The benefits of hepatitis C virus cure: Every rose has thorns.

To examine mid-term benefits on hepatic complications, extrahepatic clinical syndromes and quality of life associated with HCV cure; to review the few safety issues linked to oral direct-acting antivirals (DAAs); and to discuss the potential population benefits of reducing the burden of HCV infection. DAAs cure HCV infection in more than 95% of patients. The halting of liver inflammation and fibrosis progression translates into both hepatic and extrahepatic benefits and reduces the need for liver transplantation. A reduction in the frequency of extrahepatic manifestations such as mixed cryoglobulinaemia and vasculitis and improvements in quality of life and fatigue have also been described. A few safety issues linked to DAAs such as the potential recurrence of aggressive HCC, the flares of hepatitis B virus in patients with overt or occult HBV infection are been discussed. Curing HCV infection also has a high potential to reduce the burden of HCV infection at the population level. With widespread scaling up of HCV treatment, several modeling studies suggest that major reductions in HCV prevalence and incidence are possible, and that elimination of viral hepatitis is an achievable target by 2030.

Skewed B cells in chronic hepatitis C virus infection maintain their ability to respond to virus-induced activation.

Chronic hepatitis C virus (HCV) infection is characterized by persistent B-cell activation, with enhanced differentiation and reduced proliferative ability. To assess the possible role of HCV in altering B-cell subset distribution, we examined ex vivo frequencies and B-cell inhibitory receptor expression in 37 chronic HCV-infected patients and 25 healthy donors (HD). In addition, we determined whether short-term exposure to culture-derived HCV (HCVcc) resulted in B-cell subset skewing and/or activation. There was a statistically significant increase in the frequencies of immature transitional, activated memory and tissue-like memory (TLM) B cells in HCV-infected patients compared with HD. We also found that the frequency of memory B cells correlated with serum HCV RNA levels. The proportion of B cells expressing the marker of exhaustion Fc receptor-like 4 (FcRL4) was generally low even though significantly higher in the patients' memory B-cell compartment compared with HD, and a positive correlation was found between the frequencies of the patients' TLM FcRL4+ B cells and serum alanine aminotransferase and histological activity index at liver biopsy. Exposure to cell-free HCVcc in vitro did not result in B-cell skewing but induced significant activation of naïve, TLM and resting memory B cells in HCV-infected patients but not in HD, in whom cell-associated virus was an absolute requirement for activation of memory B cells. These findings provide corroborative evidence in favour of significant B-cell subset skewing in chronic HCV infection and in addition show that expression of exhaustion markers in selected B-cell subsets does not impair virus-induced B-cell activation.

HCV E1E2-MF59 vaccine in chronic hepatitis C patients treated with PEG-IFNα2a and Ribavirin: a randomized controlled trial.

Hepatitis C virus (HCV) vaccines may be able to increase viral clearance in combination with antiviral therapy. We analysed viral dynamics and HCV-specific immune response during retreatment for experienced patients in a phase Ib study with E1E2MF59 vaccine. Seventy-eight genotype 1a/1b patients [relapsers (30), partial responders (16) and nonresponders (32) to interferon-(IFN)/ribavirin-(RBV)] were randomly assigned to vaccine (V:23), Peg-IFNα2a-180-ug/qw and ribavirin 1000-1200-mg/qd for 48 weeks (P/R:25), or their combination (P/R + V:30). Vaccine (100 µg/0.5 mL) was administered intramuscularly at week 0-4-8-12-24-28-32-36. Neutralizing of binding (NOB) antibodies and lymphocyte proliferation assay (LPA) for E1E2-specific-CD4 + T cells were performed at week 0-12-16-48. Viral kinetics were analysed up to week 16. The vaccine was safe, and a sustained virological response (SVR) was achieved in 4 P/R + V and 2 P/R patients. Higher SVR rates were observed in prior relapsers (P/R + V = 27.3%; P/R = 12.5%). Higher NOB titres and LPA indexes were found at week 12 and 16 in P/R + V as compared to P/R patients (P = 0.023 and 0.025, P = 0.019 and <0.001, respectively). Among the 22 patients with the strongest direct antiviral effects of IFN (ε ≥ 0.800), those treated with P/R + V (10) reached lower HCV-RNA levels (P = 0.026) at week 16. HCV E1E2MF59 vaccine in combination with Peg-IFNα2a + RBV was safe and elicited E1E2 neutralizing antibodies and specific CD4 + T cell proliferation. Upon early response to IFN, vaccinations were associated with an enhanced second phase viral load decline. These results prompt phase II trials in combination with new antiviral therapies.

