Evolution of the prevalence of hepatitis C virus infection and hepatitis C virus genotype distribution in human immunodeficiency virus-infected patients in Italy between 1997 and 2015.

OBJECTIVES: To analyse the variation of hepatitis C virus (HCV) prevalence and genotype distribution and their determinants in people living with human immunodeficiency virus (HIV) who entered care between 1997 and 2015. METHODS: HIV-infected patients enrolled in ICONA who were tested for HCV antibodies (HCV-Ab) were included. RESULTS: Overall 3407 of 12 135 (28.1%) were HCV-Ab+; and 735 of 12 135 (6.1%) were HBsAg+. Among patients whose HCV genotype was known, the most represented were genotypes 1 and 3. The prevalence of HCV infection decreased from 49.2% (2565/5217) during 1997-2002 to 10.2% (556/5466) during 2009-2015. The frequency of genotype 1a increased from 29.0% (264/911) to 43.0% (129/300), whereas genotype 3 decreased from 38.5% (351/911) to 27.0% (81/300). Independent predictors of HCV-Ab+ status were being female (adjusted OR (AOR) 1.23, 95% CI 1.04-1.50, p = 0.01), risk category (versus injecting drug users: men who have sex with men AOR 0.01, 95% CI 0.01-0.01, p <0.001; heterosexuals AOR 0.01, 95% CI 0.01-0.01, p <0.001; other/unknown AOR 0.02, 95% CI 0.01-0.02, p <0.001), being cared for in Central Italy (versus being cared for in Northern Italy: AOR 0.85, 95% CI 0.73-0.98, p <0.001), being Italian-born (AOR 1.44, 95% CI 1.16-1.80, p = 0.001) and being enrolled in less recent calendar years (versus 1997-2002: 2009-2015 AOR 0.23, 95% CI 0.19-0.27, p <0.001; 2003-2008 AOR 0.49, 95% CI 0.41-0.61, p <0.001). CONCLUSIONS: The prevalence of HCV infection in HIV-infected patients entering into care in Italy significantly declined in more recent calendar years. After adjusting for risk factors and calendar years, HCV co-infection was more frequent in females and in those born in Italy.

Antimicrobial use and microbiological testing in district general hospital ICUs of the Veneto region of north-east Italy.

International - predominantly American - studies undertaken in the ICUs of teaching centres show that inadequate antibiotic therapy increases mortality and length of stay. We sought to ascertain whether this also pertains to smaller ICUs in the Veneto region of north-east Italy. To the best of our knowledge, this is the first such survey in the Veneto area or in Italy as a whole. A retrospective, observational study was performed across five general-hospital ICUs to examine appropriateness of microbiological sampling, empirical antibiotic adequacy, and outcomes. Among 911 patients (mean age, 65.8 years ± 16.2 SD; median ICU stay, 17.0 days [IQR, 8.0-29.0]), 757 (83.1 %) were given empirical antibiotics. Treatment adequacy could be fully assessed in only 212 patients (28.0 %), who received empirical treatment and who had a relevant clinical sample collected at the initiation of this antibiotic (T0). Many other patients only had delayed microbiological investigation of their infections between day 1 and day 10 of therapy. Mortality was significantly higher among the 34.9 % of patients receiving inadequate treatment (48.6 % vs 18.80 %; p < 0.001). Only 32.5 % of combination regimens comprised a broad-spectrum Gram-negative ß-lactam plus an anti-MRSA agent, and many combinations were irrational. Inadequate treatment was frequent and was strongly associated with mortality; moreover, there was delayed microbiological investigation of many infections, precluding appropriate treatment modification and de-escalation. Improvements in these aspects and in antibiotic stewardship are being sought.

Impulsivity modulates performance under response uncertainty in a reaching task.

We sought to explore the interaction of the impulsivity trait with response uncertainty. To this end, we used a reaching task (Pellizzer and Hedges in Exp Brain Res 150:276-289, 2003) where a motor response direction was cued at different levels of uncertainty (1 cue, i.e., no uncertainty, 2 cues or 3 cues). Data from 95 healthy adults (54 F, 41 M) were analysed. Impulsivity was measured using the Barratt Impulsiveness Scale version 11 (BIS-11). Behavioral variables recorded were reaction time (RT), errors of commission (referred to as 'early errors') and errors of precision. Data analysis employed generalised linear mixed models and generalised additive mixed models. For the early errors, there was an interaction of impulsivity with uncertainty and gender, with increased errors for high impulsivity in the one-cue condition for women and the three-cue condition for men. There was no effect of impulsivity on precision errors or RT. However, the analysis of the effect of RT and impulsivity on precision errors showed a different pattern for high versus low impulsives in the high uncertainty (3 cue) condition. In addition, there was a significant early error speed-accuracy trade-off for women, primarily in low uncertainty and a 'reverse' speed-accuracy trade-off for men in high uncertainty. These results extend those of past studies of impulsivity which help define it as a behavioural trait that modulates speed versus accuracy response styles depending on environmental constraints and highlight once more the importance of gender in the interplay of personality and behaviour.

