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Background: Confirmatory data on long-term effectiveness and safety of ixekizumb in psoriatic patients from real-world studies are needed. Objectives: The primary aim was to evaluate the 3-year drug survival of ixekizumab in the treatment of patients with moderate-to-severe plaque psoriasis, in a multicenter real-world setting. The secondary aim was to assess the influence of predictive factors on the drug survival of ixekizumab. Methods: A retrospective analysis was performed on a cohort of patients with chronic plaque psoriasis, who received at least one dose of ixekizumab before December 2018. The drug survival analysis was performed, descriptively analyzed using Kaplan-Meier survival curves. Multivariable Cox regression analyses were carried out including variables considered of clinical importance. Results: A total of 306 patients was enrolled. The overall drug survival at 12, 24 and 36 months of treatment with ixekizumab was 92.11%, 83.85% and 80.19%, respectively. A higher probability (HR 2.34) of drug withdrawal was found among patients who had already received an anti-IL-17 agent compared with bio-naive patients (p 0.017). Conclusions: We found that ixekizumab is a biological agent characterized by a long term effectiveness, not influenced by several clinical factors and associated with a good safety profile.

Bullous pemphigoid is the most common autoimmune bullous dermatosis. In recent years several studies have tried to identify the main factors of the disease related with an increased risk of death. The aim of this multicenter Italian study was to assess the risk score of death considering epidemiologic, clinical, immunological, and therapeutic factors in a cohort of patients affected by bullous pemphigoid and try to identify the cumulative survival up to 120 months.We retrospectively reviewed the medical records of patients with bullous pemphigoid who were diagnosed between 2005 and 2020 in the 12 Italian centers. Data collected included sex, age at the time of diagnosis, laboratory findings, severity of disease, time at death/censoring, treatment, and multimorbidity.A total of 572 patients were included in the study. The crude mortality rate was 20.6%, with an incidence mortality rate of 5.9 × 100 person/year. The mortality rate at 1, 3, 5, and 10 years was 3.2%, 18.2%, 27.4% and 51.9%, respectively. Multivariate model results showed that the risk of death was significantly higher in patients older than 78 years, in presence of multimorbidity, anti-BP180 autoantibodies72 U/mL, or anti-BP230 3 U/mL at diagnosis. The variables jointly included provided an accuracy (Harrel's Index) of 77% for predicting mortality.This study represents the first nationwide Italian study to have retrospectively investigated the mortality rates and prognostic factors in patients with bullous pemphigoid. A novel finding emerged in our study is that a risk prediction rule based on simple risk factors (age, multimorbidity, steroid-sparing drugs, prednisone use, and disease severity) jointly considered with two biomarkers routinely measured in clinical practice (anti-BP230 and anti-BP180 autoantibodies) provided about 80% accuracy for predicting mortality in large series of patients with this disease.

Most patients with psoriasis present with localized mild-to-moderate disease. In this case, the application of topical treatments in the first-line setting is recommended in most cases. Among different topical options, the fixed-dose combination of betamethasone dipropionate (BD) and vitamin D analogue (Cal) aerosol foam (Enstilar®, Leo Pharma) is approved as first-line topical therapy for the treatment of psoriasis in USA and the EU, due to its high efficacy and its favorable administration scheme. The PSO-LONG was the first trial to report on the long-term efficacy and safety of the Cal/DB foam treatment for the proactive management of psoriasis and now, the indications of Cal/BD foam included its use in the psoriasis maintenance treatment. However, the precise role of this treatment and the potential therapeutic schemes in the long-term management of psoriasis need further clarification. This Position Paper, authored by a group of Italian Expert Dermatologists, critically discusses the long-term management of psoriasis with Cal/BD foam in clinical practice. In particular, the biological rationale in the proactive treatment with Cal/BD foam and current evidence regarding this therapeutic approach are presented, along with its application also in patients with moderate-to-severe disease, difficult-to-treat lesions, or within combination regimens. In addition, strategies to improve adherence to long-term treatment of psoriasis are discussed,.