Who is more likely to respond to dual treatment with pegylated-interferon and ribavirin for chronic hepatitis C? A gender-oriented analysis.

We assessed, in real-life practice, viral, demographic, genetic and metabolic factors influencing the sustained virologic response (SVR), with a gender-oriented analysis, in patients with chronic hepatitis C virus (HCV) treated with pegylated interferon and ribavirin. Six hundred and seventy naïve patients were treated with dual therapy and evaluated by gender and HCV genotype. Associations between baseline variables and SVR were assessed by multivariate logistic regression analysis. Among 362 genotype 1 patients, SVR was achieved in 158 patients (44%), and SVR was independently associated with age less than 50 years (OR 2.12; 95% CI 1.09-4.30; P=0.039) and C/C genotype rs12979860 SNP (OR 2.83; 1.19-6.74; P=0.002) in 163 females, while absence of visceral obesity (OR 2.491; 1.131-5.487; P=0.023), HCV-RNA lower than 400,000 IU/mL (OR 2.66; 1.273-5.558; P=0.009) and C/C genotype rs12979860 SNP (OR 4.969; 2.401-10.283; P<0.001) were independently associated with SVR in 199 males. Combining favourable baseline variables, the probability of obtaining SVR ranged from 27.6% to 84.2% in females, and from 14.3% to 85.7% in males. The rate of SVR was 81.1% in 175 genotype 2 patients, and 69% in 100 genotype 3 patients. Rapid virologic response was the only valid predictor of SVR regardless of other features. In conclusions, in the setting of HCV genotype 1, chronic hepatitis, combining rapid virologic response and predictive factors, which are different for females and males, allows clinicians to single out a group of patients whose likelihood of SVR exceeds 80%. For these patients, triple therapy with first-generation protease inhibitors may be unwarranted.

Consistence and discrepancy of neuropathic pain screening tools DN4 and ID-Pain.

Pain is a subjective condition that cannot be objectively measured; for this reason, self patient-perspective is crucial. Recently, several screening tools to discriminate between nociceptive and neuropathic pain have been developed. We aimed at assessing the consistence and discrepancy of two widely used screening tools, The Douleur Neuropathique 4 (DN4) and the 6-item questionnaire (ID-Pain), by comparing their ability in discriminating neuropathic from nociceptive pain. DN4 and ID-Pain were administered to 392 Italian patients attending 16 outpatient services for peripheral nerve diseases. Based on medical history, clinical findings and diagnostic tools, patients were divided into two groups (neuropathic and nociceptive). Globally, ID-Pain identified neuropathic pain in 60 % of patients (38 % probable, 22 % likely). Interestingly also DN4 diagnosed neuropathic pain in 60 % of cases. A discrepancy was observed in 16 % of cases. DN4 and ID-Pain resulted to be highly interrelated in the identification of neuropathic pain. Sensitivity of DN4 was 82 % and specificity was 81 %, while ID-Pain (considering both probable and likely groups) showed sensitivity 78 % and specificity 74 %. Reliable screening tools for neuropathic pain are well related between them; hence, they are available for researchers and clinicians who may choose the most appropriate for their activity. Since the gold standard for the diagnosis and treatment of neuropathic pain cannot do without a neurological evaluation, perhaps DN4, that includes physician objective measures, may help reducing the percentage of dubious cases. Conversely, when needing a more agile tool (not needing a physician) ID-Pain may be adopted.

Ulnar neuropathy at the elbow: how frequent is the idiopathic form? An ultrasonographic study in a cohort of patients.

