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Aortic root dilatation has been proposed as hypertension-mediated organ damage (HMOD). Nevertheless, the role of the aortic root dilatation as a possible additional HMOD is still unclear since studies conducted so far are quite heterogeneous regarding the type of population analyzed, the aortic tract considered, and the type of outcomes accounted for. The aim of the present study is to assess whether the presence of aortic dilatation is associated with strong cardiovascular (CV) events (MACE: heart failure, CV death, stroke, acute coronary syndrome, myocardial revascularization) in a population of patients affected by essential hypertension. Four hundred forty-five hypertensive patients from six Italian hospitals were recruited as part of ARGO-SIIA study1. For all centers, follow-up was obtained by re-contacting all patients by telephone and through the hospital's computer system. Aortic dilatation (AAD) was defined through absolute sex-specific thresholds as in previous studies (41 mm for males, 36 mm for females). Median follow-up was 60 months. AAD was found to be associated with the occurrence of MACE (HR = 4.07 [1.81-9.17], p < 0.001). This result was confirmed after correction for main demographic characteristics such as age, sex and BSA (HR = 2.91 [1.18-7.17], p = 0.020). At penalized Cox regression, age, left atrial dilatation, left ventricular hypertrophy and AAD were identified as best predictor of MACEs and AAD resulted a significant predictor of MACEs even after correction for these confounders (HR = 2.43 [1.02-5.78], p = 0.045). The presence of AAD was found to be associated with an increased risk of MACE independently of for major confounders, including established HMODs. AAD ascending aorta dilatation, LAe left atrial enlargement, LVH left ventricular hypertrophy, MACEs major adverse cardiovascular events, SIIA Società Italiana dell'Ipertensione Arteriosa (Italian Society for Arterial Hypertension)., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: To date, few cases of multiple sclerosis (MS) patients with concomitant Human Immunodeficiency Virus (HIV) infection have been described. However, none of the previously described cases has been treated with Natalizumab, probably due to the increasing risk of progressive multifocal leukoencephalopathy (PML)., Case: We report the case of a patient concomitantly diagnosed for HIV infection and MS treated with combined antiretroviral therapy (cART) and Natalizumab for 19 months, without clinical or radiological MS activity., Conclusions: Our case might suggest considering Natalizumab in patients with concomitant HIV infection, especially for those with significant disease activity requiring a high efficacy disease modifying treatment., (© 2023. Fondazione Società Italiana di Neurologia.)

Few data are available on the impact of COVID-19 vaccination on CD4 counts and HIV-RNA in persons living with HIV (PLWH). We present the data of 235 PLWH who were vaccinated with BNT162b2 in March 2021-February 2022 at the "Cotugno" hospital in Naples. PLWH treated at the "Cotugno" hospital, who were vaccinated at the hospital vaccination center, without prior COVID-19 and for whom immunological/virological data were available in the last 12 months and in the 6 months after vaccination were included. Antispike Ab were available for 187 and 64 PLWH after the second and third doses: PLWH with antispikes >33 binding antibodies units (BAU)/mL increased from 91% to 98%. Antinucleocapsid Ab performed in 147 and 56 patients identified 19 (13%) asymptomatic/paucisymptomatic COVID-19 infections after the second dose and an additional 15 (27%) after the third dose. Immunological/virological data were collected before vaccination (T0), after the second dose (T1), and after the third dose (T2). The absolute number of CD4 increased after the third dose (median 663, 657, and 707 at T0, T1, and T2; p  < 0.000 T0 vs. T2). The proportion of patients with HIV-RNA <50 copies/mL increases significantly after the second dose (73%; 85.7%; 87.7%; p  < 0.000 T0 vs. T2). The presence of COVID-19 asymptomatic/paucisymptomatic infections (demonstrated by the presence of antinucleocapsid Ab) significantly increases SARS-CoV-2 antispike Ab after second dose, but not after third dose. Asymptomatic/paucisymptomatic COVID-19 infections do not have influence on CD4 cell number and HIV-RNA level. Similarly, the presence of not-controlled HIV-RNA (HIV-RNA >50 copies/mL) does not influence antispike Ab response. According to our data, the response to SARS-CoV2 vaccination is effective in people living with HIV. Vaccination against COVID-19 appears to positively affect immunological and virological levels in people living with HIV.

