Interleukin-28B (IL-28B) single-nucleotide polymorphisms and interferon plus ribavirin treatment outcome in Italian chronically HCV-infected patients.

To determine the single or combined effect of both rs12979860 and rs8099917 SNPs on HCV treatment response, these variants were genotyped in samples from a cohort of 170 patients infected with different HCV genotypes (HCVGT). The favourable rs12979860 CC genotype was found only in patients with sustained or rapid virological responses (SVR/RVR) and at significantly high proportions in HCVGT1/4 SVR patients. A significant association was also found between the rs8099917 TT genotype and SVR in both HCVGT1/4 and HCVGT2/3 groups of patients. In contrast, we found that there was significantly more of the rs8099917 GG genotype in nonresponders (NR) than in SVR patients which suggests a good association of the minor homozygote GG with the lack of treatment response. The combination of rs12979860/rs8099917 CC/TT favourable genotypes was found only in SVR patients and matched the frequency observed for their rs12979860 CC genotypes alone. By contrast, the inverse unfavourable correlate rs12979860/rs8099917 TT/GG genotype was seen more in NR than in SVR patients as observed for the single GG genotype. This study confirms the impact of both rs12979860 and/or rs8099917 IL-28B SNPs on treatment-induced clearance of HCV-RNA and demonstrates that the rs12979860 CC genotype is stronger than rs8099917 TT genotype in predicting a positive treatment response in HCVGT1/4 patients. The unfavourable rs8099917 GG genotype seems to be more important in predicting the failure of treatment response independently from HCV genotype.

An Italian study on health-related quality of life and fatigue in patients with chronic fatigue syndrome and patients with chronic HCV virus infection: similarities and differences.

Severe fatigue and a significantly reduced health-related quality of life (HRQoL) have been described in patients with chronic fatigue syndrome (CFS) in comparison with patients affected by chronic hepatitis C (CHC) and other chronic medical conditions. We examined 39 CFS and 49 CHC patients to explore whether fatigue and a poor HRQoL represent a greater medical and social problem in CFS than in CHC. The severity of fatigue and the HRQoL were assessed using the Fatigue Impact Scale (FIS) and the Health Status Questionnaire Short Form-36 (SF-36), respectively. The statistical analysis showed both a higher score of fatigue and a lower HRQoL in CFS than in CHC patients. Furthermore, in CHC patients the FIS evaluation showed a significantly reduced score of the psychosocial domain in comparison with the other domains. Multivariate linear regression analysis revealed female gender as the most important positive variable in chronic hepatitis C patients for total score of FIS. In conclusion, CFS was associated with a severe and disabling fatigue and an impaired HRQOL. In particular, both fatigue and all aspects of HRQOL perceived by CFS patients were significantly impaired compared to CHC patients. Consequently, management of fatigue should be considered a priority in order to improve HRQOL in CFS patients. In CHC patients the impact of fatigue on HRQoL was less significant than in CFS patients, even though the FIS evaluation showed a significant impairment of the psychosocial domain.

Proteinuria in an African HIV-infected patient: effects of telmisartan.

Kidney disease remains a major comorbidity of HIV infection especially in subjects of African ethnicity. HIV-associated renal disease with overt proteinuria has been associated with poorer outcomes and increased mortality. Telmisartan, an angiotensin II receptor blocker partial agonist of the PPAR-? approved for the treatment of hypertension, seems to exert a nephro-protective effect independent of blood pressure reduction in the general population. But data are lacking in HIV-positive patients with proteinuria. A case is described of an HIV-positive African patient with severe proteinuria treated with telmisartan. This therapy allowed proteinuria to be improved. This case shows for the first time that therapy with telmisartan has renoprotective effects also in an African HIV-infected patient.

Psychophysical distress and alexithymic traits in chronic fatigue syndrome with and without comorbid depression.

Patients with chronic fatigue syndrome (CFS) often report a comorbid depressive disorder. Comorbid depression may negatively influence the long-term outcome of CFS therefore it must be correctly diagnosed and treated. The aim of the present study is to provide a clinical and psychometric assessment of CFS patients with and without depressive features. A comparative analysis between 57 CFS subjects (CDC, 1994), 17 of whom with a comorbid depression, and 55 matched healthy volunteers was assessed to evaluate the presence of any psychophysical distress and alexithymic traits, by means of Symptom Checklist-90-R (SCL-90R) and Toronto Alexithymia Scale (TAS-20). The severity of fatigue was also assessed in all CFS patients using the Fatigue Impact Scale (FIS). With regard to psychiatric comorbidity, the SCL-90R scores showed higher levels of somatic complaints in CFS patients than in healthy subjects, whereas augmented depressive and obsessive-compulsive symptoms were observed only in the depressed CFS subgroup. When comparing the TAS-20 scores, we observed a selective impairment in the capacity to identify feelings and emotions, as measured by the Difficulty in Identifying Feelings subscale (DIF), non-depressed CFS patients showing an intermediate score between depressed CFS and healthy controls. Finally, in terms of FIS scores, a statistical trend versus a higher fatigue severity in depressed CFS patients, with respect to non-depressed ones, was observed. In conclusion, comorbid depression in CFS significantly increased the level of psychophysical distress and the severity of alexithymic traits. These findings suggest an urgent need to address and treat depressive disorders in the clinical care of CFS cases, to improve social functioning and quality of life in such patients.

