Multi-center study on overall clinical complexity of patients with prolonged disorders of consciousness of different etiologies.

Aim: to assess overall clinical complexity of patients with acquired disorders of consciousness (DoC) in vegetative state/unresponsive wakefulness syndrome (VS/UWS) vs. minimally conscious state- MCS) and in different etiologies..Design: Multi-center cross-sectional observational study.Setting: 23 intensive neurorehabilitation units.Subjects: 264 patients with DoC in the post-acute phase: VS/UWS = 141, and MCS = 123 due to vascular (n = 125), traumatic (n = 83) or anoxic (n = 56) brain injury.Main Measures: Coma Recovery Scale-Revised, and Disability Rating Scale (DRS); presence of medical devices (e.g., for eating or breathing); occurrence and severity of medical complications.Results: patients in DoC, and particularly those in VS/UWS, showed severe overall clinical complexity. Anoxic patients had higher overall clinical complexity, lower level of responsiveness/consciousness, higher functional disability, and higher needs of medical devices. Vascular patients had worse premorbid clinical comorbidities. The two etiologies showed a comparable rate of MC, higher than that observed in traumatic etiology.Conclusion: overall clinical complexity is significantly higher in VS/UWS than in MCS, and in non-traumatic vs. traumatic etiology. These findings could explain the worse clinical evolution reported in anoxic and vascular etiologies and in VS/UWS patients and contribute to plan patient-tailored care and rehabilitation programmes.

Multi-center observational study on occurrence and related clinical factors of neurogenic heterotopic ossification in patients with disorders of consciousness.

Aims: to assess occurrence and clinical correlates of neurogenic heterotopic ossifications (NHO) in patients with prolonged disorder of consciousness (DoC).Design: multi-center cross-sectional observational study.Setting: 23 intensive neurorehabilitation units.Subjects: 287 patients with prolonged disorder of consciousness (DoC; 150 in vegetative state, VS, and 128 in minimally conscious state, MCS) of different etiology (vascular = 125, traumatic = 83, anoxic = 56, others = 14).Main Measures: clinical evidence of NHO confirmed by standard radiological and/or sonographic evaluation; Coma Recovery Scale-Revised; Disability Rating Scale (DRS); Early Rehabilitation Barthel Index; presence of ventilator support, spasticity, bone fractures and paroxysmal sympathetic hyperactivity.Results: 31 patients (11.2%) presented NHO. Univariate analyses showed that NHO was associated with VS diagnosis, traumatic etiology, high DRS category and total score, and high occurrence of limb spasticity and bone fractures. A cluster-corrected binary logistic regression model (excluding spasticity available in a subset of patients) showed that only lower DRS total score and presence of bone fractures were independently associated with NHO.Conclusions: NHO are relatively frequent in patients with DoC, and are independently associated with functional disability, bone fractures and spasticity. These findings contribute to identifying patients with DoC prone to develop NHO and requiring special interventions to improve functional recovery.

Multimodal X-ray imaging of grain-level properties and performance in a polycrystalline solar cell.

The factors limiting the performance of alternative polycrystalline solar cells as compared with their single-crystal counterparts are not fully understood, but are thought to originate from structural and chemical heterogeneities at various length scales. Here, it is demonstrated that multimodal focused nanobeam X-ray microscopy can be used to reveal multiple aspects of the problem in a single measurement by mapping chemical makeup, lattice structure and charge collection efficiency simultaneously in a working solar cell. This approach was applied to micrometre-sized individual grains in a Cu(In,Ga)Se2 polycrystalline film packaged in a working device. It was found that, near grain boundaries, collection efficiency is increased, and that in these regions the lattice parameter of the material is expanded. These observations are discussed in terms of possible physical models and future experiments.

Biallelic mutations in mitochondrial tryptophanyl-tRNA synthetase cause Levodopa-responsive infantile-onset Parkinsonism.

