Very Rapid Improvement in Extended Nitric Oxide Parameters Is Associated With Clinical and Functional Improvement in Patients With Chronic Rhinosinusitis With Nasal Polyps Treated With Dupilumab.

BACKGROUND AND OBJECTIVE: Dupilumab, an anti-IL-4 receptor a monoclonal antibody, was recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate-to-severe asthma. Onset of its clinical effects is rapid. CRSwNP is characterized by extended type 2 inflammatory involvement that can be assessed using extended nitric oxide analysis. We investigated whether dupilumab was associated with a rapid improvement in extended nitric oxide parameters, lung function, and clinical outcomes in patients with CRSwNP. METHODS: Consecutive patients with CRSwNP and an indication for dupilumab were evaluated for extended nitric oxide analysis (exhaled, FeNO; bronchial, JawNO; alveolar, CalvNO; nasal, nNO) and lung function 15 and 30 days after initiation of treatment and for clinical outcomes (nasal polyps score [NPS], quality of life questionnaires, visual analog scale [VAS] for the main symptoms, and the Asthma Control Test [ACT]) 30 days after initiation of treatment. RESULTS: We enrolled 33 patients. All extended nitric oxide and lung function parameters improved significantly after 15 days of treatment, remaining stable at 30 days. Scores on the NPS, VAS for the main RSwNP symptoms, quality of life questionnaires, and the ACT improved significantly 30 days after initiation of treatment. CONCLUSION: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway areas. This is associated with improved lung function and clinical parameters in patients with CRSwNP.

Neuronavigated Retropharyngeal Anterior Screw Fixation of the Odontoid for the Treatment of C2 Type II Fractures: Case Report.

Odontoid fractures, frequently observed in patients over the age of 70, often involve the base of the axis (Anderson-D'Alonzo type 2). For surgical treatment, posterior C1-C2 fixation is the traditional method, whose fusion rates range between 93 and 100%. However, morbidity and mortality rates are high. In addition, cervical motion, especially axial rotation, is postoperatively reduced. Nakanishi and Bohler introduced the anterior screw fixation approach for the surgical treatment of odontoid fracture type II. This procedure preserves the atlantoaxial complex motion, provides immediate stability and high fracture healing rates, and, most importantly, has a low incidence of complications with good fusion rates. The surgical strategy must take into account the patient's anatomy, the morphological characteristics of the fracture, the quality of the bone, and any concomitant injuries. In this chapter, we describe a C2 type II fracture treated via a neuronavigated anterior retropharyngeal approach.

Correlation Between Cervical Spine Sagittal Alignment and Clinical Outcome After Standalone Intersomatic Titanium Cage CeSPACE for Cervical Anterior Discectomy and Fusion in Cervical Degenerative Disk Diseases.

The aim of this study was to determine the relationship between cervical spine sagittal alignment and clinical outcomes after using a standalone intersomatic titanium cage CeSPACE for anterior cervical discectomy and arthrodesis. We present our clinical experience in a group of 180 patients with a mean follow-up for at least 2 years. Patients were evaluated by clinical and radiological assessment preoperatively, immediately after surgery and at regular follow-up. There were 97 male and 83 female patients (average age: 56.6 years) who were preoperatively affected by cervical radiculomyelopathy that was due to spondylosis or cervical disk herniation and who underwent surgical treatment. All patients underwent an anterior discectomy and interbody fusion through the positioning of one or more levels of the CeSPACE device. Compared with the preoperative scores, improvement was seen in postoperative visual analog scale (VAS) scores and Neck Disability Index (NDI) values. The standalone intersomatic titanium cage CeSPACE for anterior cervical discectomy and arthrodesis improved radiculomyelopathy and increased the probability of cervical kyphotic alignment. However, cervical sagittal alignment after surgery was not significantly associated with clinical outcomes in terms of postoperative improvement in VAS scores and NDI values. Similarly, the change in cervical sagittal alignment was not related to visual analog scale scores or Neck Disability Index values.