Severe HIV-associated hypertriglyceridaemia treated with rosuvastatin plus omega-3 fatty acids.

Compared with healthy controls, HIV patients already have abnormal lipoprotein concentrations before the initiation of highly active antiretroviral therapy (HAART), which worsen with the therapy. HAART-associated dyslipidaemia features fundamental proatherogenic changes such as increased plasma triglycerides (TGs), increased total cholesterol and low-density lipoprotein cholesterol as well as decreased high-density lipoprotein cholesterol (HDL-C). The current guidelines for managing HIV-associated dyslipidaemia recommend diet and exercise counselling, alteration of HAART regimen or addition of lipid-lowering medications such as statins, fibrates and omega-3 (OM-3) fatty acids. Given that cardiovascular risk significantly increases with elevated lipid levels, selecting a drug to manage dyslipidaemia is particularly important. A case is described of an HIV patient who had severe hypertriglyceridaemia and bad metabolic parameters treated with rosuvastatin and OM-3 fatty acids. So we obtained a more marked reduction of TG levels than has never been described before in the literature, associated with a significant increase in HDL-C levels.

Acute urinary retention due to HSV-1: a case report.

Complications in urinary tract nervous routes due to herpes viruses as VZV and HSV-2 are well known. Acute urinary retention and chronic neuropathic pain are not rare when sacral dermatomes are involved by these viruses. However, an analogous condition has not yet been clearly ascribed to HSV-1 infection. We present a 32-year-old immunocompetent patient with fever, lumbar pain and acute urinary retention who had never had herpetic clinical manifestations. Urodynamic studies diagnosed a neurologic bladder with an absent filling sensation. Cystoscopic assessment revealed the presence of reddened and isolated small mucosal areas in the bladder walls. The search for herpes viruses in plasma and CSF by PCR assay were positive for HSV-1. After treatment with antiviral therapy the disease resolved. Intermittent catheterization was necessary and voiding dysfunction resolved after three weeks by its appearance. Neurological damage to the central nervous system (CNS) and/or PNS due to HSV-1 seems to be the most likely reason. The course of disease was benign and self-remitting.

Metabolic syndrome and cardiovascular risk in HIV-infected patients with lipodystrophy.

In this cross-sectional study, we evaluate potential predictors of Metabolic Syndrome (MS) in a group of 54 Caucasian chronically HIV-infected patients with lipodystrophy. According to ATP-III criteria, 22 patients were affected by MS and 32 were not. The mean age of the sample was 41.2+/-8.6 years, and most patients were males (74.1%); the two groups were homogeneous for gender, age, viro-immunologic status and the duration of antiviral therapy. The independent association between MS and several factors including demographic characteristics, type of highly-active antiviral therapy (HAART), viro-immunologic response, common cardiovascular risk factors (including Framingham scores), and selected cytokines (IFN-gamma, TNF-alpha, IL-2, IL-4, IL-6, IL-10 and IL-18), was investigated using stepwise forward logistic regression. At multivariate analysis, the only independent predictors of the metabolic syndrome were triglycerides and IL-18. A 10 mg/dL increase in triglycerides corresponds to an adjusted risk ratio for MS of 1.11 (95 percent IC: 1.04-1.19); and patients in the top tertile of IL-18 (those with IL-18 >/= 530 pg/L) had more than three times the likelihood of MS, as compared to the bottom and medium tertiles of IL-18 (patients with IL-18< 530 pg/L). This relationship was not attenuated by the inclusion of any other variable in the multivariate model. However, the association between metabolic syndrome and IL-18 is no longer significant when IL-18 is treated as a continuous variable (trend p = 0.087). Our results on HIV patients with lipodystrophy confirm previous findings on a strong independent association between IL-18 and MS in the general population. Further research is needed to clarify the mechanism of this association and its role in the development of cardiovascular disease in HIV patients.

The association of chronic hepatitis B and myopathy.