Background: Adherence to Anti-Retroviral Therapy (ART) is crucial for People Living With HIV (PLWH). In Italy, ART is delivered by Hospital Pharmacies, on a renewable prescription from the hospital physician. The measurement of package-refill (the rate of ART packages actually collected out of those to be collected in order to comply with therapy) is an effective tool to evaluate the adherence.During COVID-19 outbreak, at "D. Cotugno" hospital in Naples, Italy, the ART delivery policies have been adapted, in order to reduce the number of patients' access. We analysed the impact of these changes on the pill-refill of ART in January-August 2020, compared with 2018-2019., Methods: "D. Cotugno" hospital is a mono-specialistic Infectious Diseases hospital, caring for about 2500 PLWH. Since February 2020, the hospital was almost entirely dedicated to COVID-19 patients. All out-patient activities were interrupted, except for those dedicated to HIV/AIDS patients.In this preliminary study we included all patients assigned to one of the three Medical Divisions dedicated to HIV, who were already under treatment since at least 2017. Rate of package-refill was obtained by the Hospital Pharmacy registry, demographic and clinical data were derived from clinical database.During COVID-19, many measures were adopted in order to increase safety of PLWH attending to hospital. Among these, medical prescription validity increased from 4 to 6 months, and number of packages to be collected increased from 2 to 4, adopting a multi-month dispensing strategy.Package-refill is adequate if at least 95% of ART have been actually collected; partial and inadequate if 75%-94% or less than 75% of ART, respectively, have been collected. Package-refill was measured during the first year of COVID-19 (March 2020 - February 2021), compared to the same period in the two years before., Results: A total of 594 PLWH were included. PLWH with optimal pill-refill significantly increased in 2020-21 compared to 2018-2020 (62% vs 55%, p 0.013)., Discussion: Due to COVID-19, we would have expected a reduction in ART deliveries. Surprisingly, the opposite occurred. The increase of pill-refill rates may be due to different reasons, but we hypothesized that the adaption of delivery policies, with a higher number of packages allowed to be collected, strongly contributed to this result. This study suggests that multi-month dispensing policies may contribute to the improvement of adherence among PLWH., Competing Interests: Conflict of interest disclosure All authors declare to have not conflicts of interest about the contents of the study.

Extracellular vesicles (EVs) are of great interest to study the cellular mechanisms of cancer development and to diagnose and monitor cancer progression. EVs are a highly heterogeneous population of cell derived particles, which include microvesicles (MVs) and exosomes (EXOs). EVs deliver intercellular messages transferring proteins, lipids, nucleic acids, and metabolites with implications for tumour progression, invasiveness, and metastasis. Epidermal Growth Factor Receptor (EGFR) is a major driver of cancer. Tumour cells with activated EGFR could produce EVs disseminating EGFR itself or its ligands. This review provides an overview of EVs (mainly EXOs and MVs) and their cargo, with a subsequent focus on their production and effects related to EGFR activation. In particular, in vitro studies performed in EGFR-dependent solid tumours and/or cell cultures will be explored, thus shedding light on the interplay between EGFR and EVs production in promoting cancer progression, metastases, and resistance to therapies. Finally, an overview of liquid biopsy approaches involving EGFR and EVs in the blood/plasma of EGFR-dependent tumour patients will also be discussed to evaluate their possible application as candidate biomarkers.