Very rapid improvement of extended nitric oxide parameters, associated with clinical and functional betterment, in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) treated with Dupilumab.

BACKGROUND AND OBJECTIVE: Background: Dupilumab, an anti-IL-4 receptor alpha monoclonal antibody, has been recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate to severe asthma, demonstrating a rapid onset of clinical effects. CRSwNP is characterized by an extended type-2 inflammatory involvement that can be assessed by extended nitric oxide analysis. Objective: In this study we investigated whether Dupilumab is associated with a rapid improvement in extended nitric oxide parameters, lung function and clinical outcomes in patients with CRSwNP. METHODS: : Consecutive patients with CRSwNP and indication to be treated with Dupilumab were evaluated for extended nitric oxide analysis (exhaled, FENO; bronchial, JawNO and alveolar, CalvNO components; nasal, nNO) and lung function 15 and 30 days after treatment initiation, and for clinical outcomes (nasal polyps score, NPS; quality of life questionnaires; visual analogue scales, VAS, for main symptoms, asthma control test, ACT) after 30 days of treatment initiation. RESULTS: 33 patients were enrolled. All extended nitric oxide and lung function parameters significantly improved after 15 days of treatment remaining stable at 30 days. NPS, VAS for main CRSwNP symptoms, quality of life questionnaires and ACT significantly improved after 30 days of treatment initiation. CONCLUSION: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway districts and this is associated with improved lung function and clinical parameters in patients with CRSwNP.

Stereoscopically Observing Manipulative Actions.

The purpose of this study was to investigate the contribution of stereopsis to the processing of observed manipulative actions. To this end, we first combined the factors "stimulus type" (action, static control, and dynamic control), "stereopsis" (present, absent) and "viewpoint" (frontal, lateral) into a single design. Four sites in premotor, retro-insular (2) and parietal cortex operated specifically when actions were viewed stereoscopically and frontally. A second experiment clarified that the stereo-action-specific regions were driven by actions moving out of the frontoparallel plane, an effect amplified by frontal viewing in premotor cortex. Analysis of single voxels and their discriminatory power showed that the representation of action in the stereo-action-specific areas was more accurate when stereopsis was active. Further analyses showed that the 4 stereo-action-specific sites form a closed network converging onto the premotor node, which connects to parietal and occipitotemporal regions outside the network. Several of the specific sites are known to process vestibular signals, suggesting that the network combines observed actions in peripersonal space with gravitational signals. These findings have wider implications for the function of premotor cortex and the role of stereopsis in human behavior.

A human homologue of monkey F5c.

Area F5c is a monkey premotor area housing mirror neurons which responds more strongly to grasping observation when the actor is visible than when only the actor's hand is visible. Here we used this characteristic fMRI signature of F5c in seven imaging experiments - one in macaque monkeys and six in humans - to identify the human homologue of monkey F5c. By presenting the two grasping actions (actor, hand) and varying the low level visual characteristics, we localized a putative human homologue of area F5c (phF5c) in the inferior part of precentral sulcus, bilaterally. In contrast to monkey F5c, phF5c is asymmetric, with a right-sided bias, and is activated more strongly during the observation of the later stages of grasping when the hand is close to the object. The latter characteristic might be related to the emergence, in humans, of the capacity to precisely copy motor acts performed by others, and thus imitation.

The overlap of the EBA and the MT/V5 cluster.