In two patients with chronic hepatitis B and myopathy, muscle biopsy showed necrosis and scarce inflammatory infiltrates. CD8+ cells surrounded some non-necrotic fibers. Hepatitis B virus (HBV) DNA and antigens were found inside intact muscle fibers. Major histocompatibility complex class I antigens were coexpressed with viral antigens. In one patient, symptoms improved during antiviral therapy. HBV can infect muscle fibers and an immune-mediated response to viral antigens may cause muscle injury.

Submaximal aerobic exercise with mechanical vibrations improves the functional status of patients with chronic fatigue syndrome.

AIM: Chronic fatigue syndrome (CFS) is an illness characterised by disabling fatigue of uncertain aetiology and other nonspecific symptoms. Typically CFS patients complain of a severe fatigue made worse by exercise, with a consistent reduction of working activity. A physical deconditioning could explain CFS features as well as a neuromuscular dysfunction, of central or peripheric origin. METHODS: Ten CFS patients were enrolled in a protocol of a rehabilitative treatment over a six-month period: they underwent a submaximal and predominantly aerobic exercise with a reduced O2 consumption using a Galileo 2000 system that provides mechanical vibrations characterised by sinusoid vertical sollecitations. Before and after such treatment, all patients underwent a pressure pain thresholds profile, an evaluation of physical and psychosocial parameters using the visual analogue scale (VAS) of Scott-Huskisson, and a muscle performance analysis by the CIBEX 6000 dynamometer. RESULTS: After the six-month period of study there was an overall improvement of the above described parameters as compared to the basal determinations. CONCLUSION: We conclude that the rehabilitative exertion provides an useful treatment for CFS patients particularly to realize an effective training of the explosive strength.

Correlation between animal and human brucellosis in Italy during the period 1997-2002.

The aim of this study was to test the hypothesis that brucellosis in Italy is a food-borne, rather than an occupational disease. This hypothesis was tested using data for both human and animal populations from the period 1997-2002. The correlation between the distribution of the disease in the human, sheep and goat populations was analysed, as were the risk factors for the disease, with respect to gender, age, occupation and residence of the individuals involved. Notifications of human brucellosis, which are mandatory in Italy, reach a peak between April and June. However, considering the standard incubation period of 2-4 weeks, and the fact that lamb slaughter is traditionally at a peak during the Easter period, it might be expected that occupational exposure would result in a peak of human cases between March and May. The observed peak between April and June could be related to the production and consumption of fresh cheese, starting just after lamb slaughter. The age of patients showed a fairly uniform distribution, and analysis of incidence rates of human brucellosis between 1997 and 2002 showed that the incidence rates were consistent with an occupational exposure risk of about 25%.

Study of immune alterations in patients with chronic fatigue syndrome with different etiologies.

The Chronic Fatigue Syndrome (CFS) is characterized by symptoms lasting for at least six months and accompanied by disabling fatigue. The etiology of CFS is still unclear. At the National Center for Study of the Infectious Diseases Department of the Chieti University some immune investigations were performed with the purpose of detecting markers of the disease. CD4+, CD8+, NK CD56+ and B CD19+ lymphocytes were studied in 92 male and 47 female patients and in 36 control subjects. CFS patients were divided in three groups with a post-infectious onset (PI-CFS), an non post-infectious onset (NPI-CFS) and a non post-infectious onset with associated infections (NPI-CFS + AI). Both CD4+ and CD8+ lymphocytes were reduced in the CFS patients. However, the CD4+/CD8+ ratio was increased in the CFS patients without difference between males and females. CD56+ cells of CFS patients were also reduced. In particular, blood CD56+ cells counts were significantly higher in PI-CFS patients than in the NPI-CFS subjects. These data confirm our preliminary results suggesting a key-role of a dysfunction of the immune system as a precipitating and-or perpetuating factor of the syndrome.

Interleukin-4 and interferon-gamma production during HIV-1 infection and changes induced by antiretroviral therapy.