Human cases of West Nile Virus infection in north-eastern Italy, 15 June to 15 November 2010.

In 2010, for the third consecutive year, human cases of West Nile virus (WNV) infection, including three confirmed cases of neuroinvasive disease and three confirmed cases of West Nile fever, were identified in north-eastern Italy. While in 2008 and 2009 all human cases of WNV disease were recorded in the south of the Veneto region, cases of WNV disease in 2010 additionally occurred in two relatively small northern areas of Veneto, located outside those with WNV circulation in the previous years. WNV IgG antibody prevalence in blood donors resident in Veneto was estimated as ranging from 3.2 per 1,000 in areas not affected by cases of WNV disease to 33.3 per 1,000 in a highly affected area of the Rovigo province. No further autochthonous human cases of WNV disease were notified in Italy in 2010. The recurrence of human cases of WNV infection for the third consecutive year strongly suggests WNV has become endemic in north-eastern Italy.

Septic shock, pneumonia, and soft tissue infection due to Myroides odoratimimus: report of a case and review of Myroides infections.

The genus Myroides comprises aerobic, yellow-pigmented, non-motile, non-fermenting gram-negative rods formerly classified as Flavobacterium odoratum. Members of the genus are widely distributed in the environment, especially in water, and usually behave as low-grade opportunistic pathogens, having been found to cause urinary tract infection, endocarditis, ventriculitis, and cutaneous infections in severely immunocompromised patients. We report a case of soft tissue infection, septic shock, and pneumonia due to M. odoratimimus in an immunocompetent male. To our knowledge, this is the first description of life-threatening infection caused by this organism in an immunocompetent host. We have also reviewed the medical literature on the genus Myroides.

Favourable evolution of virological and immunological profiles in treated and untreated patients in Italy in the period 1998-2008.

BACKGROUND: This study provides an estimate of the proportion of HIV-positive patients in Italian clinics showing an 'adverse prognosis' (defined as a CD4 count ≤ 200 cells/µL or an HIV RNA >50 HIV-1 RNA copies/mL) over time, and investigates whether this proportion varied according to patients' characteristics. METHODS: We estimated the annual proportion of patients with a CD4 count ≤ 200 cells/µL or HIV RNA > 50 copies/mL out of the total number of patients in the Icona Foundation cohort seen in any given year, both overall and after stratifying by demographical and treatment status groups. Generalized estimating equation models for Poisson regression were applied. RESULTS: In 1998-2008, the prevalence of patients with a CD4 count ≤ 200 cells/µL decreased from 14 to 6% [adjusted relative risk (RR) 0.86/year; 95% confidence interval (CI) 0.84-0.88; P<0.0001]. The prevalence of HIV RNA > 50 copies/mL decreased from 66 to 40% (adjusted RR 0.95/year; 95% CI 0.95-0.96; P<0.0001) in all patients and from 38 to 12% in the subgroup of patients who had previously received antiretroviral therapy (ART) for ≥ 6 months (adjusted RR 0.89/year; 95% CI 0.88-0.90; P<0.0001). CONCLUSIONS: There was a substantial increase in the success rate of ART in Italy in 1998-2008, resulting in a lower percentage of patients with adverse prognosis in recent years. The use of ART seemed to be the most important determinant of viral load outcome, regardless of mode of transmission. Although injecting drug users showed a less marked improvement in CD4 cell count over time than other risk groups, they showed a similar improvement in detectable viral load.