OBJECTIVE: Ulnar neuropathy at the elbow (UNE) is the second most frequent focal neuropathy of the arm. The aim of our study was to establish the frequency of anatomical changes of the cubital tunnel capable of causing UNE. METHODS: Ninety-one consecutive patients affected by UNE, as established by neurophysiological studies, were enrolled in the study. All patients underwent ultrasonographic examination of the elbow, paying particular attention to the cubital tunnel, which was studied with either static or dynamic scans. RESULT: Fifty-four of the 91 patients (59.3%) had at least one anatomical alteration of the cubital tunnel. The changes observed in our patients were: subluxation of the ulnar nerve (18.7%), luxation of the ulnar nerve (9.9%), presence of osteophytes (6.6%), presence of accessory muscle (8.8%), articular ganglion (1.1%), post-traumatic lesions (3.3%), presence of osseous fragment (1.1%). CONCLUSIONS: A possible cause of ulnar nerve entrapment at the elbow was found in more than half of the patients. Joint ultrasonography is indispensable for the identification of such alterations as it allows for both static and dynamic evaluation of the ulnar nerve.

Severe acute respiratory syndrome coronavirus 2 RNA contamination of inanimate surfaces and virus viability in a health care emergency unit.

OBJECTIVES: To detect possible severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA contamination of inanimate surfaces in areas at high risk of aerosol formation by patients with coronavirus disease 2019 (COVID-19). METHODS: Sampling was performed in the emergency unit and the sub-intensive care ward. SARS-CoV-2 RNA was extracted from swabbed surfaces and objects and subjected to real-time RT-PCR targeting RNA-dependent RNA polymerase and E genes. Virus isolation from positive samples was attempted in vitro on Vero E6 cells. RESULTS: Twenty-six samples were collected and only two were positive for low-level SARS-CoV-2 RNA, both collected on the external surface of continuous positive airway pressure helmets. All transport media were inoculated onto susceptible cells, but none induced a cytopathic effect on day 7 of culture. CONCLUSIONS: Even though daily contact with inanimate surfaces and patient fomites in contaminated areas may be a medium of infection, our data obtained in real-life conditions suggest that it might be less extensive than hitherto recognized.

Ultrasonography in ulnar neuropathy at the elbow: relationships to clinical and electrophysiological findings.

INTRODUCTION: Though ultrasonography (US) is commonly used in the diagnosis of carpal tunnel syndrome (CTS), there are only few studies on the utility of US in ulnar neuropathy at the elbow (UNE). The aims of this study were to measure the cross-sectional area (CSA) of the ulnar nerve at the elbow and to correlate CSA values with clinical and electrophysiological findings. PATIENTS AND METHODS: Thirty-three UNE patients (mean age 50.1 years) were consecutively enrolled. Diagnosis was based on clinical findings and slowing of the motor conduction velocity (MCV) of the ulnar nerve across the elbow. CSAs of the ulnar nerve were measured within the cubital tunnel at the level of the medial epicondyle (CSA-M) and approximately 2cm proximal to this point (CSA-I). Correlations between CSA and demographic, clinical (ordinal severity scale and self-administered symptom questionnaire), and electrophysiological findings (neurographic results and ordinal electrophysiological severity scale) were calculated using Spearman's correlation coefficient. RESULTS: The mean CSA-M and CSA-I were 9.6+/-8.5 and 9.3+/-5.6mm2, respectively. Fifteen (45.5%) and eight (24.5%) cases showed abnormal CSA-M and CSA-I values, respectively (mean+2S.D. compared to a control group of the same age). All cases with abnormal CSA-I had abnormal CSA-M except one. Significant relationships were only found between CSA-M and CSA-I with across elbow MCV, sensory action potential amplitude, and the electrophysiological severity scale score. DISCUSSION: Our study showed anomalous CSA values in less than 50% of the UNE cases. This is less than the reported percentages in the few literature reports. This difference may be due to our enrolment criteria or to the electrophysiological and US techniques. It is likely that the CSAs measured by axial scan at a fixed level of the cubital tunnel may have lower diagnostic sensitivity than the same technique used in CTS.