Mitochondrial aminoacyl-tRNA synthetases (mtARSs) are essential, ubiquitously expressed enzymes that covalently attach amino acids to their corresponding tRNA molecules during translation of mitochondrial genes. Deleterious variants in the mtARS genes cause a diverse array of phenotypes, many of which involve the nervous system. Moreover, distinct mutations in mtARSs often cause different clinical manifestations. Recently, the gene encoding mitochondrial tryptophanyl tRNA synthetase (WARS2) was reported to cause 2 different neurological phenotypes, a form of autosomal recessive intellectual disability and a syndrome of severe infantile-onset leukoencephalopathy. Here, we report the case of a 17-year-old boy with compound heterozygous mutations in WARS2 (p.Trp13Gly, p.Ser228Trp) who presented with infantile-onset, Levodopa-responsive Parkinsonism at the age of 2 years. Analysis of patient-derived dermal fibroblasts revealed decreased steady-state WARS2 protein and normal OXPHOS content. Muscle mitochondrial studies suggested mitochondrial proliferation without obvious respiratory chain deficiencies at the age of 9 years. This case expands the phenotypic spectrum of WARS2 deficiency and emphasizes the importance of mitochondrial protein synthesis in the pathogenesis of Parkinsonism.

Use of robotic colonoscopy in patients with previous incomplete colonoscopy.

OBJECTIVE: Conventional colonoscopy (CC) is the gold standard to diagnostic and therapeutic approach to colon. However, in few cases, cecal intubation could fail due to colon anatomy, patient compliance and physician expertise. Endotics robotic colonoscopy is a novel, safe, mini-invasive modality to explore the entire colon. Our aim was to assess, in a retrospective study, Endotics ability of cecal intubation in all cases in which CC failed. PATIENTS AND METHODS: Between January 2008 and December 2012, 276 Endotics robotic colonscopy examinations were performed at the Gastroenterology and Metabolic Diseases Unit of Pisa University Hospital, Pisa, Italy, in a series of consecutive patients who had undergone CC and failed cecal intubation. RESULTS: We assessed the cecal intubation rate in 102 patients addressed to Endotics after previous incomplete CC. Overall, endotics system was successful in 93.1% of the incomplete conventional colonoscopy cases (95% performance). CONCLUSIONS: Whenever the intended exploration of the entire colon with CC failed, the endotics robotic endoscopy represented a useful tool as it helped examine the entire colon in almost all cases.

An enhanced surveillance program for adult T-cell leukemia in central Brooklyn.

The Brooklyn Adult T-cell Leukemia/Lymphoma (ATL) study was developed to estimate the incidence of the human T-cell lymphotropic virus type I (HTLV-I)-associated ATL in the Crown Heights/Bedford Stuyvesant community. This central Brooklyn black community is an area which has already been shown in earlier reports to be endemic for HTLV-I-associated ATL. Surveillance has been conducted at seven area hospitals that serve this community, with surveillance already completed at five hospitals. Potential study subjects who are 20 years or older are identified by the review of admission records, discharge summaries, pathology and clinical chemistry reports, or physician referrals. Diagnoses of leukemia or lymphoma, or the presence of leukocytosis or hypercalcemia are used as criteria to identify the subjects. Participating subjects give a sample of blood for the determination of HTLV-I infection by serologic tests. At the time of enrollment, subjects provide demographic information including age, sex and birthplace. After one year of surveillance at five hospitals (39.5% of inpatient beds in the catchment), we have identified 12 cases of HTLV-I-associated ATL. The mean age of the ATL patients was 50 years, with patients being predominantly female (83.3%) and often Caribbean immigrants (83.3%). Interestingly, 42% of our cases were identified solely by findings of hypercalcemia from clinical chemistry reports. The remaining ATL cases were identified by physician referral. This enhanced surveillance program that uses both clinical and laboratory criteria for ATL case ascertainment can serve as a prototype for similar surveillance in other areas endemic for HTLV-I-associated ATL--an important effort because of the strong potential for disease prevention.