The extrastriate body area (EBA) is located in the lateral occipito-temporal cortex, in the vicinity of the motion-sensitive region hMT/V5+. To investigate the relationship of EBA to the recently mapped retinotopic areas of the MT/V5 cluster (Kolster et al., 2010), we evaluated the proportion of voxels responsive to the presentation of static human bodies (EBA voxels) in each of the four areas of the MT/V5 cluster and neighboring LO and phPIT areas. We evaluated this proportion as both a function of the number of voxels in a given area and the total number of voxels in a broader lateral occipito-temporal cortex (LOTC) ROI. We observed that each of the four retinotopic areas of the MT/V5 cluster includes substantial fractions of EBA voxels, in contrast to the LO and phPIT areas. This proportion was slightly greater in the right than left hemisphere, and did not depend on the control condition. While most EBA voxels in MT/V5 were only body-sensitive, those in pMSTv and pFST were also motion-sensitive. The main locus of EBA voxels outside the MT/V5 cluster was in the LOTC cortex just rostral to the MT/V5 cluster. Although this region contained more EBA voxels than the MT/V5 cluster, the proportion as a function of areal size was much reduced compared to the MT/V5 cluster. Our results show that EBA is not a single cortical area as EBA voxels are located in all four areas of the MT/V5 cluster, and that body-sensitivity is a key feature of the MT/V5 cluster, in keeping with its exquisite sensitivity to observed actions of others.

Identification and functional analysis of fructosyl amino acid-binding protein from Gram-positive bacterium Arthrobacter sp.

AIM: Fructosyl amino acid-binding protein (FABP) is a substrate-binding protein (SBP), which recognizes fructosyl amino acids (FAs) as its ligands. Although FABP has been shown as a molecular recognition tool of biosensing for glycated proteins, the availability of FABP is still limited and no FABP was reported from Gram-positive bacteria. In this study, a novel FABP from Gram-positive bacteria, Arthrobacter spp., was reported. METHOD AND RESULTS: BLAST analysis revealed that FABP homologues exist in some of Arthrobacter species genomes. An FABP homologue cloned from Arthrobacter sp. FV1-1, FvcA, contained a putative lipoprotein signal sequence, suggesting that it is a lipoprotein anchored to the bacterial cytoplasmic membrane, which is a typical characteristic for SBPs from Gram-positive bacteria. In contrast, FvcA also exhibits high amino acid sequence similarity to a known Gram-negative bacterial FABP, which exists as a free periplasmic protein. FvcA, without the N-terminal anchoring region, was then recombinantly produced as soluble protein and was found to exhibit Nα-FA-specific binding activity by intrinsic fluorescent measurement. CONCLUSION: This study identified a novel FABP from a Gram-positive bacterium, Arthrobacter sp., which exhibited Nα-FA-specific binding ability. This is the first report concerning an FABP from a Gram-positive bacterium, suggesting that FABP-dependent FA catabolism system is also present in Gram-positive bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: The novel FABP exhibits the ability to specifically bind to Nα-FA with a high affinity. This selectivity is beneficial for applying FABP in HbA1c sensing. The successful preparation of water-soluble, functionally expressed Gram-negative bacterial FABP may make way for future applications for a variety of SBPs from Gram-positive bacteria employing the same expression strategy. The results obtained here enhance our understanding of bacterial FA catabolism and contribute to the improved development of FABP as Nα-FA-sensing molecules.

A case of Leishmania infection with focal splanchnic involvement without systemic symptoms: a potential anti-inflammatory role for vitamin D.

CASE REPORT: We report the case of a 59 year-old woman with persistent nausea, hyporexia, fatigue and mild abdominal discomfort. The patient was hospitalized upon suspicion of malignancy due to multiple hepatic and splenic nodules found on an abdominal ultrasound. Hypercalcemia emerged at initial diagnostic workup, which was considered secondary to iatrogenic vitamin D intoxication. After an adequate management of hypercalcemia and normalization of serum calcium level, all symptoms presented by the patient completely regressed. In order to characterize splanchnic lesions, several biochemistry, microbiology and radiological tests were performed, including two bioptic specimens of a focal hepatic lesion. Eventually, a diagnosis of leishmanial infection was made. The patient started a specific anti-leishmanial treatment, and the focal hepatic and splenic lesions progressively disappeared. CONCLUSION: To our knowledge, this is the first reported case of asymptomatic leishmanial infection with a widespread focal splanchnic involvement. The anti-inflammatory effect of vitamin D could be related to this atypical presentation of visceral leishmaniasis without systemic symptoms.

An investigation into the cytotoxic effects of microbubbles and their constituents on osteosarcoma and bone marrow stromal cells.