Background Anti‐tumour necrosis factor (TNF) and anti‐interleukin (IL)‐12/23 biologics revolutionized plaque psoriasis treatment by enabling ≥75% improvement in the Psoriasis Area and Severity Index (PASI 75) in clinical trials. Modern biologics are now reported to achieve PASI 100 (complete skin clearance) in clinical trials. However, real‐world evidence of skin clearance rates with biologics is limited. PSO‐BIO‐REAL was conducted to understand the real‐world burden of plaque psoriasis. Objective The primary objective of this observational study was to estimate the proportion of patients who achieved complete skin clearance at 6 months. Secondary objectives included maintenance of response and evaluation of complete skin clearance at 12 months. Methods PSO‐BIO‐REAL was a multinational, prospective, real‐world, non‐interventional study of skin clearance and patient‐reported outcomes (PROs) with biologics. A total of 846 patients from the United States (32%), France (28%), Italy (22%), the United Kingdom (11%) and Germany (8%) were enrolled and followed for one year. Eligible patients were aged ≥18 years with moderate‐to‐severe plaque psoriasis who had initiated a biologic for plaque psoriasis. Patients could be biologic‐naïve or switching biologics (biologic‐experienced). Assessments were made at baseline and at months 6 and 12. Results At 6 and 12 months, 23% and 26% of patients achieved complete skin clearance, respectively. Prior to study entry, 60% were biologic‐naïve. The proportion of patients achieving complete skin clearance was lower among biologic‐experienced patients (20% at both months 6 and 12) compared with biologic‐naïve patients (25% at month 6, 30% at month 12). The rate of complete skin clearance decreased as the number of prior biologics and baseline comorbidities increased. Conclusion Only one in four patients achieved complete skin clearance after 6 months of treatment with biologics. The study indicates there still is an unmet need for more efficacious biologics for patients with psoriasis.

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Background: Real-life data often highlight the side effects of certain drugs not previously reported in randomized controlled trials (RCTs).Objective: To describe cutaneous inflammatory eruptions i...

Background Bariatric surgery (BS) represents the most effective treatment for morbid obesity and its related complications, potentially ameliorating chronic comorbid inflammatory skin conditions, such as psoriasis and hidradenitis suppurativa (HS). Weight-loss interventions are strongly encouraged in patients with HS, but the resulting effect on the course of the disease has been poorly reported. Aim To describe the effect of BS-associated weight-loss on the course of HS. Methods This was a retrospective, descriptive study of a hospital-based patient cohort with HS in order to investigate the relationship between exposure to a BS procedure and the HS disease course. Clinical characteristics and BS-related outcomes were retrospectively analysed by chart review for identified cases. Laboratory parameters for selected micronutrients (levels of vitamin A, D and B12, plus zinc and iron) were re-evaluated at a follow-up visit in each post-BS case. Typical patients with HS from the general cohort served as controls for the comparison of vitamin D and zinc serum levels. Results Of 178 patients with HS, 12 patients with incident HS who had undergone a BS procedure were identified. A subset of patients (n = 10) developed initial signs and symptoms of cutaneous suppuration after experiencing weight loss related to malabsorptive bariatric procedures. Post-BS patients with HS presented multiple micronutritional deficiencies and insufficient responses to standard, first-line antibiotic treatments. Of the micronutrients we selected for analysis, zinc was found to be at significantly lower serum levels in post-BS patients with HS compared with typical patients with HS. Conclusions Post-BS HS may represent a new patient subset, requiring customized clinical management.

Background Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with psoriasis (PsO). Early diagnosis and prompt therapeutic intervention are crucial for limiting PsA progression and prevention of disability. Dermatologists are in a privileged position to detect early PsA. The management of patients with PsA in the dermatology setting is widely variable. Objective To provide practical recommendations for the management of patients with PsA in the dermatology setting including early diagnosis and treatment. Methods A consensus document was written by an expert panel composed by dermatologists (n = 12) and rheumatologists (n = 6). Eleven highly relevant questions were selected and elaborated with answers/statements based on a narrative literature review. The resulting document was discussed in a face-to-face meeting adopting a nominal group technique to reach consensus (i.e. 100% agreement) using the Delphi method. Results A consensus was achieved in defining the following: the clinical characteristics differentiating inflammatory and non-inflammatory signs and symptoms of joint disease; the most important differential diagnoses of PsA in clinical practice; the most useful screening questionnaires, serum laboratory tests and imaging techniques for the detection of early PsA; the criteria for dermatologist to refer patients with PsO to rheumatologist; the criteria for the diagnosis of PsA; the selection of the indices that the dermatologist could use for measuring the activity and severity of PsA in clinical practice; when systemic steroids and/or intra-articular steroid injections are indicated in the treatment of PsA. Finally, systemic treatments including synthetic and biologic disease-modifying antirheumatic drugs to be considered for the treatment of PsA have been reported. Conclusions The implementations of these practical recommendations could be very helpful for the management of patients with PsA in the dermatology setting including early diagnosis and treatment.