Background: HCV-related liver disease is an important cause of morbidity and mortality in patients with HIV infection. It is well known that the response rates to HCV therapy are similar between HCV-monoinfected patients and HIV-HV coinfected ones. The aim of this study was to evaluate the impact of HCV eradication on CD4 + T cell count in a population of HIV-HCV coinfected patients., Materials and Methods: We enrolled patients with HIV-HCV coinfection attending the Infectious Diseases Unit of the A.O.U. Federico II of Naples, from January 2016 to February 2019, treated with ART (AntiRetroviral Therapy) and DAAs (Direct Antiviral Agents). For each patient, we evaluated HIV and HCV viral load and CD4+ T cell count before starting therapy with DAAs, by SVR12 time and by SVR48 time. Fibrosis was evaluated by the mean of Fibroscan ® ., Results: Fifty-two patients were enrolled, 40 males. Fibrosis score was F0-F3 in 15 patients and cirrhosis in the remaining 11 (all in Child-Pugh class A). All had been receiving ART, and all were treated with DAAs. Only patient who had not achieved HIV viral suppression for non-compliance also experienced a relapse of HCV infection after the end of DAAs. In all patients, we observed that the CD4+ T cell count at baseline did not show significant variations compared to SVR12 and SVR48 time. We also assessed CD4 count in relation to HIV categories and stage of liver disease, see Table 1. Also, based on the assessments of the subclasses considered, there were no significant changes in the CD4 + T cell count., Conclusion: Our study shows that HCV viral eradication obtained with DAAs in patients with HIV-HCV coinfection is not associated with significant changes in the CD4 + T cell count, regardless of CDC category and stage of liver disease., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Pinchera et al.)

Background: The aim of the present study was to evaluate in HIV-infected patients treated with a direct-acting antiviral agent (DAA)-based regimen the variables associated with sustained virological response (SVR) and the trend in biochemical parameters and clinical events during and after DAA regimen., Methods: We performed a multicentre retrospective cohort study, enrolling all 243 HIV-HCV-coinfected adult patients treated with DAAs between January 2015 and December 2018 in one of the nine participating Infectious Disease Centers in southern Italy, eight in Campania and one in Apulia., Results: Of the 243 patients enrolled, 233 (95.9%) obtained an SVR at 12 weeks (SVR12). Of the 10 patients with non-SVR, 7 were tested for NS3, NS5A and NS5B resistance-associated substitutions (RASs) by sequencing analysis and 6 showed at least 1 major RAS in 1 HCV region (all in NS5A, 2 in NS5B and 1 in NS3). Comparing the 233 patients achieving SVR and the 10 non-achievers, no variable was independently associated with non-SVR. During and after DAA regimen, no modification in the biochemical parameters and clinical events was observed; however, the serum cholesterol and low-density lipoprotein (LDL) levels showed an increase (from 159 ±41.3 mg/dl at baseline to 174 ±44.5 mg/dl at week 12 after stopping treatment, P<0.001, and from 92 ±34.6 mg/dl to 109.4 ±73.7 mg/dl, P=0.002, respectively)., Conclusions: The treatment with DAAs led to a high SVR12 rate in HIV-HCV-coinfected subjects, irrespective of epidemiological, clinical or virological characteristics. However, the DAA regimen was associated with an increase in total- and LDL-cholesterol, to be taken into account in the management of HIV infection.

Study Hypothesis: Since the 1990s, Italian hospitals are required to comply with emergency disaster plans known as Emergency Plan for Massive Influx of Casualties. While various studies reveal that hospitals overall suffer from an insufficient preparedness level, the aim of this study was to better determine the preparedness level of Emergency Departments of Italian hospitals by assessing the knowledge-base of emergency physicians regarding basic disaster planning and procedures., Methods: A prospective observational study utilized a convenience sample of Italian Emergency Departments identified from the Italian Ministry of Health website. Anonymous telephone interviews were conducted of medical consultants in charge at the time in the respective Emergency Departments, and were structured in 3 parts: (1) general data and demographics, (2) the current disaster plan and (3) protocols and actions of the disaster plan., Results: Eighty-five Emergency Departments met inclusion criteria, and 69 (81 %) agreed to undergo the interview. Only 45 % of participants declared to know what an Emergency Plan for Massive Influx of Casualties is, 41 % believed to know who has the authority to activate the plan, 38 % knew who is in charge of intra-hospital operations. In Part 3 physicians revealed a worrisome inconsistency in critical content knowledge of their answers., Conclusions: Results demonstrate a poor knowledge-base of basic hospital disaster planning concepts by Italian Emergency Department physicians-on-duty. These findings should alert authorities to enhance staff disaster preparedness education, training and follow-up to ensure that these plans are known to all who have responsibility for disaster risk reduction and management capacity.