BACKGROUND: Ultrasound-responsive microbubbles offer a means of achieving minimally invasive, localised drug delivery in applications including regenerative medicine. To facilitate their use, however, it is important to determine any cytotoxic effects they or their constituents may have. The aim of this study was to test the hypothesis that phospholipid-shelled microbubbles are non-toxic to human bone-derived cells at biologically-relevant concentrations. METHODS: Microbubbles were fabricated using combinations of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dibehenoyl-sn-glycero-3-phosphocholine (DBPC), polyoxyethylene(40) stearate (PEG40S) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene-glycol)-2000] (DSPE-PEG2000). Microbubble size and concentration were measured as a function of time and temperature by optical microscopy. Effects on MG63 osteosarcoma and human bone marrow stromal cells (BMSCs) were measured for up to 72 h by assay for viability, metabolic activity and proliferation. RESULTS: DBPC:DSPE-PEG2000 microbubbles were significantly more stable than DSPC:PEG40S microbubbles under all conditions tested. Serum-containing medium had no detrimental effect on microbubble stability, but storage at 37 °C compared to at 4 °C reduced stability for both preparations, with almost complete dissolution of microbubbles at times ≥24 h. DSPC:PEG40S microbubbles had greater inhibitory effects on cell metabolism and growth than DBPC:DSPE-PEG2000 microbubbles, with PEG40S found to be the principle inhibitory component. These effects were only evident at high microbubble concentrations (≥20% (v/v)) or with prolonged culture (≥24 h). Increasing cell-microbubble contact by inversion culture in a custom-built device had no inhibitory effect on metabolism. CONCLUSIONS: These data indicate that, over a broad range of concentrations and incubation times, DBPC:DSPE-PEG2000 and DSPC:PEG40S microbubbles have little effect on osteoblastic cell viability and growth, and that PEG40S is the principle inhibitory component in the formulations investigated.

[Modalities for access to networks of palliative care and pain management in Lazio: level of information for health personnel aware of the Policlinico Tor Vergata]. / Modalità per l'accesso alle reti di cure palliative e terapia del dolore nel Lazio: grado di informazione del personale sanitario del Policlinico Tor Vergata.

Law no. 38 of 2010 introduces for the first time protection for access to Palliative Care and Pain Management. It was interesting to evaluate the level of knowledge among health care workers at the Policlinico Tor Vergata, procedures relating to such access through the administration of a questionnaire. The questionnaire divided into a general part and the two sections (A and B) The general part concerns the health operator respect to age, gender, profession, and his role within the operating unit of the hospital. The section A and B, is to understand if the operator knows Palliative Care, and Pain Therapy, as he became aware of the two arguments, and if they have been addressed during the university courses he attended. The analysis of the data examined show a general confusion distributed evenly among all professionals. Is greater knowledge of pain therapy compared to Palliative Care.

Comorbid allergic rhinitis and asthma: important clinical considerations.

INTRODUCTION: The numerous links between allergic rhinitis and asthma have been extensively explored in the last two decades, gaining great concern within the scientific community. These two conditions frequently coexist in the same patient and share numerous pathogenetic and pathophysiological mechanisms. AREAS COVERED: We reviewed major pathophysiological, epidemiological, and clinical links between allergic rhinitis and asthma. We also provided a comprehensive discussion of allergic rhinitis treatment according to current guidelines, with a particular focus on the relevance of allergic rhinitis therapies in patients with comorbid asthma. EXPERT OPINION: We believe that there are several unmet needs for our patients, however, there are promising advances forecasted for the future. Although allergic rhinitis is a recognized risk factor for asthma, a proper asthma detection and prevention plan in allergic rhinitis patients is not available. Allergen immunotherapy (AIT) represents a promising preventive strategy and may deserve an earlier positioning in allergic rhinitis management. A multidisciplinary approach should characterize the journey of patients with respiratory allergies, with an adequate referral to specialized Allergy/Asthma centers. Molecular Allergy Diagnosis may provide support for optimal AIT use. Finally, a possible evolution of biological treatment can be envisaged, mainly if biosimilars decrease such therapies' costs.