Two-component Pt

Background and Aims Varietal thiols, important odorous molecules in wine, have been identified in Vitis vinifera L. grapes as S-cysteinylated and S-glutathionylated odourless precursors. The aim of this paper is to investigate the presence of these precursor compounds during ripening of two Italian white grape cultivars, Grechetto and Malvasia del Lazio, in comparison with the well-characterised, reference cultivar Sauvignon Blanc. Methods and Results Grapes were sampled and sorted according to density in order to obtain homogeneous samples at the TSS concentration of 16, 19 and 22°Brix, as a synthetic index of ripening stage. After sorting and processing the grapes, the concentration of thiol precursors contained in each sample of juice was determined by liquid chromatography-quadrupole MS. For the first time, S-3-(4-sulfanyl-4-methylpentan-2-ol)-glutathione was identified and quantified in the three cultivars as a glutathione-conjugated precursor. Both S-cysteinylated and S-glutathionylated precursors were ubiquitous in the three cultivars, although their concentration varied significantly. Conclusion Thiol precursors increased with TSS during ripening in Sauvignon Blanc and Grechetto, while no variation of these odourless compounds was observed in Malvasia del Lazio, which also had a lower concentration of these precursors. Significance of the Study This work contributes to defining the significance of these precursors to the varietal attributes of the resulting wines, as well as indicating the optimal harvest time of grapes for maximal expression of thiol varietal attributes in wine.

Summary Background Chronic plaque psoriasis is frequently associated with metabolic disorders including obesity. Antitumour necrosis factor α treatments can induce body-weight increase in patients with psoriasis. Information on the effect of ustekinumab on body weight is not available. Objectives To investigate whether therapy with ustekinumab is associated with changes in body mass index (BMI) in patients with chronic plaque psoriasis. Methods A prospective, multicentre study comparing the changes in BMI in two closed cohorts of patients with psoriasis during 7-month treatment with ustekinumab (n = 79) or infliximab (n = 83). Results Patients treated for 7 months with infliximab showed a significant (P 2%, compared with only 11% of those receiving ustekinumab (P = 0·01). In the multivariate analysis, all other clinical parameters predicted the BMI increase, except for the use of infliximab. At month 7, 96% of patients treated with infliximab and 82% of patients treated with ustekinumab achieved at least a 50% improvement from their baseline psoriasis area and severity index (PASI 50), and 69% of the infliximab group compared with 58% of the ustekinumab group achieved at least PASI 75. There was no difference in the proportion of PASI 50 and PASI 75 responders between the two groups. Conclusions In contrast to infliximab, ustekinumab does not increase BMI in patients with chronic plaque psoriasis. This difference could be taken into account in the selection of biologics when treating patients with psoriasis.

The influence of halogen atom substitution (Br and I), in different amounts and positions in an aza-BODIPY skeleton, on the photophysical properties of some aza-BODIPY derivatives has been investigated by using density functional theory and its time-dependent extension. The heavy atom effect on excitation energies, singlet–triplet energy gaps and spin–orbit matrix elements has been considered. The maximum absorption within the therapeutic window has been confirmed for all the aza-BODIPY derivatives. The feasible intersystem spin crossing pathways for the population of the lowest triplet state, that will depend on the values of the spin–orbit matrix elements, the energy gap as well as the orbital composition of the involved states have been found to most likely involve the S1 and T1 or T2 states. The outcomes of computations support the potential therapeutic use of these compounds as photosensitizers in photodynamic therapy.

Etanercept is a fusion protein of soluble TNF receptor type II with human IgG Fc fragment, whose use was approved for psoriasis by the FDA and by the EMEA. It neutralizes the proinflammatory effects of TNF-α, a cytokine with a pivotal role in the pathogenesis of psoriasis, preventing binding to its receptors. The aim of our study was to review the emerging evidence of the therapeutic value of etanercept in the treatment of psoriasis. We found that since its approval, several randomised clinical trials have shown its efficacy in the short and long-term, both in a continuous and interrupted course of therapy. Data deriving from these studies have also suggested an acceptable safety profile, as found also in studies conducted on its use in other autoimmune diseases. Etanercept also seems to be efficacious and safe when administered in a combined treatment with other traditional medications and after switching from another biological drug. Moreover, despite its high costs it does seem to be a cost-effective treatment.