Several lines of evidence indicate that a switch of the cytokine pattern from a predominant type 1 (antiviral and cell mediated response) to type 2 (polyclonal humoral immune response) occurs during the course of Human Immunodeficiency Virus-1 (HIV-1) infection, and represents a key event in the progression of immunodeficiency and dysregulated immune activation. We proposed to further investigate this immunological aspect of HIV-1 disease, in naive and in patients treated with Highly Active Antiretroviral Therapy (HAART). The prototypic cytokines chosen were Interleukin (IL)-4 and Interferon-gamma (IFN-gamma), whose in vitro production was determined in mononuclear cell cultures stimulated with different T lymphocyte mitogenic agents (anti-CD3, Phytohaemoagglutin-P -PHA-, E. coli B04/035 Lipopolysaccharide -LPS-). We classified all the patients on the basis of the number of CD4+ lymphocytes and we found a progressive, even if not significant decrease in the baseline production of IFN-gamma with the progression of the immunodeficiency. The mean value of baseline IFN-gamma in the group of patients with CD4+>500 cells/microL was 7.79 +/- 3.1 pg/mL while in the group with CD4+<200 cells/microL it was 4.66 +/- 2.22. We didn't find significant differences in the baseline production of IL-4 in these groups and in IFN-gamma and IL-4 production in LPS-stimulated cultures. We also re-assessed 12 patients after one year's follow-up. They presented a significant increase in IFN-gamma production compared to the first assessment in the LPS-stimulated cultures (baseline IFN-gamma 2.87 +/- 1.17 pg/mL, after 12 months 19.15 +/- 5.19 pg/mL; p= 0.03). In the 12 patients in follow-up IL-4 production showed a decreased in PHA-stimulated cultures with mean values of 16.65 +/- 14.32 pg/mL at baseline and 6.54 +/- 6.54 pg/mL after follow-up. These results highlight the immunorestoring effects of HAART. IL-4 production was lower in the treated subjects compared to the naive ones in PHA-stimulated cultures (mean values: IL-4=13.42 +/- 11.08 pg/mL in the naive patients and 9.75 +/- 65 pg/mL in the treated patients). The IFN-gamma values in anti-CD3 stimulated cultures were also higher in the treated patients, but this increase was not significant.

Hepatitis C virus infection and myositis: a virus localization study.

We report a case of myositis associated with chronic hepatitis C virus infection. Muscle biopsy and immunohistochemistry showed perifascicular atrophy, few necrotic and regenerating fibres, scarce perivascular infiltrates, deposits of immunoglobulin G, C3, fibrinogen and MAC in muscle vessel walls, and non-uniform expression of major histocompatibility complex-I antigens among muscle fibres. Hepatitis C virus NS3 antigen and hepatitis C virus RNA were detected in infiltrating cells but not within muscle fibres or endothelial cells. Our findings suggest that humoral-mediated immune mechanisms, not directly related to hepatitis C virus infection of muscle structures, may sustain the local inflammatory reaction in this patient.

Low frequency of severe hepatotoxicity and association with HCV coinfection in HIV-positive patients treated with HAART.

BACKGROUND: Highly active antiretroviral therapy (HAART) is strongly effective in reducing morbidity and mortality in HIV-1-positive individuals. Its main drawback is the potential toxicity. Data on the frequency and determinants of severe hepatotoxicity in a clinical setting are still sparse. METHODS: This is a prospective study of HIV-1-positive individuals with known HBsAg and HCV-Ab serology. The study end point was progression to alanine aminotransferase (ALT) levels > or =200 IU/L after HAART initiation. Cumulative probability of progression to this end point was estimated by the Kaplan-Meier method. Crude and adjusted hazard ratios (HR) were estimated by proportional hazards regression model. RESULTS: One thousand two hundred fifty-five patients were included. HBsAg was found in 91 (7.2%), HCV-Ab in 578 (46.5%) patients; almost all injection drug users (451 of 482; 93.6%) were HCV-Ab positive. Sixty-one individuals progressed to the end point with a probability of 7.9% (95% confidence interval [CI], 5.6-10.0) of progression at 24 months from starting. Independent factors predicting progression to the end point were baseline ALT levels (HR, 5.29; 95% CI, 3.24-8.65; every 10 IU/L higher), HCV-Ab positivity (HR, 4.01; 95% CI, 1.48-10.85) or both HBsAg and HCV Ab positivity (HR, 3.85, 95% CI, 1.01-14.61), and previous non-HAART therapy (HR, 1.84, 95% CI, 1.04-3.42). Patients receiving stavudine-containing regimens had a lower risk than those receiving zidovudine-containing regimens (HR, 0.30, 95% CI, 0.12-0.71). CONCLUSIONS: There was a low risk of ALT > or =200 IU/L in our cohort. Hepatitis C coinfection and elevated ALT levels at HAART initiation are important predictors of progression to ALT > or =200 IU/L; stavudine-containing regimens were associated with a lower risk compared with zidovudine-containing regimens.

Chronic fatigue syndrome following a toxic exposure.