Cylindrical implosion platform for the study of highly magnetized plasmas at Laser MegaJoule.

Investigating the potential benefits of the use of magnetic fields in inertial confinement fusion experiments has given rise to experimental platforms like the Magnetized Liner Inertial Fusion approach at the Z-machine (Sandia National Laboratories) or its laser-driven equivalent at OMEGA (Laboratory for Laser Energetics). Implementing these platforms at MegaJoule-scale laser facilities, such as the Laser MegaJoule (LMJ) or the National Ignition Facility (NIF), is crucial to reaching self-sustained nuclear fusion and enlarges the level of magnetization that can be achieved through a higher compression. In this paper, we present a complete design of an experimental platform for magnetized implosions using cylindrical targets at LMJ. A seed magnetic field is generated along the axis of the cylinder using laser-driven coil targets, minimizing debris and increasing diagnostic access compared with pulsed power field generators. We present a comprehensive simulation study of the initial B field generated with these coil targets, as well as two-dimensional extended magnetohydrodynamics simulations showing that a 5 T initial B field is compressed up to 25 kT during the implosion. Under these circumstances, the electrons become magnetized, which severely modifies the plasma conditions at stagnation. In particular, in the hot spot the electron temperature is increased (from 1 keV to 5 keV) while the density is reduced (from 40g/cm^{3} to 7g/cm^{3}). We discuss how these changes can be diagnosed using x-ray imaging and spectroscopy, and particle diagnostics. We propose the simultaneous use of two dopants in the fuel (Ar and Kr) to act as spectroscopic tracers. We show that this introduces an effective spatial resolution in the plasma which permits an unambiguous observation of the B-field effects. Additionally, we present a plan for future experiments of this kind at LMJ.

Spent coffee ground characterization, pelletization test and emissions assessment in the combustion process.

Industrial development and increased energy requirements have led to high consumption of fossil fuels. Thus, environmental pollution has become a profound problem. Every year, a large amount of agro-industrial, municipal and forest residues are treated as waste, but they can be recovered and used to produce thermal and electrical energy through biological or thermochemical conversion processes. Among the main types of agro-industrial waste, soluble coffee residues represent a significant quantity all over the world. Silver skin and spent coffee grounds (SCG) are the main residues of the coffee industry. The many organic compounds contained in coffee residues suggest that their recovery and use could be very beneficial. Indeed, thanks to their composition, they can be used in the production of biodiesel, as a source of sugar, as a precursor for the creation of active carbon or as a sorbent for the removal of metals. After a careful evaluation of the possible uses of coffee grounds, the aim of this research was to show a broad characterization of coffee waste for energy purposes through physical and chemical analyses that highlight the most significant quality indexes, the interactions between them and the quantification of their importance. Results identify important tools for the qualification and quantification of the effects of coffee waste properties on energy production processes. They show that (SCG) are an excellent raw material as biomass, with excellent values in terms of calorific value and low ash content, allowing the production of 98% coffee pellets that are highly suitable for use in thermal conversion systems. Combustion tests were also carried out in an 80kWth boiler and the resulting emissions without any type of abatement filter were characterized.

Stark broadening of hydrogen lines in low-density magnetized plasmas.

Stark broadening of hydrogen lines in the presence of a magnetic field is revisited, with emphasis on the role of the ion component under typical conditions of magnetized fusion devices. An impact theory for ions valid at low density (N_{e} < or approximately 10;{14} cm;{-3}) and taking into account the Zeeman degeneracy removal of the atomic states is developed. It is shown that the Stark widths of the Lorentz triplet components strongly depend on the magnetic field. The model is validated by a computer simulation method. For the lateral sigma components of Lyalpha , we show that the impact approximation still holds for densities as high as N_{e} approximately 10;{15} cm;{-3}. In contrast, for the central pi component as well as for the other lines from low principal quantum number, significant discrepancies between the proposed theory and the simulation results appear at high density. Application to Dalpha in tokamak divertor plasma conditions shows that, in this case, the quasistatic approximation becomes more relevant.