Pulmonary hypertension in primary Sjögren's syndrome: report of a case and review of the literature.

A 61-year-old female with a history of vaginal dryness, Raynaud's phenomenon, xerostomia and xerophthalmia presented with exertional dyspnoea and weakness. Laboratory and instrumental examinations enabled us to make the diagnosis of primary Sjögren's syndrome, while cardiologic and imaging investigations evidenced isolated pulmonary hypertension and ruled out pulmonary fibrosis. Oral anticoagulant and furosemide therapy induced a partial improvement of exertional dyspnoea and weakness.

Development of an in situ temperature stage for synchrotron X-ray spectromicroscopy.

In situ characterization of micro- and nanoscale defects in polycrystalline thin-film materials is required to elucidate the physics governing defect formation and evolution during photovoltaic device fabrication and operation. X-ray fluorescence spectromicroscopy is particularly well-suited to study defects in compound semiconductors, as it has a large information depth appropriate to study thick and complex materials, is sensitive to trace amounts of atomic species, and provides quantitative elemental information, non-destructively. Current in situ methods using this technique typically require extensive sample preparation. In this work, we design and build an in situ temperature stage to study defect kinetics in thin-film solar cells under actual processing conditions, requiring minimal sample preparation. Careful selection of construction materials also enables controlled non-oxidizing atmospheres inside the sample chamber such as H2Se and H2S. Temperature ramp rates of up to 300 °C/min are achieved, with a maximum sample temperature of 600 °C. As a case study, we use the stage for synchrotron X-ray fluorescence spectromicroscopy of CuIn(x)Ga(1-x)Se2 (CIGS) thin-films and demonstrate predictable sample thermal drift for temperatures 25-400 °C, allowing features on the order of the resolution of the measurement technique (125 nm) to be tracked while heating. The stage enables previously unattainable in situ studies of nanoscale defect kinetics under industrially relevant processing conditions, allowing a deeper understanding of the relationship between material processing parameters, materials properties, and device performance.

Influence of mucin type on polymer-mucin rheological interactions.

There are numerous in vitro methods with which to investigate the mucoadhesive properties of polymers. One recent method is based on the measurement of rheological interactions between polymer and mucin, which implies the use of mucins isolated from the mucous tissue. The extraction and purification of glycoprotein fraction, which is responsible for rheological interaction, can modify the native structure of mucin or spoil it with exogenous substances. Therefore the particulars of the mucin employed (origin, purification grade, the effect of further treatments such as freezing or freeze-drying) are likely to be critical for the interaction. The aim of this work was to compare some commercial mucins of differing origin and grade of purification for their rheological interaction with well-known mucoadhesive polymers (polyacrylic acid and sodium carboxymethylcellulose). For polyacrylic acid, which is sensitive to ions, we found rheological interaction to be strongly influenced by mucin type. The removal of ions, with dialysis, improved the interaction. For sodium carboxymethylcellulose, which is less sensitive to ions, rheological interaction proved to be less dependent on mucin type and improved upon glycoprotein solubilization.

On the employment of lambda carrageenan in a matrix system. III. Optimization of a lambda carrageenan-HPMC hydrophilic matrix.

The lambda carrageenan/HPMC ratio in matrix tablets has been optimized in order to obtain pH-independent release profiles of chlorpheniramine maleate, a freely soluble drug. Release profiles in acidic (pH1.2) and neutral (pH 6.8) media were fitted according to the Weibull and the power law models. Model independent parameters(t50% and the percentage of drug released after 2 h) were also calculated. The Weibull parameters were found suitable to describe the dependence of the release profiles on matrix composition. Preparation and testing of the optimized formulation showed linear and pH-independent release profiles lasting about 24 h, in good accordance with the values predicted by the optimization procedure.

Ischemic encephalopathy in ANA-negative systemic lupus erythematosus.