Summary Background Systemic sclerosis (SSc) and morphoea are connective tissue diseases characterized by fibrosis of the skin. Although to date their pathogenesis has not been clearly defined, it is thought that autoimmunity may play a role in the development of the skin lesions observed in both these diseases. As regulatory T cells (Tregs) play a key role in the modulation of immune responses, it has recently been suggested that Treg impairment may lead to the development of autoimmune diseases. Objectives To investigate the presence of Tregs and their immunomodulatory cytokines, transforming growth factor (TGF)-β and interleukin (IL)-10, in patients with SSc and morphoea. Patients/methods Fifteen patients with SSc and 15 with morphoea were enrolled. Immunohistochemistry was applied to identify FoxP3+ (forkhead/winged helix transcription factor) Tregs, TGF-β+ cells and IL-10+ cells in the skin, cytofluorometry to detect CD4+CD25+FoxP3+ Tregs in the blood, and enzyme-linked immunosorbent assays to analyse TGF-β and IL-10 serum levels. Results Fewer FoxP3+ Tregs and TGF-β+ and IL-10+ cells were found in the skin of patients with scleroderma than in controls. Similarly, there were reduced TGF-β and IL-10 serum levels and fewer circulating CD4+CD25brightFoxP3+ cells in patients with SSc or morphoea, than in controls. Conclusions The quantitative reduction of Tregs, together with that of TGF-β and IL-10 serum levels, may be responsible for the loss of tolerance observed in both SSc and morphoea.

Several studies have demonstrated that ceramides play an essential role in both the barrier and water-holding functions of healthy stratum corneum, suggesting that the dysfunction of the stratum corneum associated with ageing as well that observed in patients with several skin diseases could result from a ceramide deficiency. In a previous study our group reported a significant increase in skin ceramide levels in healthy subjects after treatment in vivo with a cream containing a preparation of Streptococcus thermophilus. The presence of high levels of neutral sphingomyelinase activity in this organism was responsible for the observed increase of stratum corneum ceramide levels, thus leading to an improvement in barrier function and maintenance of stratum corneum flexibility. The aim of the present work is to investigate the effects of the topical treatment of a Streptococcus thermophilus-containing cream on ceramide levels of stratum corneum of healthy elderly women. The ceramide levels, transepidermal water loss and capacitance were evaluated on stratum corneum sheets from the forearms of 20 healthy female subjects treated with a base cream or the same cream containing a sonicated preparation of the lactic acid bacterium Streptococcus thermophilus. A 2-week topical application of a sonicated Streptococcus thermophilus preparation led to significant and relevant increase of stratum corneum ceramide levels. Moreover, the hydration values of the treated forearm of each subject was significantly higher than control sites. These results suggest that the experimental cream was able to improve the lipid barrier and to increase a resistance against ageing-associated xerosis.

Summary Background Erythema multiforme (EM) and Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are caused by a dysregulation of cellular immunity. Objectives To evaluate further the potential role of certain cytokines and chemokine receptors in cutaneous lesions of patients affected by EM and SJS/TEN and to establish whether such diseases are polarized preferentially towards a T-helper (Th) 1 or Th2 pattern. Methods Biopsy specimens from eight patients with EM, six with SJS/TEN and three healthy controls were stained for immunohistochemical examination using the alkaline phosphatase–antialkaline phosphatase method. The monoclonal antibodies used included those to tumour necrosis factor (TNF)-a, interferon (IFN)-c, interleukin (IL)-2, IL-5, IL-13, receptor 3 for C-C chemokines (CCR3), receptor 3 for C-x-C chemokines (CXCR3) and CXCR4. Results The SJS/TEN specimens showed significantly higher expression of all the cytokines and chemokine receptors (except CXCR3) tested than the EM specimens. Both lesional series showed significantly higher expression of all the receptors tested than the healthy control specimens, with the sole exception of a lower expression of CCR3 in EM specimens. Comparison between molecules associated with a Th1 or Th2 response revealed a predominance of Th1 response in EM and no significant imbalance between Th1 and Th2 in SJS/TEN. Conclusions We have provided further evidence that TNF-a is strongly expressed in SJS/TEN lesions and therefore it may be involved in the epidermal necrosis featured in such diseases. IFN-c may play an important role both in EM and SJS/ TEN. IL-2, IL-5 and IL-13 may contribute to the cutaneous immunoinflammation in these diseases. Chemokine receptors may be involved strongly in the recruitment of inflammatory cells in lesional skin. In our cases we found a sharp polarization towards a Th1 pattern in EM, while the SJS/TEN lesions showed a mixed Th1/Th2 pattern.