Vitamin D and disease severity in bronchiectasis.

BACKGROUND: Bronchiectasis is a complex respiratory disease characterised by permanent dilatation of bronchi. Vitamin D plays a role in infective disease by modulating the inflammation. Patients affected by bronchiectasis are frequently Vitamin D deficient and it correlates with lung function decline. We want to understand if there is a correlation between Vitamin D and clinical and radiological severity of bronchiectasis. METHODS: We included 57 patients (17 males/40 female with mean age 60 ±â€¯12 years) between October 2017 and March 2018. We excluded patients with cystic fibrosis, traction bronchiectasis and reporting Vitamin D supplementation. Bronchiectasis severity index (BSI) and Bhalla score were calculated, blood inflammatory markers and Vit. D were measured and lung function tests were performed. RESULTS: Vitamin D is deficient in 64% of patients, sufficient in 36% and normal in 7%. Mean BSI is 7.5 ±â€¯5 and mean Bhalla score is 16 ±â€¯4. Vitamin D levels correlate with Bhalla score (R2 = 0.68, p < 0.001) and BSI (R2 = 0.58, p < 0.0001). The correlation appears to be stronger than other markers of inflammation such as ESR and CRP [R2 = 0.33, p = 0.001 and R2 = 0.39, p = 0.001 respectively]. CONCLUSIONS: We consider Vitamin D as a good predictor of clinical and radiological severity of bronchiectasis.

Antibodies to SS-A/Ro-52kD and centromere in autoimmune liver disease: a clue to diagnosis and prognosis of primary biliary cirrhosis.

BACKGROUND: Primary biliary cirrhosis (PBC) may be associated with various rheumatological disorders. AIM: To investigate the frequency and significance of 'rheumatological' antinuclear antibodies in the field of autoimmune chronic liver disease, with special regard to PBC. METHODS: We studied 105 patients with PBC, 162 autoimmune liver disease controls (type 1 and 2 autoimmune hepatitis, primary sclerosing cholangitis), 30 systemic lupus erythematosus and 50 blood donors. Sera were tested for the presence of antibodies to extractable nuclear antigens (anti-ENA) by counterimmunoelectrophoresis, enzyme-linked and immunoblot (IB) assay, and for the presence of anti-centromere antibodies (ACA) by indirect immunofluorescence on HEp-2 cells and IB. RESULTS: The overall prevalence of IB-detected anti-ENA in PBC (30%) was higher than in type 1 autoimmune hepatitis (2.5%, P < 0.0001), type 2 autoimmune hepatitis (0%, P < 0.0001) and primary sclerosing cholangitis (11.5%, P = 0.006) and lower than in systemic lupus erythematosus (53%, P = 0.03). The most frequent anti-ENA reactivity in PBC was anti-SSA/Ro-52kD (28%). ACA were detected by IB in 21% PBC patients and never in the other subjects (P < 0.0001). Anti-SS-A/Ro/52kD positive PBC patients had at the time of diagnosis a more advanced histological stage (P = 0.01) and higher serum levels of bilirubin (P = 0.01) and IgM (P = 0.03) compared with negative ones. CONCLUSIONS: In the autoimmune liver disease setting, anti-SS-A/Ro-52kD and ACA have a high specificity for PBC and can thus be of diagnostic relevance in anti-mitochondrial antibodies negative cases. If confirmed in further studies with adequate follow-up, anti-SS-A/Ro-52kD antibodies might identify PBC patients with a more advanced and active disease.

Antinuclear antibodies giving the 'multiple nuclear dots' or the 'rim-like/membranous' patterns: diagnostic accuracy for primary biliary cirrhosis.