Chronic fatigue syndrome (CFS) is a clinical entity characterized by severe fatigue lasting more than 6 months and other well-defined symptoms. Even though in most CFS cases the etiology is still unknown, sometimes the mode of presentation of the illness implicates the exposure to chemical and/or food toxins as precipitating factors: ciguatera poisoning, sick building syndrome, Gulf War syndrome, exposure to organochlorine pesticides, etc. In the National Reference Center for CFS Study at the Department of Infectious Diseases of 'G. D'Annunzio' University (Chieti) we examined five patients (three females and two males, mean age: 37.5 years) who developed the clinical features of CFS several months after the exposure to environmental toxic factors: ciguatera poisoning in two cases, and exposure to solvents in the other three cases. These patients were compared and contrasted with two sex- and age-matched subgroups of CFS patients without any history of exposure to toxins: the first subgroup consisted of patients with CFS onset following an EBV infection (post-infectious CFS), and the second of patients with a concurrent diagnosis of major depression. All subjects were investigated by clinical examination, neurophysiological and immunologic studies, and neuroendocrine tests. Patients exposed to toxic factors had disturbances of hypothalamic function similar to those in controls and, above all, showed more severe dysfunction of the immune system with an abnormal CD4/CD8 ratio, and in three of such cases with decreased levels of NK cells (CD56+). These findings may help in understanding the pathogenetic mechanisms involved in CFS.

Chronic fatigue syndrome: circadian rhythm and hypothalamic-pituitary-adrenal (HPA) axis impairment.

Chronic Fatigue Syndrome (CFS) is a clinical condition characterized by a persistent or relapsing debilitating fatigue at rest, lasting more than 6 months, and made worse by exercise. At the present moment, there are three potential etiopathogenic factors: immunologic, viral and neuroendocrine. The purpose of our study was to evaluate possible alterations of the hypothalamic-pituitary-adrenal (HPA) axis in our CFS patients by studying the circadian rhythms of prolactin (PRL), thyrotropic hormone (TSH), adrenocorticotropic hormone (ACTH), and cortisol (CS). A total of 36 patients were enrolled according to the Centers for Disease Control and Prevention case-definition criteria. Twenty healthy subjects were included as controls. Blood samples were taken every 4 hours during a single 24-hour period. We performed a fluorometric enzyme immunoassay with serum PRL, cortisol and TSH, and an immunoradiometric assay with plasma ACTH. The circadian rhythms of PRL, TSH, ACTH and CS were statistically significant in both CFS and control groups. At 24:00 and 04:00 hrs the CFS patients showed lower ACTH levels than healthy subjects (p < 0.001); the PRL levels were higher at 04.00 h in CFS patients than in healthy subjects.

Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is a poorly understood disease characterized by mental and physical fatigue, most often observed in young white females. Muscle pain at rest, exacerbated by exercise, is a common symptom. Although a specific defect in muscle metabolism has not been clearly defined, yet several studies report altered oxidative metabolism. In this study, we detected oxidative damage to DNA and lipids in muscle specimens of CFS patients as compared to age-matched controls, as well as increased activity of the antioxidant enzymes catalase, glutathione peroxidase, and transferase, and increases in total glutathione plasma levels. From these results we hypothesize that in CFS there is oxidative stress in muscle, which results in an increase in antioxidant defenses. Furthermore, in muscle membranes, fluidity and fatty acid composition are significantly different in specimens from CFS patients as compared to controls and to patients suffering from fibromyalgia. These data support an organic origin of CFS, in which muscle suffers oxidative damage.

Usefulness of Leifson staining method in diagnosis of Helicobacter pylori infection.

The Leifson staining method was used to diagnose Helicobacter pylori infection and was compared to histology, culture, and the rapid urease test (RUT). Histology gave the best sensitivity (98%), compared to Leifson staining (97%), culture (92%), and RUT (85%) (P < 0.005). Leifson staining is a sensitive, rapid, economical method for diagnosis of H. pylori infection in dyspeptic patients.

Idiopathic chronic fatigue and chronic fatigue syndrome: a comparison of two case-definitions.

The aim of the study was to compare the signs and symptoms of individuals meeting two different definitions of chronic fatigue syndrome (CFS). Ninety-four patients fitting the eligibility criteria for idiopathic fatigue were enrolled into the study. Of the 94 patients, 48 met the 1988 definition of CFS, 20 the 1994 (but not the 1988) definition of CFS, and 26 met neither definition. The 1994 defined cases were more likely than 1988 defined cases, and non-syndromal individuals to be male, married, and high school educated. The 1994 cases were less likely than 1988 cases to present acute onset, self reported sore throat, mild fever lymphadenopathy, pharyngitis. In conclusion, the 1994 criteria increased the number of patients classified as CFS; however, those who fit only the 1994 criteria were less likely to have an acute symptomatic onset and signs and symptoms suggestive of an infectious process.