According to the World Health Organization, approximately 150 million people worldwide are chronic carriers of hepatitis C virus (HCV). HCV infection can evolve into cirrhosis of the liver and its complications, which are ultimately responsible for more than 350,000 deaths every year. Antiviral therapy, when successful, is able to decrease the rate of progression and increase survival. Two types of therapies are currently available, ie, interferon-based therapies and interferon-free ones. The latter have several advantages in terms of safety and tolerability, and could be used even in the most advanced stages of the disease. However, their use is restricted to some viral genotypes (genotype 2 and 3) and they are expensive. Several molecules are in an advanced phase of development. This review deals with the pharmacokinetics, pharmacodynamics, tolerability, and safety of asunaprevir, an inhibitor of HCV nonstructural 3 protease. Asunaprevir exerts optimal in vitro activity particularly against HCV genotypes 1 and 4, and its pharmacokinetic profile enables twice daily administration. The drawback of asunaprevir, and of all protease inhibitors, is its low barrier to resistance. Consequently, it is used in association with other drugs to prevent resistance. Specifically, when combined with daclatasvir, an NS5A inhibitor, asunaprevir results in a very high rate of viral eradication in both treatment-naïve and treatment-experienced patients, with a sustained virological response rate of 80%-90%. Tolerability is fair; in fact, asunaprevir is associated with a transient increase in aminotransferase levels, which is mild in most cases. In conclusion, asunaprevir is a good candidate component of interferon-free combinations and may revolutionize the treatment of chronic HCV infection in the near future.

In the early 1990s a reduction in the rate of sexually transmitted infections (STIs) occurred, although recent years have seen an increase. The aim of this study was to examine epidemiological and clinical features of syphilis cases in patients with HIV infection. We reviewed the charts of HIV-infected patients referring to our centre in the period 2002-2011. Fifty of the 402 consecutive HIV-positive patients (12.4%) received a diagnosis of syphilis. An increasing trend in the number of syphilis cases was observed within the period of the study. Most patients with syphilis (64%) presented a latent syphilis of unknown duration. About half of these received a concomitant diagnosis of HIV infection. Men who have sex with men (MSM) were the largest group. In the years 2002-2011, the incidence of syphilis in HIV-infected patients increased in our centre, notably among MSM. There is an urgent need for campaigns aiming to prevent STIs.

The treatment of HBV infection in patients with HIV co-infection presents several peculiar features: some drugs active against HBV are also active against HIV. This precludes their use in monotherapy in HIV-HBV co-infected patients due to the potential risk of selecting HIV-resistant strains. Telbivudine seemed to be a candidate for exclusive anti-HBV therapy because it exerts no significant in vitro activity against HIV. In this context, we describe the case of a HIV-HBV co-infected patient who presented indication for treatment only for HBV infection. After a short course of interferon treatment withdrawn due to adverse events, adefovir monotherapy was started. Since no significant viral drop was achieved during adefovir treatment, telbivudine was added. This treatment was associated with a complete virological response on HBV. It is noteworthy that after two months of this treatment even the HIV viral load presented a significant reduction. Our findings pose concerns of possible antiviral activity of telbivudine against HIV and therefore of selecting resistant mutations.

About 10% of the human immunodeficiency virus (HIV) patients show thrombocytopenia. We describe the case of an HIV/HCV-positive patient whose autoimmune thrombocytopenia resolved with the addition of raltegravir to previous highly active antiretroviral therapy (HAART). It is noteworthy that the effect on platelet count appeared to be independent of viral load suppression, which was achieved with previous antiretroviral regimens. In fact, it has been suggested that the positive effect exerted by raltegravir on autoimmune diseases is due to its inhibition on herpes viruses, and hence on activation of endogenous human retroviruses. This consideration, if confirmed, could open new avenues in the treatment of autoimmune thrombocytopenia in the HIV setting.