BACKGROUND: Serum antinuclear antibodies giving the 'multiple nuclear dots' or the 'rim-like/membranous' patterns are frequently detected by indirect immunofluorescence on HEp-2 cells in patients with primary biliary cirrhosis. AIM: To assess the accuracy of multiple nuclear dot and rim-like/membranous antinuclear antibodies for the diagnosis of primary biliary cirrhosis. METHODS: Sera from 4371 consecutive patients referred to our laboratory were analysed under code for antinuclear antibodies testing by indirect immunofluorescence on HEp-2 cells. RESULTS: Review of the clinical records of the 4371 patients allowed identification of 101 patients with antimitochondrial antibody-positive primary biliary cirrhosis and 22 with antimitochondrial antibody-negative variant. Multiple nuclear dot and/or rim-like/membranous patterns were found in 59 (1.3%) of the 4371 patients: 31 antimitochondrial antibody-positive primary biliary cirrhosis, 17 antimitochondrial antibody-negative primary biliary cirrhosis and 11 non-primary biliary cirrhosis. The specificity for primary biliary cirrhosis of both the antinuclear antibodies pattern was 99%. Positive predictive value and likelihood ratio for a positive test were 86% (95% CI: 72.7-94) and 221 (95% CI: 91.7-544) for multiple nuclear dot, 79% (95% CI: 62.2-90.1) and 132 (95% CI: 56.8-312.7) for rim-like/membranous, respectively. CONCLUSIONS: Multiple nuclear dot and rim-like/membranous antinuclear antibodies are rare findings. Their positivity strongly suggests the diagnosis of primary biliary cirrhosis, irrespective of antimitochondrial antibody status. The high specificity for primary biliary cirrhosis makes them a useful diagnostic tool especially in antimitochondrial antibody-negative patients.

Interferon adjuvant to radical nephrectomy in Robson stages II and III renal cell carcinoma: a multicentric randomized study.

PURPOSE: Because interferon gave promising results in the management of metastatic renal cell carcinoma in the 1980s, a multicentric randomized controlled trial was planned to compare adjuvant recombinant interferon alfa-2b (rIFNalpha2b) with observation after radical nephrectomy in patients with Robson stages II and III renal cell carcinoma. Overall and event-free survival were to be evaluated together with prognostic factors. PATIENTS AND METHODS: Overall and event-free survival curves for 247 patients (124 controls and 123 treated) were estimated by the Kaplan-Meier method and compared using the log-rank test. Cox's multiple regression models were adopted to perform a joint analysis of treatment and prognostic factors. RESULTS: The 5-year overall and event-free survival probabilities were 0.665 and 0.671, respectively, for controls and 0.660 and 0.567, respectively, for the treated group; the differences were not statistically significant (2P = .861 for overall and 2P = .107 for event-free survival with the log-rank test). Regarding prognostic factors, only grade, pT, and pN demonstrated a significant prognostic role. First-order interactions of treatment with pT and pN category were investigated; a significant interaction was found between pN and treatment. A harmful effect of rIFNalpha2b in the 97 treated pN0 patients and a protective effect in the 13 treated pN2/pN3 patients were statistically significant. CONCLUSION: Adjuvant rIFNalpha2b is not indicated after radical nephrectomy for renal cell carcinoma. The protective effect in the small group of pN2/pN3 patients requires further investigation.

Expression, purification and crystallization of the Vibrio harveyi acyltransferase.

We have obtained X-ray quality single crystals of Vibrio harveyi acyltransferase. The protein was obtained from V. harveyi by a gene mobilization expression system. The crystals are monoclinic (space group P2(1), a = 89.9 A, b = 83.6 A, c = 47.1 A, beta = 97.3 degrees) with two molecules related by a pronounced non-crystallographic dyad in the asymmetric unit, with a solvent content of approximately 50%. The diffraction pattern from fresh crystals extends beyond 2 A resolution using sealed tube CuK alpha radiation. The elucidation of the three-dimensional structure of this enzyme, believed to contain a proteinase-like catalytic triad, which resembles in many ways other eukaryotic fatty acid chain terminating enzymes, may have important consequences for our understanding of the molecular basis of the final stages of the synthesis of fatty acids.