A woman with a nine-year history of Raynaud's phenomenon developed photodermatitis and a sudden neurological syndrome characterized by transient focal disorders accompanied by wide and persistent cerebral lesions demonstrated by CT, NMR and SPECT imaging. A careful evaluation of the clinical manifestations of neurological SLE along with the detection of anti-Ro/SSA antibodies prompted us to reconsider the diagnosis of SLE. Moreover, the discrepancy observed between the poor neurological picture and the widespread encephalic alterations shown by CT, NMR and SPECT imaging suggests that it may be useful to conduct these investigations in patients affected by SLE with modest neurological signs and symptoms. A further interesting aspect of this case is represented by the differential diagnosis with two other diseases, such as Sneddon's syndrome and multiple sclerosis, which are characterized by the presence of certain clinical and instrumental findings also observed in neurological SLE.

High-dose interferon plus ribavirin in chronic hepatitis C not responding to recombinant alpha-interferon.

BACKGROUND: Recently, the combination treatment of recombinant alpha-interferon plus ribavirin has been proposed for chronic hepatitis C patients unresponsive to previous therapy with recombinant alpha-interferon alone. AIM: To determine the effectiveness of the combination therapy for the re-treatment of chronic hepatitis C patients unresponsive to previous interferon therapy. Immediate and long-term follow-up data are reported. PATIENTS AND METHODS: A series of 100 patients with chronic hepatitis C not responding to recombinant alpha-interferon 3 MU tiw, were randomly assigned to two groups of 50 patients each: Group A, treated with recombinant alpha-interferon therapy for an additional six months but at a double dosage (6 MU tiw) in association with ribavirin. Group B, same treatment as group A but without ribavirin. All patients responsive to therapy were then followed-up for at least 12 months. At the end of the treatment and at the end of the follow-up period, we distinguished between complete responses (return to normal of alanine aminotransferase with undetectable serum HCV-RNA] and biochemical responses (return to normal of alanine aminotransferase still with detectable viraemia). RESULTS: Side-effects were observed only in patients treated with recombinant alpha-interferon plus ribavirin: 12% discontinued the therapy due to haemolytic anaemia. In group A, the percentages of end-of-treatment complete response, end-of-treatment biochemical response, sustained complete response, and sustained biochemical response, were 38%, 20%, 8%, and 14%, respectively, whilst in group B, these percentages were 12%, 16%, 6%, and 16%, respectively. CONCLUSION: The results indicate that in patients with chronic hepatitis C unresponsive to previous recombinant alpha-interferon therapy, re-treatment with higher recombinant alpha-interferon doses, either alone or in combination with ribavirin, lead to mild long-term benefit. However, the satisfactory end of treatment complete response in group A suggests that a significant percentage of patients are sensitive to the combination therapy; and that a more aggressive therapeutic protocol in this selected subset of patients could result in a larger number of long-lasting responses leading, in turn, to a more favourable cost-effect ratio.

Long-term maintenance treatment in ulcerative colitis: a 10-year follow-up.

BACKGROUND: With the extensive use of mesalamine, the natural history of ulcerative colitis is probably changed. AIM: To evaluate the relapse rate and the duration of remission in patients with ulcerative colitis on maintenance treatment with mesalamine. PATIENTS AND METHODS: Enrolled in the study were 95 patients divided into 4 groups according to macroscopic location of the disease and treated with the same therapy starting from the date of enrolment. Patients in all 4 groups were followed-up until relapse occurred. The disease activity was evaluated by the Clinical Activity Index and Endoscopic Index. Patients suitable for recruitment showed a Clinical Activity Index and Endoscopic Index lower than 6 and 4, respectively. The patients with ulcerative pancolitis or left-sided colitis were treated with 1.6 g/day while the cases with proctosigmoiditis or proctitis were treated with 5-acetylsalicylic acid enemas 4 g/day Each patient was evaluated with clinical and endoscopic assessment at a 6-month interval. Relapse was defined as an increase in Clinical Activity Index and Endoscopic Index, of more than 6 and 4, respectively. RESULTS: Five patients dropped-out. All enrolled patients showed a clinical and/or endoscopic relapse within 10 years, the majority 2 or 3 years after diagnosis: pancolitis and left-sided colitis within 2-3 years and patients with distal colitis within 9-10 years. CONCLUSIONS: A relapse was observed in most cases within 3 years, and in all recruited patients within a space of ten years. The extent of the disease in the colon is an important prognostic factor, as patients with distal colitis showed a lesser tendency to relapse.