A 59-year-old woman was admitted to our hospital because of atypical chest pain. Stress ECG test was inconclusive. The patient underwent contrast-enhanced 16-slice computed tomography which demonstrated the absence of left main, and separate but adjacent ostia of the left anterior descending artery (LAD) and the left circumflex artery (CX) from the left coronary aortic sinus of Valsalva and severe narrowing of their proximal tracts. Conventional coronary angiography confirmed the diagnosis. Some time later, the patient underwent coronary artery bypass graft by left internal mammary artery graft to the LAD and Y-saphenous vein bypass to the obtuse marginal branch of CX. Multislice computed tomography (MSCT) scan, 1 year later, revealed the patency of grafts. MSCT, with the aid of postprocessing techniques, is an accurate and precise, noninvasive tool for the visualization of coronary artery anatomy, identification of coronary stenoses and evaluation of coronary artery bypass grafts.

We present a case of a 59-year-old man who was admitted to the hospital because of atypical chest pain and dyspnea. Conventional coronary angiography showed an anomalous origin of the right coronary artery from the pulmonary trunk. The patient underwent multislice computed tomography in order to clarify the origin and course of the anomalous vessel. The aim of this report is to emphasize the role of multislice computed tomography as an accurate noninvasive imaging tool in the evaluation of coronary artery anomalies.

Background: Chronic hepatitis C affects about 3% of the world's population. Pegylated interferon (IFN) alpha plus ribavirin is the gold standard treatment. Methylenetetrahydrofolate reductase(MTHFR) is a key enzyme in the metabolism of homocysteine. MTHFR gene polymorphisms and high levels of homocysteine are associated with a high degree of steatosis and fibrosis, conditions associated with a low sustained virological response (SVR) rate., Aims: To evaluate whether MTHFR polymorphisms and homocysteine levels are predictors of the outcome of treatment in 102 prospectively enrolled patients with chronic hepatitis C naive to treatment., Methods: Patients were treated with pegylated interferon alpha-2b plus ribavirin. All patients underwent blood tests, assessment of homocysteine, vitamin B(12), folate, hepatitis C virus (HCV)-RNA levels, screening for MTHFR gene polymorphisms and liver ultrasound examination., Results: Homocysteine levels were deranged (>16 micromol/L) in 10.5% of MTHFR wild-type patients vs 40.3% of non-wild-type patients (P=0.015). Homocysteine levels were 14.4 micromol/L in SVR patients and 15.5 micromol/L in non-SVR patients (P=0.049). The SVR rate was 40.0% in MTHFR wild-type patients, 52.0% in heterozygote mutants and 39.3% in homozygote mutants (P=0.467). At logistic regression analysis, genotypes 2 and 3 (odds ratio: 12.328, 95% confidence interval: 3.390-44.837, P=0.0001), homocysteine <16 micromol/L (odds ratio: 3.397, 95% confidence interval: 1.033-11.177, P=0.044) and aspartate aminotransferase (AST) levels <48 U/L (odds ratio: 3.262, 95% confidence interval: 1.125-9.458, P=0.029) were independent predictors of SVR., Conclusions: In patients with chronic hepatitis C, homocysteine levels are associated with the outcome of pegylated-IFNalpha plus ribavirin treatment, while polymorphisms of MTHFR are not.