Clustering and risk factors of methicillin-resistant Staphylococcus aureus carriage in two Italian long-term care facilities.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a well-recognized agent of health care-associated infections in long-term care facilities, but few data about the circulation of MRSA in this setting in Italy are available. The aim of the study is to determine the prevalence and risk factors for MRSA carriage in nursing home residents in Vicenza (northeastern Italy). PATIENTS AND METHODS: A point prevalence survey was conducted in two long-term care facilities (subdivided into 15 wards) from 12 June 2006 to 6 July 2006. Anterior nasal swabs were obtained from residents and laboratory screening for MRSA was performed; full antibiotic susceptibility was assessed in MRSA isolates. Macrorestriction analysis of chromosomal DNA was carried out by pulsed field gel electrophoresis (PFGE). For each subject, demographic data, length of stay, dependency, cognitive function, presence of medical devices, comorbidities, current and previous antibiotic treatment, previous hospital admission and presence of infection were assessed on the day of sample collection. Factors that were found to be significantly associated with MRSA carriage at univariate analysis were introduced into multilevel logistic regression models in order to estimate the odds ratios (OR) with 95% confidence intervals (CI) for the risk of MRSA colonization, taking into account the clustering of patients within wards. RESULTS: Nasal swabs were obtained in 551 subjects; overall 43 MRSA carriers were detected (7.8%; CI = 5.7-10.4%). The rate of nasal carriers was very similar in the two institutions, and varied from 0% (0/36) to 18% (7/39) between wards. Only two out of 15 wards were found to have no MRSA carriers; overall, three pairs of colonized roommates were detected. Upon multilevel logistic regression, the risk of MRSA carriage was increased in patients with cancer (OR = 6.4; CI = 2.5-16.4), in those that had undergone recent hospitalization (OR = 2.2; CI = 1.0-4.4), and it reached OR = 4.0 (CI = 1.7-9.9) in those with three or more antibiotic treatments in the previous year; about 10% of the variability in MRSA carriage could be attributed to differences between wards. Pulsed field gel electrophoresis analysis permitted the definition of six clusters; two of these comprised 78.6% of the studied isolates and were quite similar, with one being more strongly represented among subjects hospitalized in the previous 12 months. All of the MRSA strains were resistant to ciprofloxacine; nevertheless, the majority were susceptible to most other non-betalactam antibiotics. CONCLUSION: The study suggests that nursing homes are a significant reservoir for MRSA. Statistical and PFGE analyses indicate a scenario where MRSA seems to be endemic and individual risk factors, namely recent hospitalizations and repeated antibiotic treatments, play a major role in the selection of drug-resistant organisms. Infection control measures should be coordinated among different health care settings, and the appropriate use of antibiotics has emerged as an important issue for improving the quality of care.

Prevalence and risk factors for nosocomial infections in hospitals of the Veneto region, north-eastern Italy.

OBJECTIVE: The study aimed to assess prevalence and risk factors for nosocomial infection (NI) in 21 hospitals of the Veneto Region (Italy). METHODS: In May 2003, a one-week-period prevalence study of NI was carried out in 21 hospitals, representing 63% of all hospital beds for acute patients of the Veneto Region. Intensive care units represented 84% of all intensive care beds of the Region. Long term care, neonatal intensive care, burn, psychiatric and dermatology units were excluded. RESULTS: Overall, 6,352 patients were surveyed. The prevalence of NI was 7.6% (range 2.6%-17.7%), while 6.9% of patients (range 2.6%-15.5%) were affected by at least one NI. The prevalence of patients with NI in medical, surgical and intensive care areas was 6.6%, 5.0% and 25.8%, respectively. The sites most frequently affected were the following: urinary tract (28.4%), surgical site (20.3%), blood stream (19.3%), pulmonary and lower respiratory tract (17.6%). At multivariate analysis risk factors independently associated to NI were: Charlson index score >1, severity of underlying disease, exposure to antibiotics, surgical intervention, trauma at admission, presence of central venous catheter >24 h, urinary catheter, intubation, tracheostomy, and duration since admission >15 days. CONCLUSION: The study provided baseline data of NI in the Veneto Region hospitals. It showed that NI are frequent, and display a wide inter-hospital variability of rates. The highest prevalence has been reported in intensive care units. The unusual high frequency of blood stream infections and the relatively lower prevalence rate of surgical site infections highlighted the limits of prevalence studies.

[Off-label antibiotic use: malpractice or good clinical practice?]. / La prescrizione off-label di antibiotici: malpractice o buona pratica clinica?

In Italy, off-label drug use has been forbidden since 1998. However, Italian law allows off-label treatment for single cases only if treatment is considered irreplaceable, and completely under physician responsibility. To assess the consequences of such regulations for the infectious diseases specialist, we listed the indications of intravenous and oral antibiotics available in our hospital pharmacy service, and discussed them in a pool of nine infectious diseases specialists. Indications were compared with the recommended treatment of major bacterial syndromes as suggested by the major guidelines and textbooks. We found that standard treatment for several bacterial infections is off-label. The pool of specialists concluded that some off-label use of antibiotics is vital to daily practice in infectious diseases. Scientific societies should promote guidelines as the standard reference for good clinical practice, which should not be based only on the respect of drug labels.