The sterols of Cucurbita moschata ("calabacita") seed oil.

From the sterol fraction of seed oil from commercial Cucurbita moschata Dutch ("calabacita") delta 5 and delta 7 sterols having saturated and unsaturated side chain were isolated by chromatographic procedures and characterized by spectroscopic (1H and 13C-nuclear magnetic resonance, mass spectrometry) methods. The main components were identified as 24S-ethyl 5 alpha-cholesta-7,22E-dien-3 beta-ol (alpha-spinasterol); 24S-ethyl 5 alpha-cholesta-7,22E,25-trien-3 beta-ol (25-dehydrochondrillasterol); 24S-ethyl 5 alpha-cholesta-7,25-dien-3 beta-ol; 24R-ethyl-cholesta-7-en-3 beta-ol (delta 7-stigmastenol) and 24-ethyl-cholesta-7, 24(28)-dien-3 beta-ol (delta 7,24(28)-stigmastadienol).

Suicidal poisoning with barium chloride.

A 49-year-old male pharmacist suffering from depression phoned the emergency services telling of how he had ingested barium chloride. He was found semicomatose in bed and resuscitation attempts were to no avail and he died at the scene. A white plastic container labelled "Barium chloride... Poison", and a book with a writing on a blank page... "give sulphate... SO(4)" were found. At autopsy, 1l of whitish-yellow fluid was found in the stomach. Autopsy barium levels were: blood 9.9mg/l; bile 8.8mg/l; urine 6.3mg/l; gastric 10.0g/l. Cause of death was given as cardiorespiratory arrest due to barium chloride poisoning. The issue of barium toxicity in a variety of itatrogenic and non itatrogenic situation is discussed together with the two only other cases of suicidal barium ingestion, and the feasibility of early intervention at the scene by an emergency team.

[Fungal endophytes in Juncus imbricatus var chamissonis: identification of colonization patterns.]. / Endofitos fúngicos en Juncus imbricatus var chamissonis: identificación de los patrones de colonización.

Colonization patterns corresponding to individual endophytic species were observed in asymptomatic leaves and culms of Juncus imbricatus var chamissonis, a perennial plant. The presence of the fungi within the host was demonstrated by light microscopy after the cleaning and staining of tissues. The main endophytic species, Pleospora aff togwotiensis, was found colonizing the substomatal chamber and growing intercellularly between mesophyll cells. In a second colonization pattern, an unknown fungus was restricted to a single host epidermal cell, showing similar characteristics to other fungal taxa observed on Juncus effusus var pacificus, Pseudotsuga menziessii and Fagus sylvatica. A third colonization pattern, where the mycelium is confined to the substomatal chamber, was also described.

Sustained remission and viraemia in chronic hepatitis C treated with recombinant alpha-interferon (rIFN-alpha).