Background: The incremental shuttle walking test (SWT) has recently been proposed as a more valid and reproducible alternative to the conventional 6-min walking test (6MWT) in the evaluation of exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). Objective: To compare the cardiorespiratory performance obtained during two sessions of SWT with that obtained during two sessions of 6MWT. Methods: We examined 18 patients (forced expiratory volume in 1 s: 48 ± 14%) recovering from an acute exacerbation of COPD that had required hospitalization. In the same afternoon, each patient performed two SWT and two 6MWT, with an interval of at least 30 min between each test; the sequence of the tests was randomized. Results: Mean walking distance was greater in the second SWT test than in the first SWT. The changes from baseline in systolic blood pressure, heart rate, respiratory rate, oxygen saturation and dyspnea Borg index at the end of the test were similar between the two 6MWT and the two SWT. There was a highly significant correlation between walking distances measured during SWT and during 6MWT (ρ: 0.85, p < 0.0005). Neither SWT nor 6MWT correlated with functional data of COPD. Conclusions: SWT, though being considered to be closer to a submaximal exercise test than 6MWT, does not induce a greater cardiorespiratory performance than 6MWT in patients recovering from acute exacerbation of COPD.

An approach to electrical impedance tomography (EIT) data acquisition inspired by NMR-filtered back-projection imaging with fan isochromat distribution is proposed. A current projection is generated by injecting current at a certain point of the sample and simultaneously collecting the current itself at different points on the half space opposite the point of current injection. After that, the injection is shifted to another point and collected as above and so on. A very simple algebra and software support the numerical simulations. This method is expected to be more sensitive than the traditional method based on potential measurements. A preliminary low resolution experiment is presented.

We report a 60-year-old man with familial scleroatrophic syndrome of Huriez who developed squamous cell carcinomas on the affected skin of the right palm. Immunohistochemical analysis showed a marked reduction in the number of CD1a+, Lag+ and S100+ epidermal Langerhans cells, but not of CD1b+ and factor XIIIa+ dermal dendritic cells, limited to palmoplantar skin. The Langerhans cell depletion was not associated with an abnormal skin content of mRNA for factors involved in Langerhans cell development or recruitment in the epidermis, including granulocyte/macrophage colony-stimulating factor, transforming growth factor-beta1 and macrophage inflammatory protein-3alpha. The results indicate that other as yet unknown mechanisms may account for the reduced number of Langerhans cells in the affected skin of such patients.

Pemphigus is a rare autoimmune disease characterized by flaccid blisters and erosions on skin and mucous epithelia. A critical event in its pathogenesis is production of antidesmoglein antibodies, which mediate the loss of intercellular adhesion in epithelia, leading to blister formation. Multiple environmental factors (ultraviolet radiation, trauma, drugs, infective agents) have been suggested as possible triggers of pemphigus. Occasionally, the disease has been reported to follow viral and bacterial vaccination. We describe a patient who experienced exacerbation of pemphigus shortly after administration of the influenza vaccination on two separate occasions. We review the literature, suggest possible explanations for a causal relationship, and discuss the administration of vaccination to these patients.

The progression of HIV-1 disease appears associated with an unregulated Fas-mediated apoptosis of lymphocytes that involves the activation of ICE protease and ceramide generation and antiviral therapy may not be fully effective in the absence of a relevant impact on apoptosis. Six drug-naive HIV-1-infected symptomless patients with advanced immunodeficiency were treated with combined AZT and ddl for 4 months; plasma HIV-1 RNA levels, the counts of CD4 cells, CD4 and CD8 apoptotic lymphocytes, Fas-positive cells and ICE-positive cells, and intracellular ceramide levels were measured at base-line and after 7, 45 and 120 days of treatment. There was a prompt reduction in plasma viremia and a secondary increase in CD4 counts, but the treatment had no impact on apoptotic CD4 and CD8 lymphocytes, Fas-positive cells and ICE-positive cells, and on the intracellular levels of ceramide. A discrepancy exists between the positive impact of combined AZT and ddl treatment on plasma viral load and CD4 counts and the lack of any effect on the process of lymphocyte apoptosis. We suggest to use the measurement of apoptotic lymphocytes as a surrogate marker to predict, in combination with viral load and CD4 counts, a large proportion of the clinical effect of antiviral therapy.