Long term follow-up of carpal tunnel syndrome during pregnancy: a cohort study and review of the literature.

INTRODUCTION: Carpal tunnel syndrome (CTS) occurring during pregnancy is considered to have a short and benign course and very few cases required surgery, however there is no information in literature on long term follow-up. The aim of this study was a systematic review of the literature and to report 3-year follow-up after delivery in a sample of pregnant women with CTS. PATIENTS AND METHODS: We enrolled 45 consecutive pregnant women with CTS (mean age 32 years). Diagnosis was based on clinical and neurographic findings. Clinical and electrophysiological severity of CTS were scored according to an ordinal scale and the self-administered Boston questionnaires on symptoms (BQ-SYMPT) and functional status (BQ-FUNCT) of the hand during pregnancy and one-year after delivery. Symptoms were evaluated again by BQ over the telephone three years after delivery. RESULTS: At one-year follow-up BQ-SYMPT and BQ-FUNCT scores improved in 40% of women, did not change in 46.7% and 55.6% and worsened in 13.3% and 4.4%, respectively. Clinical severity was stage 0 (i. e. without symptoms) in 26.7% of women, improved in 6.7%, unchanged in 60% and worse in 6.7%. Electrophysiological severity was stage 0 (i.e. no delay in median nerve conduction) in 17.8%, improved in 20%, unchanged in 57.8% and worse in 4.4%. Only one woman underwent surgery (5 months after delivery), three were treated with local steroid injection before delivery and 18 used a splint, 8 of whom continued to do so periodically after one year. At 3-year follow-up 51% were symptom-free and 49% had anomalous ( > 1) BQ scores, but mean BQ scores improved with respect to those at baseline and one-year follow-up. CONCLUSION: A Pubmed search identified 20 papers in which therapy and follow-up could be deduced. Almost all reported a short follow-up with disappearance of symptoms. Our study confirms that pregnancy-related CTS has a benign course: improvement of symptoms was evident at one- and 3-year follow-up, but about half the women still complained of symptoms 3 years after delivery. Only one woman underwent surgery and 11% still sometimes wore a splint at night. Despite improvement of symptoms, distal sensory conduction velocity of the median nerve improved but remained delayed in 84% of women one year after delivery.

Reappraisal of the F/M amplitude ratio in carpal tunnel syndrome.

The F-wave/M-wave amplitude (F/M-amp) ratio has been shown to be increased in peripheral neuropathies, provided the maximum M-wave is relatively preserved. Reduced M-wave amplitudes and central facilitation of antidromically-induced reactivation of the anterior horn cells' axon hillocks (F-wave) are believed to contribute to higher F/M-amp ratios. The present study was undertaken to re-evaluate mechanisms responsible for higher F/M-amp ratios in carpal tunnel syndrome (CTS). We enrolled 232 cases affected by CTS and 108 controls. Fand M-wave amplitudes and F-wave chronodispersion were analyzed for the median and ulnar nerves. The F/M-amp ratio of the median nerve in CTS subjects with moderate-severe nerve damage was significantly higher than that of mild CTS subjects and controls. Chronodispersion of the median nerve F-wave increased with increasing CTS severity. We conclude that the relative preservation of the median nerve F-wave is due to damage to the large diameter muscle afferent fibers responsible for the monosynaptic response. Absence of the monosynaptic response makes the small motoneurons, usually inaccessible to the antidromic volley because of its collision with the orthodromic reflex volley, able to fire in the F-wave.

Changes in motor axon recruitment in the median nerve in mild carpal tunnel syndrome.