Linkage of microbiology reports and hospital discharge diagnoses for surveillance of surgical site infections.

Surveillance of surgical site infections (SSIs) with feedback to surgical personnel is pivotal in decisions regarding infection control. Prospective surveillance is time and resource consuming, so we aimed to evaluate a method based on data collected routinely during care delivery. The study was carried out at three acute hospitals in North-eastern Italy, from 1 January 2001 to 31 December 2001. Hospital discharge diagnoses (selected codes from the International Classification of Diseases, 9th Revision--Clinical Modification) and electronic microbiology reports (positive cultures from surgical wounds and drainages) were linked to identify suspected SSIs. A random sample of tracked events was submitted to total chart review in order to confirm the presence of SSIs retrospectively according to Centers for Disease Control and Prevention definitions. Of 865 suspected SSIs, 64.5% were identified from the microbiological database, 27.1% from discharge codes, and 8.4% from both. Four hundred and three admissions were sampled for review; the overall positive predictive value was 72% (95%CI=69-76%). Since inpatient individual antibiotic exposure is not registered in Italy, the combined use of discharge codes and microbiology reports represents the most feasible automated method for surveillance of SSIs developing during hospital stay.

Deep tissue biopsy vs. superficial swab culture monitoring in the microbiological assessment of limb-threatening diabetic foot infection.

AIMS: The results of ulcer swabbing vs. deep tissue biopsy have been compared prospectively in 29 diabetic patients with limb-threatening foot infection, to investigate the effectiveness and reliability of each method, and to evaluate whether any of the two could be more suitable for the microbiological follow-up of severe lesions. METHODS: Microbiological samples were collected by using both methods at fixed intervals after therapy commencement (i.e. at day 0, 7, 14, and 30). Statistical comparison was performed between the results of each sampling procedure after the end of follow-up. RESULTS: At enrolment, the mean number of isolates per patient was 2.34 by swabbing and 2.07 by tissue biopsy sampling; the rate of isolation for anaerobes with the two methods was 35% and 25%, respectively; no statistical differences could be observed between the two procedures in terms of either species or frequency of isolation. Anaerobic species were never detected after the first 2 weeks of appropriate treatment, and those ulcers which were still active at day 30 yielded almost exclusively Gram-positive bacteria. At the end of follow-up, deep tissue cultures appeared to exhibit a higher diagnostic sensitivity with respect to swabs. CONCLUSIONS: Swabbing and deep tissue cultures appear to be equally reliable for the initial monitoring of antimicrobial treatment in severe diabetic foot infection. However, our experience seems to suggest that deep tissue might be more sensitive than swabbing for monitoring those isolates that have been selected for antibiotic resistance, i.e. those from ulcers that are still active after 30 days of treatment.

Postoperative infections following total knee replacement: an epidemiological study.

From January 1991 to June 1997 217 patients undergoing monolateral or bilateral total knee replacement (TKR) were consecutively enrolled in a prospective study on the incidence of postoperative infections and related risk factors. Regional antimicrobial prophylaxis (teicoplanin 400 mg) was used in 263 (95%) prostheses implanted; in the remaining 14 implants (5%) perioperative antibiotic prophylaxis (teicoplanin 800 mg) was administered as usual by systemic route. None of the patients experienced local or systemic adverse effects. Over the 2-year follow-up period, 8 (2.9%) primary site infectious complications were recorded, i.e. 4 superficial infections, which were cured without involvement of the prostheses, and 4 deep infections, which required prosthesis removal. Six infections occurred in patients who had undergone previous surgery of the same knee joint, and 2 in patients undergoing primary TKR (p= 0.0005); diabetic patients had infections (13%) more frequently than non-diabetic patients (1.9%, p=0.01). Staphylococci were the leading organisms isolated from infections; however 3 strains of Escherichia coli were isolated from patients who had undergone a previous prosthesis implantation at the same knee joint. Regional administration of teicoplanin appears to be a safe and valuable prophylactic technique; however, in patients at risk of infection a prophylactic regimen which is also active against gram-negative bacteria should probably be considered.

Randomized prospective controlled trial of recombinant granulocyte colony-stimulating factor as adjunctive therapy for limb-threatening diabetic foot infection.