It is not known whether iron depletion before pegylated IFN or combination treatment improves sustained virological response (SVR) rate in patients with chronic hepatitis C, despite its use in clinical practice in this setting. We aimed to investigate whether blood letting improves the efficacy (SVR) and tolerability of PEG-IFNalpha2b + Ribavirin in chronic hepatitis C patients. Patients with chronic hepatitis C and ferritin >100 ng/mL were randomized to: (1) repeated phlebotomies to obtain a ferritin level <50 ng/mL followed by pegylated-Interferon alpha2b + ribavirin (active arm); or (2) pegylated-Interferon alpha2b + ribavirin (control arm). Primary endpoint was SVR rate, secondary endpoint was frequency of clinical and laboratory grade 3-4 adverse events. Thirty-three patients were enrolled in the study (19 in active arm, 14 in control arm). The 19 patients in the active arm underwent a median of 5 phlebotomies (range: 1-9) to achieve the targeted ferritin (<50 ng/mL). Phlebotomies significantly reduced ferritin, iron, transferrin saturation, aspartate aminotransferase, alanine aminotransferase, and hemoglobin levels. Platelet count significantly increased, whereas HCV-RNA levels remained unchanged. After antiviral therapy overall SVR was 31.6% in active arm and 21.4% in control arm (P = 0.698). Considering only the 18 patients who were naive to antiviral therapy, SVR was 60% in active arm versus 25% in control arm (P = 0.188). Tolerability, drug dose reduction or withdrawal were similar in the two arms. In conclusion phlebotomies do not increase the overall efficacy of antiviral therapy. However, the strong trend to higher SVR in naive patients undergoing phlebotomies warrants further investigation.

Anomalous origin of the circumflex coronary artery from the right sinus of Valsalva is the most common coronary anomaly. This anomaly is thought to be of little clinical significance without the presence of severe narrowing of the vessel. A 43-year-old woman was referred to our institution for evaluation of atypical chest pain and equivocal results of the exercise stress test. We decided to perform multislice computed tomography coronary angiography before any other invasive studies. The scan was performed with a 16-row scanner (Aquilion 16 CFX, Toshiba Medical Systems, Tokyo, Japan) after intravenous administration of non-ionic contrast material. Scans revealed that the circumflex coronary artery originated from the right sinus of Valsalva; the initial course was retro-aortic until it reached its target in the atrioventricular groove; peripheral distribution of the circumflex coronary artery was then normal. The anomalous vessel presented a significant stenosis in its proximal tract. Coronary angiography confirmed that the origin of the circumflex coronary artery was from the right aortic sinus and the significant stenosis of the proximal portion of this vessel. This case confirms the full capability and accuracy of multislice computed tomography with the aid of post-processing techniques in the identification and evaluation of the ectopic origin of the left circumflex coronary artery from the right sinus of Valsalva, displaying accurately the origin, size, course, and relationship of the anomalous vessel with respect to surrounding structures.

Background: The aim of the present study was to assess the in-stent restenosis and occlusion of coronary artery stents by multislice computed tomography (MSCT) compared with conventional coronary angiography in patients with atypical chest pain and not practicable/non-conclusive stress test., Methods: Between December 2004 and March 2006, 81 patients were scheduled and of these 72 (65 men, mean age 61 years) with 90 stents underwent MSCT angiography using a 16-slice scanner, Toshiba Aquilion 16, 8-12 months after stent placement., Results: Of the 90 stents, 71 (79%) could be assessed and 19 (21%) were excluded because the image quality at the stent level was incompatible with diagnostic assessment. This results in sensitivity, specificity, and positive and negative predictive values for all assessable stents in the identification of occlusion and/or in-stent restenosis of 82, 96, 87, and 94%, respectively. When the 19 uninterpretable stents were included in the analysis, the diagnostic accuracy of MSCT in detecting in-stent restenosis and occlusion resulted in a sensitivity of 82%, specificity of 71%, positive predictive value of 40%, and negative predictive value of 94%., Conclusion: The results of the study suggest that MSCT angiography is a useful method for evaluating patency/occlusion of large (>or=3 mm) coronary stents in symptomatic patients with atypical chest pain and concomitant not practicable/non-conclusive exercise or stress imaging test.

