associated spectra reproduce well the profiles reported for a two-state excited-state proton transfer reaction. The fluorescent phospholipid has been incorporated into dimyristoyllecithin and dipalmitoyllecithin vesicles. Although lower proton transfer is found, the reaction appears to be dependent on the gel-to-liquid-crystalline phase transition of the lipid membrane. In addition, the steady-state anisotropy of NAPH-PE measured as a function of temperature trace the phase transition of the two vesicle systems. Thus, it is shown that the physical state of the bilayer affects a reaction which takes place at the membrane surface. In the presence of acetate ions (0.3M), global analysis, performed in terms of fluorescence decay parameters, recovers preexponential coefficients that are consistent with an excited-state proton transfer reaction. The short lifetime drops from 3.9 to 0.44 ns without significant changes of the longer-lifetime component.

Preparation of lucifer yellow fluorescent liposomes: A method for cells' membrane labeling.

This report describes a method to conjugate lucifer yellow to the external surface of liposomes. The heterobifunctional cross-linking reagentN-succinimidyl 3-(2-pyridyldithio)propionate has been used to activate DMPE molecules. The DMPE-dithiopyridine product has been mixed with DMPC to prepare liposome vesicles. These have been reduced by DTT and finally reacted with lucifer yellow-iodoacetamide to produce the fluorescence-labeled vesicles. The quenching of their fluorescence intensity by Kl is consistent with fully exposed fluorophores. The decay of the fluorescence intensity of the lipid-bound lucifer yellow is biexponential (τ1=7.9 ns; τ2=1.1 ns), with a relative yield of 0.16. When the fluorescent liposomes are mixed with cells, the lucifer yellow-DMPE derivative is transferred. Boar spermatozoa and peripheral human blood lymphocytes have been used as cellular models. The extent of incorporation is dependent on the incubation time and temperature. At 36°C, lucifer yellow fluorescence appears in the spermatozoa cells after 10 min of incubation and reaches its maximum at about 60 min. The fluorescent phospholipid derivative seems to incorporate specifically into membrane structures. The highest labeling ratio is observed with integer, scarcely motile, spermatozoa. A poorer labeling yield (≈15%) is found with lymphocytes. Interestingly, photobleaching due to epiillumination of the labeled cells is apparently negligible and cells are clearly visible after irradiation times ranging from several minutes to few hours.

[Use of nabumetone in the treatment of primary dysmenorrhea. Report of 100 cases]. / Impiego di nabumetone nel trattamento della dismenorrea primaria. Descrizione di 100 casi.

The aim of the study was to assess the efficacy and tolerability of nabumetone, a new nonsteroid anti-inflammatory agent with analgesic and antipyretic functions, in the treatment of primary dysmenorrhea in 100 patients. Treatment was administered at a dose of 1 g per day for slight and moderate cases and 2 g per day for severe forms, starting from the onset of painful symptoms and lasting while they persisted. Side effects were observed in 7% of cases but were limited to the gastroenteric tract. The analysis of results confirms that with regard to the remission of symptoms, treatment was efficacious from the second month and that a further improvement was obtained with continued treatment. However, the Authors observed that, although the remission of symptoms was partial in the majority of cases, there was a greater response in cases of moderate or severe dysmenorrhea and their duration was shorter in comparison to those months in which patients had not received nabumetone treatment.

[Use of phytostimolin vaginal cream and lavage in cervical dystrophy after DTC of the cervix]. / Impiego di fitostimoline crema e lavanda vaginale nella distrofia cervicale e dopo DTC della portio. Valutazione in doppio cieco di 60 casi.

The study evaluated the efficacy and tolerance of the active components of "phytostimolin" cream and vaginal lavage, Triticum Vulgare and Ether glycoethylen-mono-phenolic, in 40 patients suffering from dystrophic cervico-vaginal pathologies (group 1), and in 20 patients following DTC of the portio due to ectropion (group 2). The study was double blind. An overall efficacy of 70% was observed in group 1 and 90% in group 2. The results obtained, the absence of side effects, and the good level of tolerance confirm the value of the above components in the pathology in question.

[The use of ferritin in 40 patients with iron deficiency of various degrees caused by gynecologic disorders]. / Impiego di ferritina in 40 pazienti affette da sideropenia di vario grado da cause ginecologiche.

The authors evaluated the efficacy and tolerability of treatment with ferritin in 40 cases of iron deficiency because of gynecological pathology. After 2 months of therapy, 80% of patients showed a normalization of laboratory examinations while after 4 months both the normalization of laboratory examinations and the clinical symptomatology, were demonstrated in all cases. Only 7.5% of cases were very light and did not show remarkable adverse. It is concluded that this can be used safely.

[Endometriosis of the lower abdominal wall. Report of two cases secondary to cesarean section]. / Endometriosi della parete addominale inferiore. Descrizione di due casi secondari a taglio cesareo.

The paper describes two cases of cutaneous endometriosis in correspondence with the surgical scar following cesarean section. The cases formed part of a series of 500 abdominal operations performed during the period 1988-89, of which about 200 were cesarean sections, with a 1% frequency. In line with the hypothesis regarding the spread of endometrial tissue during surgery and with that concerning peritoneal metaplasia, the authors recommend paying special attention during the technical procedure of extracting the fetus, and performing an introflexed suture of the uterine incision and of the parietal peritoneum.

[Comparison of fluconazole and ketoconazole in the therapy of vaginal candidiasis by administration in two different oral doses]. / Confronto tra Fluconazolo e Ketoconazolo nella terapia orale della candidosi vaginale in due differenti modalità di somministrazione.

The authors examined 20 patients affected by vaginal candidiasis and evaluated the efficacy and tolerability of treatment with Fluconazole in comparison with Ketoconazole, using two different doses of oral administration: Fluconazole, 150 mg in a single dose; Ketoconazole, 400 mg/die for 5 days. There were no significant differences in results; adverse effects were insignificant and the level of efficacy, which was the same in both cases, was high. In conclusion, both molecules are confirmed to be efficacious, although patients showed a preference for the single dose and for only one day of therapy.

[Use of ofloxacin in 45 cases of infection of the lower urinary tract in women]. / Impiego di ofloxacina in 45 casi di infezioni del tratto urinario inferiore femminile.

Forty-five female patients affected by lower urinary tract infections without secondary complications were examined. Ofloxacin was administered in three different dosages in order to evaluate drug efficacy and tolerance: 600 mg/day for 3 days in 22 cases; 300 mg/day for 3 days in 22 cases; 600 mg/day for 5 days in 1 case. Adverse effects were insignificant; clinical remission was virtually complete and urine tests proved negative in 98% of cases. On the basis of these findings it is possible to state that Ofloxacin therapy is efficacious in lower urinary tract infections without secondary complications in women.

[A case of pulmonary embolism after cesarean section]. / Su di un caso di embolia polmonare dopo taglio cesareo.

The authors describe a case of pulmonary embolism occurred to a young woman (24 years old) after a Cesarean operation. All the evolving stages of the disease are examined till to the complete recovery of the patient. They conclude underlining the importance of an opportune diagnoses and an adequate therapy for a favourable prognoses quoad vitam et valetitudinem.