Polymorphonuclear cells (PMN) and monocytes/macrophages (M/M) represent the first defence line against invading microorganisms. Both phagocytic cell functions are precociously compromised in human immunodeficiency virus (HIV)-infected subjects, thus leading to infectious and neurological complications in the late stages of disease. Among intracellular pathogens, emerging bacteria such as Bartonella henselae and Rhodococcus equi can cause peculiar clinical pictures, i.e. the bacillary parenchimal angiomatosis and a classical pyogranulomatous broncopneumonia, respectively. On the other hand, overproduction of proinflammatory cytokines (CKs) and, in particular, tumor necrosis factor-alpha under HIV or lipopolysaccharide stimulation may cause neural damage in terms of demyelination and subsequent development of acquired immunodeficiency syndrome (AIDS) dementia complex. Some therapeutical attempts have been made with colony stimulating factors in order to increase the number and potentiate the function of PMN and M/M. On the other hand, the use of drugs able to reduce exaggerated release of CKs by M/M is suggested in AIDS patients in order to prevent a further aggravation of the clinical condition.

(2004). Fatal rupture of an inflammatory arterial aneurysm in a patient with Wegener's granulomatosis. Scandinavian Journal of Rheumatology: Vol. 33, No. 4, pp. 277-279.

Most studies have reported reduced carnitine levels in the tissues of patients with sepsis, probably due to increased urinary excretion. Because of the increased utilization of fatty acids and ketone bodies as sources of energy in sepsis, the carnitine deficiency can further impair the fuel metabolism and contribute to the unregulated lipid metabolism in these patients.Recently, experimental and clinical studies have shown that carnitine and its congeners are able to: (a) downmodulate the spontaneous and endotoxin (LPS)-triggered overproduction of tumor necrosis factor (TNF)-alpha; (b) ameliorate the lipid metabolism; and (c) reduce the severity of illness, accelerate recovery, and, in some cases, improve survival in experimental septic shock.Many questions concerning the ultimate molecular mechanism of action of these compounds in endotoxaemia are still unanswered. Yet, these compounds may be helpful in patients with sepsis, when associated with conventional therapy, in that they can effectively reduce TNF-alpha levels and ameliorate the host's metabolic processes.

Polymorphs (PMN) and monocytes/macrophages (Mo) play a very important role in the host defence since they participate to inflammatory processes, tissue repairing and antitumor activity. Previous studies showed that lipopolysaccharide (LPS)-activated Mo are able to upregulate PMN phagocytic ability via cell-to-cell contact mechanisms mediated by bound to Mo membrane (m) cytokines (CKs), such as Tumor Necrosis Factor (TNF)-alpha, Interleukin (IL)-1 alpha and IL-1 beta. Based on these grounds, the role of Mo m-associated IL-6 and IL-8 on the modulation of PMN activity has been evaluated. In the first step, PMN incubated with lipid A (LA)-activated Mo showed an increased phagocytosis dependent on cell-to-cell contact only. In the second step, LA-activated Mo were pretreated with antirecombinant human (Rhu) IL-6 and IL-8 monoclonal antibodies (MoAbs), respectively and, in such a way, the enhanced phagocytic activity of PMN was abrogated. In the third step, PMN incubated with LA-activated supernatants (AS) from PBMC cultures exhibited an enhanced phagocytic activity, that was abrogated when LA-AS were pretreated with anti-Rhu IL-6 and anti-Rhu IL-8 MoAbs, respectively. These data suggest that IL-6 and IL-8 associated to Mo membrane may modulate PMN activation through a cell-to-cell contact dependent pathway.

In this paper we describe a cutting plane algorithm to solve max-cut problems on complete graphs. We show that the separation problem over the cut polytope can be reduced to the separation problem ...

Summary Klippel–Trenaunay (KT) syndrome is a vascular malformation characterized by a port-wine stain, varicose veins and hypertrophy of the affected limb. Ulceration is considered an uncommon complication of KT syndrome and occurrence of skin cancer has been previously reported only in one case. We observed a case of KT syndrome in a 48-year-old woman who developed a large ulcer and a squamous cell carcinoma on the affected leg.

We present results of the photorefractive properties of a chiral smectic A liquid-crystalline phase. In our approach, the mesophase is sandwiched between two photoconducting layers. In contrast to the effect due to the dielectric anisotropy typical of nematic phases, the refractive-index modulation is due to the electroclinic effect. We measured the grating spacing and the field dependence of the gain coefficient and obtained a net two-beam coupling gain of 600 cm−1 at 35 V/μm.