We have studied 35 single nucleotide polymorphisms (SNPs) in the interferon (IFN) pathway to determine their contribution to multiple sclerosis (MS) and hepatitis C virus (HCV) infection. A total of 182 patients with MS, 103 patients with chronic hepatitis C, and 118 control subjects were enrolled in the study. Of the 35 SNPs studied, 3 were in IFN-alpha receptor (IFNAR-1), 10 in IFN-alpha/beta receptor (IFNAR-2), 9 in Stat1, 5 in Stat2, and 8 in IFN regulatory factor-1 (IRF-1). Compared to controls, Stat1 gene polymorphisms were significantly more frequent in MS patients (rs# 2066802 OR = 7.46, 95% CI = 2.22-25.10; rs# 1547550 OR = 1.69, 95% CI = 1.01-2.81) and in HCV patients (rs# 2066802 OR = 5.95, 95% CI = 1.55-22.81; rs# 1547550 OR = 2.30, 95% CI = 1.24-4.24). Also one IRF-1 gene SNP was associated with MS (rs# 2070721 OR = 2.05, 95% CI = 1.03-4.09), and four IRF-1 gene SNPs were associated with HCV infection (rs# 2070721 OR = 2.59, 95% CI = 1.23-5.43; rs# 2070723 OR = 4.8, 95% CI = 1.26-18.20; rs# 2070728 OR = 9.81, 95% CI = 1.21-79.4; rs# 2070729 OR = 3.6, 95% CI = 1.23-10.48; rs# 839 OR = 4.67, 95%CI = 1.29-16.87). Characteristic nucleotide combinations on single chromosomes (haplotype) generated block structures, including SNPs, that differed between patients and controls. Using a permutation test to detect differences in haplotype distribution between groups, the CCATTGA and the CCGAA haplotypes in the IRF-1 gene were more frequent in MS (p = 0.03) and in HCV patients (p = 0.001) than in controls. In conclusion, our data show that genetic variants in the IRF-1 and Stat1 genes of the IFN pathway are associated with MS and HCV infection.

We describe a case of brainstem infection by Listeria monocytogenes with right oculomotor palsy and lip drop, facial hypoesthesia, left arm paresthesia, positive blood culture, and sterile liquor in a 63-year-old man. Magnetic resonance imaging revealed an isolated mesencephalic lesion. Localization of this kind accounted for 3% of 111 cases reviewed.

A 53-year-old woman admitted to our department for histologically proven chronic hepatitis C had previously been treated with pegylated interferon-alpha2b (PEG-IFN) plus ribavirin. Combination therapy had been withdrawn after 5 weeks because of severe anemia (hemoglobin 8.2 g/dl) despite a reduction in ribavirin dose. A second liver biopsy showed moderate chronic hepatitis with portoportal and portocentral bridges (Ishak score: grading 14/18, staging 4-5/6). Consequently, the patient was retreated with 1.5 microg/kg body weight weekly PEG-IFN and 1000 mg/day ribavirin. Ribavirin was withdrawn about 3 months later because of anemia. After 1 month of PEG-IFN alone, hemoglobin had decreased further to reach 7.9 g/dl; consequently IFN was stopped. An elevated reticulocyte count, indirect bilirubin concentration, and lactic dehydrogenase (LDH) concentration, and a positive direct Coombs test (IgG3, C3d also for panagglutinant irregular antibodies on eluate) led us to diagnose autoimmune hemolytic anemia (AHA). The patient received 1 mg/kg body weight/day prednisone, and all parameters normalized within 20 days. This is the first case of IFN-related AHA during PEG-IFN plus ribavirin therapy. Physicians should be aware that PEG-IFN can be the cause of AHA during a ribavirin-containing regimen for chronic hepatitis C.