In this retrospective trial we report the immediate and long-term effects of rIFN-alpha therapy on serum aminotransferases, especially on their behaviour in relation to the disappearance of serum HCV-RNA at the end of the treatment and one year later. Eighty-eight subjects were eligible in our study. The diagnosis of hepatitis was based on clinical, serological and histological data in all patients. They showed ALT and AST levels at least twice the upper maximum normal value and detectable serum HCV-RNA before the study. These patients were treated with rIFN-alpha 3MU, 3 times a week, in 54 cases for 6 months and in 34 for 1 year. Patients were examined at monthly intervals. Serum HCV-RNA was assessed before and at the end of the treatment and every six months during the follow-up. A complete response was defined exclusively as a normalization of aminotransferases and disappearance of serum HCV-RNA. The two groups were homogeneous. During the treatment drop-outs were 5 (5.7%), and 7 patients (7.9%) stopped the therapy for side-effects. The treatment induced a complete response in 13 (25.4%) of 51 patients treated for 6 months, and in 8 (32%) of 25 cases treated for 12 months. The patients with normalization of aminotransferase levels but with still detectable HCV-RNA in serum were 20 (39.2%) of 51 treated for 6 months and 13 (41.9%) of 31 treated for 12 months. The cases with normalization of aminotransferases were followed up for one year after IFN withdrawal. Serum liver function tests and HCV-RNA were performed every 6 months in these patients. One year after IFN withdrawal the numbers with persistent normalization of liver enzymes and absence of serum HCV/RNA were 9 (69.2%) of 13 cases with complete response after a 6-month course, and 5 (62.5%) of 8 subjects with complete response after a 12-month course. The subjects with continuous normalization or liver enzymes but persistence of serum HCV-RNA at the end of the trial were 3 (15.7%) of 19 patients with normalization of liver enzymes and still detectable HCV-RNA after a 6-month course, and 2 (15.3%) of 13 cases with normalization of liver enzymes and still detectable HCV-RNA after a 12-month course. Overall at the end of our study the patients with normal aminotransferases were 19 (21.5%) of 88 cases studied. 14 of them (73.6%) being from the subjects with disappearance of serum HCV-RNA just after IFN treatment.

Evaluation of clinical patterns in ulcerative colitis: a long-term follow-up.

The aim of this prospective research was to compare, in a seven-year follow-up, the clinical outcome of ulcerative pancolitis with that of non-progressive ulcerative colitis. The activity of the disease was evaluated by a Clinical Activity Index and an Endoscopic Index. Of 112 cases of ulcerative colitis observed, 95 showed no change in extent and were studied as examples of non-progressive UC, and in this group the extension of the disease was: pancolitis in 19%, left-sided colitis in 39%, proctosigmoiditis in 17% and proctitis in 25%. A colectomy had to be performed in 5%. None of the enrolled cases developed a cancer during the follow-up. The patients with ulcerative pancolitis or left-sided colitis were treated with 5-ASA 1.6 g/day in a delayed-release formulation, while the cases with proctosigmoiditis or proctitis were treated with 5-ASA enemas 4 g/day. The cases with more than one relapse/year were 39%. The proportion of patients with only one relapse/year was 53%. The patients with steady remission for all the seven years of the trial were only 8%, but with a statistically significant difference between the groups with initial diagnosis of proctosigmoiditis or proctitis and the group with initial diagnosis of pancolitis or left-sided colitis (12% versus 5%). Among the cases with continuous remission, 37% showed colonic alterations, with an endoscopic score higher than 4 but a clinical score less than 6. Side-effects were observed in 6% patients but without treatment withdrawal. Non-progressive ulcerative colitis throughout the colon has a relatively good prognosis which seems to be independent of the location of the disease, even if we have found a statistically significant higher percentage of cases with steady remission among the patients with more distal disease.

Eosinophilic pleural effusion with Charcot-Leyden crystals.

A 17-year-old female presented with an eosinophilic pleural effusion containing many Charcot-Leyden crystals. She was found to have a benign cystic teratoma of the anterior mediastinum.

[Recent findings in the pathogenesis of bronchial asthma]. / Recenti acquisizioni sulla patogenesi dell'asma bronchiale.

The latest discoveries about the pathogenesis of asthma are reported with emphasis on new data concerning the discovery of factors capable of controlling the production of IgE antibodies. The mechanisms implicated in early and late phase reactions are then discussed. In addition, the relationships between neuropeptides and chronic inflammation are described. Finally, the role of active substances produced by the bronchial epithelium on the induction and maintenance of bronchial inflammation is reviewed.