Adult diabetic patients admitted to our Diabetes Center from September 1996 to January 1998 for severe, limb-threatening foot infection were consecutively enrolled in a prospective, randomized, controlled clinical study aimed at assessing the safety and efficacy of recombinant human granulocyte colony-stimulating factor (G-CSF) (lenograstim) as an adjunctive therapy for the standard treatment of diabetic foot infection. Forty patients, all of whom displayed evidence of osteomyelitis and long-standing ulcer infection, were randomized 1:1 to receive either conventional treatment (i.e., antimicrobial therapy plus local treatment) or conventional therapy plus 263 microg of G-CSF subcutaneously daily for 21 days. The empiric antibiotic treatment (a combination of ciprofloxacin plus clindamycin) was further adjusted, when necessary, according to the results of cultures and sensitivity testing. Microbiologic assessment of foot ulcers was performed by both deep-tissue biopsy and swab cultures, performed at enrollment and on days 7 and 21 thereafter. Patients were monitored for 6 months; the major endpoints (i.e., cure, improvement, failure, and amputation) were blindly assessed at weeks 3 and 9. At enrollment, both patient groups were comparable in terms of both demographic and clinical data. None of the G-CSF-treated patients experienced either local or systemic adverse effects. At the 3- and 9-week assessments, no significant differences between the two groups could be observed concerning the number of patients either cured or improved, the number of patients displaying therapeutic failure, or the species and number of microorganisms previously yielded from cultures at day 7 and day 21. Conversely, among this small series of patients the cumulative number of amputations observed after 9 weeks of treatment appeared to be lower in the G-CSF arm; in fact, only three patients (15%) in this group had required amputation, whereas nine patients (45%) in the other group had required amputation (P = 0.038). In conclusion, the administration of G-CSF for 3 weeks as an adjunctive therapy for limb-threatening diabetic foot infection was associated with a lower rate of amputation within 9 weeks after the commencement of standard treatment. Further clinical studies aimed at precisely defining the role of this approach to this serious complication of diabetes mellitus appear to be justified.

Role of antigenemia assay in the early diagnosis and treatment of CMV infection in renal transplant patients.

AIM: CMV antigenemia by direct pp65 antigen detection and quantification was monitored on a weekly basis during the first 3 months after kidney transplantation. SUBJECTS AND METHODS: Preemptive therapy with ganciclovir was started according to the following criteria: any positive antigemia in CMV-NEG subjects, a single determination > or = 30 cell or a two fold increase of positive cells in two consecutive specimens in CMV-POS and continued until pp65 was cleared. Overall, 109 patients were monitored. RESULTS: Among the 24 CMV-NEG patients, 13 (54%) developed a pp65 positive assay without symptoms and were treated. Ten patients remained CMV-infection free and one patient developed late onset (7 months) CMV disease (hepatitis). Among the 85 POS patients 15 (17%) developed a pp65 positive assay and were treated. Two of them developed CMV disease within 7 days of the onset of positive antigenemia and 13 were asymptomatic. The other 70 patients remained CMV-infection free. The interval between transplant and the onset of CMV infection was 39 +/- 13 days in the CMV-NEG group and 64 +/- 20 days in the CMV-POS group (p < 0.001). The peak antigenemia level was 193 +/- 175 cells in the CMV-NEG group and 55+/- 78 cells in the CMV-POS group (p < 0.001). The duration of treatment did not differ in the two groups (22 +/- 7days). A second course of therapy, due to a relapse of asymptomatic infection was performed in 11/13 (85%) treated CMV-NEG patients and in 2/15 (13%) treated CMV-POS patients. CONCLUSIONS: Among the total 28 treated patients, we observed only 6 episodes of mild creatinine increase and 9 episodes of mild neutropenia. In the overall population, we observed 8 systemic infections not related to CMV.

Regional prophylaxis with teicoplanin in monolateral or bilateral total knee replacement: an open study.