Proposes an extension of the differential correction algorithm for simultaneous design of real and imaginary parts of IIR (infinite impulse response) transfer functions in minimax norm. The implementation of the proposed algorithm requires the iterative solution of a minimization problem having linear objective and quadratic constraints. The method is globally convergent and it can be proven to deliver stable IIR filters. Practical implementations of the algorithm compare very favorably with existing design tools. Actual operation is examined by means of filter design examples. >

Acetyl-L-carnitine (ALC), a drug for the treatment of ageing-related neuroendocrine dysfunctions, was orally administered--2 gm/day for 30 days--to 10 patients with active pulmonary tuberculosis (TBC). Lymphocyte-mediated antibacterial activity and serum levels of tumor necrosis factor (TNF)-alpha were evaluated before and after treatment, comparing the values with those of 10 TBC patients receiving placebo. Results show that by day 30, antibacterial activity remained unmodified or increased in ALC-treated subjects, while decreased in the placebo group. No influence of ALC on TNF-alpha levels was detectable. These data suggest that the host's immune responses to M. tuberculosis infection can be selectively modulated by drugs acting on the neuroendocrine axis.

A 23-year-old woman presented with a hyperkertotic erythematous plaque on her left thigh. It had appeared 5 years previously, and its appearance and size had remained stable. She was in good health and had no other medical problems. There was no family history of dermatological disorders. On physical examination, a single plaque on the posterior region of the left thigh was seen. It was erythematous, slightly scaly and with islands of noninvolved skin within the affected area (Fig. 1). The lesion was accompanied by slight itching. Nails, hair, mucosa, palms and soles showed no changes. Laboratory investigations, including complete blood cell count and serum chemistry were normal. Serological testing for human immunodeficiency virus (HIV) was negative.

Pier Giuseppe Agostoni, Milano Marina Aiello, Parma Nicolino Ambrosino, Gussago Eleftherios Anevlavis, Nea Ionia Veena B. Antony, Indianapolis, Ind. Lorenzo Appendini, Veruno Hormoz Ashtyani, Hackensack, N.J. I. Azziz, Edmunds Philip Bardin, Clayton, Melbourne Harry Bassaris, Patra Eric Bateman, Groote Schuur, Cape Town Robert P. Baughman, Cincinnati, Ohio Egmont Baumgartner, Hall, Tirol F. Xaver Baur, Hamburg Robert Berent, Wels Sten Erik Bergstrom, Huddinge Andrea Bianco, Napoli Sebastiano Bianco, Milano Roland Bittner, Berlin Francesco Blasi, Milano Annette Boehler, Zurich Thomas Boehm, Zurich Josef R.M. Bolitschek, Linz T. Bombeli, Zurich Louis-Philippe Boulet, Sainte-Foy Henri Bounameaux, Geneve Demosthenes E. Bouros, Athens Homer A. Boushey, San Francisco, Calif. Lennart Braback, Sundsvall Thomas Brack, Zurich Aidan Bradford, Dublin Christian Brambilla, Grenoble Antonio Braschi, Pavia Otto M. Braun, Horn O. Brandli, Faltigberg Vita Brusasco, Genova Martin H. Brutsche, Basel Jean-Luc Burgaud, Sophia Antipolis Andrew Bush, London Cecilia Calabrese, Napoli Philippe Camus, Dijon Pier Aldo Canessa, Sarzana, La Spezia Laura Carrozzi, Pisa Antonio Castagnaro, Mantova Sergio Cavaliere, Brescia M. Cazzola, Napoli I. Cerveri, Pavia Pascal Chanez, Montpellier Neil S. Cherniack, Newark, N.J. Alfredo Chetta, Parma Gianfranco Chiari, Parma Luke Clancy, Dublin Enrico Clini, Gaiato dei Pavullo Henri Colt, La Jolla, Calif. J.H. Coote, Birmingham Giuseppe M. Corbo, Roma Antonio Corrado, Firenze Paolo Coruzzi, Parma U. Costabel, Essen J. Costello, London Nunzio Crimi, Catania Isidor Dab, Bruxelles Roberto Dal Negro, Bussolengo Filiberto Dalmasso, Torino Peter Dalquen, Basel Peter Davies, Liverpool Fernando De Benedetto, Chieti Francesco de Blasio, Arco Felice Marc Decramer, Leuven P.N. Richard Dekhuijzen, Nijmegen Jose Pablo Diaz Jimenez, Barcelona Robert Dinwiddie, London Peter Dorow, Berlin Keith Dorrington, Oxford Roberto Duranti, Firenze Michael Dusmet, London J. Eckmayr, Wels B. Emmerich, Munchen Armin Ernst, Boston, Mass. Santiago Ewig, Bonn H. Fabel, Hannover A. Fairfax, Stafford Franco Falcone, Bologna Rudolf Ferlinz, Bad Gastein Jean-William Fitting, Lausanne Pierre Fournel, St. Etienne Lutz Freitag, Hemer Dimitris Georgopoulos, Heraklion Vassilis Georgoulias, Heraklion Helen Giamarelou, Marousi, Athens Simon Godfrey, Jerusalem A. Greening, Edinburgh Paul Haber, Wien Dean Handley, Marlborough, Mass. Patricia L. Haslam, London W. Heindl, Wien Arthur Helbling, Bern Bill Hesselmar, West Perth Richard Hodder, Ottawa J.C. Hogg, Vancouver Rudolf Maria Huber, Munchen Gerard Huchon, Paris David W. Hudgel, Detroit, Mich. Stasia Jastrzembski, Newark, N.J. Amal Jubran, Maywood, Ill. Frank Kanniess, Grosshansdorf Jack Kastelik, Cottingham, East Yorkshire Philipp Kaufmann, Zurich Roland Keller, Aarau Frank Kelly, London Paul Kemp, Leeds Ok Hwa Kim, Kyonggi-do Carl M. Kirsch, San Jose, Calif. Nikolaus Konietzko, Essen D. Kohler, Schmallenberg-Grafschaft Richard Kraemer, Bern Claus Kroegel, Jena Friedrich Kummer, Wien Boris Lams, London Irene Lang, Wien Didier Lardinois, Zurich R. Lazor, Geneve Ph. Leuenberger, Lausanne Brian Lipworth, Dundee H. Lode, Berlin Stelios Loukides, Athens Maurizio Luisetti, Pavia Piero Maestrelli, Padova H. Magnussen, Grosshansdorf Katerina Malagari, Papagou, Athens Carlo Manca, Parma Milan Marel, Praha Charles-Hugo Marquette, Lille C. Marriott, London Praveen N. Mathur, Indianapolis, Ind. Heinrich Matthys, Freiburg/Br. Harald Mauch, Berlin Thomas Meisl, Wien Giovanni Migliori, Tradale M. Miniati, Pisa Anna Maria Moretti, Bari A.H. Morice, Cottingham Gianna Moscato, Pavia Michael Rolf Mueller, Wien