The ARS Component B gene (EMBL ID: HSARS81S, AC: X99977) encodes a 9 kD non-glycosylated polypeptide (also known as SLURP-1, SwissProt/TrEMBL: P55000), a soluble member of the human Ly6/uPAR superfamily. ARS Component B gene mutations have been implicated in Mal de Meleda. In this study we show by immunohistochemistry that SLURP-1 (secreted Ly-6/uPAR related protein, the protein product of the ARS Component B gene) is localized to human skin, exocervix, gums, stomach and esophagus. In the epidermis, keratinocytes underlying the stratum corneum are highly positive for SLURP1 immunostaining and cultured keratinocytes secrete the expected 9 kD protein. Circulating SLURP1 is detected in human plasma and urine. In the mouse, expression is evident in skin, eye, whole lung, trachea, esophagus and stomach. Human ARS Component B mRNA expression is regulated by retinoic acid, epidermal growth factor and interferon-gamma. The tissue localization and the association with Mal de Meleda suggest that ARS Component B and its protein product SLURP1 are implicated in maintaining the physiological and structural integrity of the keratinocyte layers of the skin., (Copyright John Libbey Eurotext 2003)

We have discovered a new, potent, selective, and orally active oxytocin receptor antagonist, (2S,4Z)-N-[(2S)-2-hydroxy-2-phenylethyl]-4-(methoxyimino)-1-[(2'-methyl[1,1'-biphenyl]-4-yl)carbonyl]-2-pyrrolidinecarboxamide (compound 1). We report the biochemical, pharmacological, and pharmacokinetic characterization in vitro and in vivo of this compound. Compound 1 competitively inhibits binding of [3H]oxytocin and the peptide antagonist 125I-ornithine vasotocin analog to human and rat oxytocin receptor expressed in human embryonic kidney 293-EBNA or Chinese hamster ovary cells with nanomolar potency. Selectivity against vasopressin receptor subtypes is >6-fold for V1a and >350-fold for V2 and V1b. Compound 1 inhibits oxytocin-evoked intracellular Ca2+ mobilization (IC50 = 8 nM). Compound 1 has no intrinsic agonist activity at the oxytocin receptor. Oxytocininduced contraction of isolated rat uterine strips is blocked by compound 1 (pA2 = 7.82). In anesthetized nonpregnant rats, single administration of compound 1 by i.v. or oral routes causes dose-dependent inhibition of contractions elicited by repeated injections of oxytocin with ED50 = 3.5 mg/kg i.v. and 89 mg/kg p.o., respectively. Compound 1 significantly inhibits spontaneous uterine contractions in pregnant rats near term when administered intravenously or orally. We conclude that compound 1 is a potent, selective, and orally active nonpeptide oxytocin receptor antagonist, which is a suitable candidate for evaluation as a potential tocolytic agent for the management of preterm labor.

Some latent diseases, such as immune disorders, can appear during interferon-alpha (IFN-alpha) therapy. These disorders are difficult to predict because of their low prevalence in the general population. We describe a case of pernicious anemia (PA) in a patient affected by chronic hepatitis C and macrocytosis during IFN-alpha therapy. Hemoglobin (Hb) concentration reached 7.3 g/dl. Anti-intrinsic factor (IF) antibodies were present, but not antiparietal cell antibodies (APCA). Suspension of IFN-alpha and administration of vitamin B(12) resulted in normal Hb concentrations. This case is the first instance of early PA (at the second month of IFN therapy) in a patient affected by chronic hepatitis C. The only other case of PA in a patient affected by hepatitis C virus (HCV) infection occurred during the second year of maintenance IFN therapy. We recommend that particular attention be paid to such clinical and laboratory conditions as macrocytosis in administering IFN-alpha therapy for chronic hepatitis C.

A case of visceral Leishmaniasis in a renal transplant recipient is reported because of its peculiar clinical presentation: the presence of most clinical signs of the disease, such as high-grade fever, marked leucopenia, and splenomegaly, but persistent negativity of serology and of bone marrow smear. Forty days after the first bone marrow biopsy, the diagnosis was made possible by a second biopsy, and the treatment was started with antimonial compounds, which led to complete remission of symptoms. A relapse was observed 1 month after discontinuation of therapy, successfully treated with a new cycle of the same drug and allopurinol. The diagnosis of Leishmaniasis must always be considered in immunosuppressed transplant recipients with fever and leucopenia of unknown origin, even when serology and bone marrow smear are negative.