From January 1991 to June 1997, patients undergoing primary elective monolateral or bilateral total knee replacement (TKR) were consecutively enrolled in a prospective, open clinical study on the efficacy and safety of regional prophylaxis with teicoplanin (TEC). Those scheduled for monolateral TKR (115 patients) received 400 mg of TEC in 100 ml of saline as a 5-min infusion into a foot vein of the leg to be operated on immediately after the tourniquet was inflated to 400 mm Hg (ca. 50 kPa). For patients undergoing bilateral surgery (45 patients), regional administration of TEC was also repeated for the second knee operation. Follow-up ranged from a minimum of 2 years to 8 years. None of the patients experienced local or systemic adverse effects following regional administration of TEC. In the immediate postoperative and 2-year follow-up periods, only one superficial infection of the primary site attributable to intraoperative contamination (prophylaxis failure) out of the 205 prostheses implanted was observed. Deep infections involving the prosthesis did not occur. Infectious complications at distant sites were observed in nine cases (urinary tract infection due to Escherichia coli in eight cases, and Salmonella enteritidis gastroenteritis in one case) in the immediate postoperative period; they all were rapidly cured after antibiotic treatment. A delayed prosthetic infection, related to hematogenous spread of the etiological agent and therefore not considered a prophylactic failure, was observed in a patient who had undergone TKR 5 years before. Regional administration of TEC in monolateral and bilateral TKR appears to be a safe and valuable prophylactic technique.

Effect of ursodeoxycholic acid administration in patients with acute viral hepatitis: a pilot study.

BACKGROUND: Ursodeoxycholic acid (UDCA) is able to improve biochemical markers of cholestasis, with a parallel decrease in transaminases, in various cholestatic liver diseases. AIM: To evaluate the effects of UDCA administration on acute viral hepatitis-related cholestasis and the course of acute viral hepatitis. METHODS: Seventy-nine consecutive patients with acute viral hepatitis (HBV: 43, HCV: 11, HAV: 15, HEV: 3, Non A-E: 7) were randomized to receive either UDCA for 3 weeks or no treatment. Liver biochemistry and serum bile acid determinations were run at weekly intervals. RESULTS: No significant differences were observed in mean percentage decreases in transaminases between treated and untreated patients. By contrast, cholestatic indexes decreased significantly more quickly in patients treated with UDCA than in controls, and this effect was more evident in patients with increasing alanine transaminase levels at admission. After a peak at the end of the first week of therapy, serum levels of conjugated ursodeoxycholic acid (CUDCA) showed a gradual decrease. Conjugated cholic acid (CCA) and chenodeoxycholic acid (CCDCA) showed a progressive decrease with the resolution of viral hepatitis, but no influence of UDCA administration was observed. CONCLUSIONS: Our study demonstrates that UDCA significantly improves cholestatic indices in patients with acute viral hepatitis, but this effect does not seem to affect the course of the illness.

Fibrogenesis serum markers in patients with chronic hepatitis C treated with alpha-IFN.

The correlation between therapeutic response and liver fibrogenesis was studied in serum and liver specimens taken from 31 patients treated with alpha-interferon (IFN) (14 sustained responders and 17 non-responders) for chronic hepatitis C. Serum samples, collected before therapy, and at further 6-month intervals over 2 years, were tested for markers of liver neofibrogenesis. Serum N-terminal procollagen III peptide (PIIINP) displayed a significant and persistent decrease (P < 0.05) in sustained responders but not in non-responders; significantly lowered (P < 0.05) mean levels of C-terminal procollagen I peptide (PICP) were transiently observed in both patient groups, apparently as a result of IFN administration. Serum laminin (Lam) levels remained unchanged. One year after the cessation of treatment, liver biopsy re-testing showed an improvement in necro-inflammatory scores only in sustained responders, with the histological fibrosis scores remaining unaltered in both groups. IFN treatment seemed to exert an influence on serum levels of markers of hepatic connective tissue turnover even in patients that did not respond to therapy, while no effect was observed on preexistent liver fibrosis.

Neural coding of finger and wrist movements.

Previous work (Schieber and Hibbard, 1993) has shown that single motor cortical neurons do not discharge specifically for a particular flexion-extension finger movement but instead are active with movements of different fingers. In addition, neuronal populations active with movements of different fingers overlap extensively in their spatial locations in the motor cortex. These data suggested that control of any finger movement utilizes a distributed population of neurons. In this study we applied the neuronal population vector analysis (Georgopoulos et al., 1983) to these same data to determine (1) whether single cells are tuned in an abstract, three-dimensional (3D) instructed finger and wrist movement space with hand-like geometry and (2) whether the neuronal population encodes specific finger movements. We found that the activity of 132/176 (75%) motor cortical neurons related to finger movements was indeed tuned in this space. Moreover, the population vector computed in this space predicted well the instructed finger movement. Thus, although single neurons may be related to several disparate finger movements, and neurons related to different finger movements are intermingled throughout the hand area of the motor cortex, the neuronal population activity does specify particular finger movements.