This report presents the results of a study designed to verify the influence of lens opacities on the visual field indices. Four age-matched groups of subjects were considered: healthy volunteers, glaucomatous patients without lens opacities, cataractous patients without glaucoma and glaucomatous patients with lens opacities. The quantification of lens opacities was performed with the Lens Opacity Meter 701 instrument. The visual field indices were obtained automatically from the G1 program of the Octopus system. The statistical analysis of the results (coefficient of correlation) has shown that only the visual field indices that correspond to uniform and diffuse loss of light sensitivity were influenced by the presence of cataract. On the contrary, the visual field indices that indicate local irregularities of the threshold were not significantly influenced by the presence of lens opacities.

The role of bacterial lipopolysaccharides (LPS) has been evaluated for their influence on the human T cell-mediated anti-Salmonella typhi activity. In nonendemic areas for salmonellosis this activity is exerted by CD4+ lymphocytes armed by IgA, whereas in endemic zones besides these cells also CD8+ lymphocytes armed by IgG display an elevated anti bacterial activity. These results suggest that, in endemic regions, continuous antigenic challenge and, in particular, that exerted by lipid A (the active moiety of LPS) may play a role in triggering this activity. In other series of experiments, pretreatment of endemic peripheral blood lymphocytes (PBL) with smooth and rough (Rb and Re) forms of Salmonella LPS leads to the inhibition of antibacterial activity. In this respect, Re-LPS, which contains lipid A covalently linked to the core-chetodeoxyoctonate, gives rise to the maximum of inhibition. Finally, fractionation of PBL by means of S. minnesota R345 (Rb) cytoadherence has led to the conclusion that anti bacterial activity is present in the Rb-unbound population, thus indicating that bacterial adherence to PBL is a distinct phenomenon from natural anti-S. typhi activity. The overall results suggest that lipid A is able to modulate the expression of antibacterial activity exerted by human peripheral blood T cells.