OBJECTIVE: To determine whether patients with mild carpal tunnel syndrome (CTS) and conventional electrodiagnostic evidence of selective involvement of sensory conduction show changes in motor axon recruitment in the median nerve. METHODS: Wrist-to-abductor pollicis brevis (APB) motor axon conduction was studied by analysing the relationship between the intensity of electrical stimulation and the size of motor response (input-output curve) in 30 CTS patients with conventional electrodiagnostic evidence of selective involvement of sensory conduction. Parameters (threshold, slope and plateau) of input-output curves were compared with those obtained in 30 controls. RESULTS: The slope of the input-output curve of CTS patients was less steep than that of controls. For stimulus intensity above M-wave threshold (MTh), fewer motor axons were recruited in patients than controls. CONCLUSIONS: Motor fibres are affected in CTS when conventional electrodiagnostic tests show normal motor conduction. Altered recruitment of motor axons could mainly be due to impairment of energy-dependent processes which affect temporal dispersion of the compound volley or axonal conduction block. SIGNIFICANCE: In mild CTS, motor fibres are more often affected than was originally thought. The sensitivity of wrist-to-APB motor conduction studies may be increased by using submaximal stimulus intensities.

Carpal tunnel syndrome and ulnar neuropathy at the elbow in floor cleaners.

OBJECTIVE: To determine the occurrence of carpal tunnel syndrome (CTS) and ulnar neuropathy at the elbow (UNE) in a cohort of floor cleaners and to check differences between workers with and without CTS. METHODS: All female floor cleaners of three major hospitals in Tuscany (Italy) were contacted. Clinical and electrophysiological severity of CTS and UNE were evaluated with standardized scales and symptoms were assessed with the self-administered Boston Questionnaire (BQ); demographic and non-occupational factors and durations of current and previous occupations were recorded. Univariate analysis of risk factors was performed in workers with and without CTS. Logistic regression was used to evaluate the capacity of independent variables to predict CTS. RESULTS: Out of a total of 179 cleaners, 145 (81%)-mean age 39.6 years (20-64 years)-were enrolled in the study; 70 (48%) had CTS (diagnosis based on clinical and electrophysiological findings). BQ symptom and hand function scores were anomalous in 108 (74%) and 84 (58%) subjects, respectively. UNE was detected in 7/103 women. Univariate analysis showed that cleaners with CTS were older, had greater BMI and longer exposure to cleaning with previous employers than those without CTS. In the logistic regression, the only predictor of CTS was cleaning with previous employers (O.R. 12.1, 95% CI 3-49.9). CONCLUSIONS: These results indicate a high occurrence of CTS in floor cleaners; UNE is less frequent than CTS, presumably due to repetitive movements that stress wrists more than elbows. The only predictive factor of CTS was cleaning as an occupation with previous employers. Therefore, the actual risk factor for CTS could not be cleaning per se, but how this job is performed.

Multicenter study on carpal tunnel syndrome and pregnancy incidence and natural course.

OBJECTIVE: To evaluate the incidence of carpal tunnel syndrome (CTS) in pregnancy through a validated and multiperspective assessment of CTS and to assess the course of carpal tunnel syndrome after pregnancy. METHODS: During 2000-2001, the Italian CTS study group in 7 Italian centers studied the occurrence of CTS in women during the last period of pregnancy. The group enrolled and followed-up (10-15 months) 63 women during and after pregnancy with multiple measurements of CTS. In addition to the physician-centered and neurophysiologic traditional evaluations, a validated patient-oriented measurement to obtain more comprehensive and consistent data for severity of symptoms and functional impairment was adopted. RESULTS: CTS was clinically diagnosed in more than half of women (62%). Neurophysiological evaluation provided diagnosis of CTS in around half of women (43% were positive in one hand at least). Comparison of baseline and follow-up data showed a significant spontaneous improvement of patient-oriented and neurophysiologic measurements. Nevertheless, about half of women with CTS during pregnancy still complained of CTS symptoms one year after delivery. CONCLUSIONS: Our observations confirmed the frequent occurrence of CTS in pregnancy. At follow-up we observed that most CTS cases improve spontaneously without treatment but only in half of women CTS symptoms disappeared one year after delivery.

Italian multicentre study of peroneal mononeuropathy at the fibular head: study design and preliminary results.

BACKGROUND: The most common entrapment in the lower extremity is peroneal mononeuropathy (PM) at the fibular head. Several studies of this condition have been published but, until now, no wide multicenter clinical-neurophysiological studies on PM are available. In recent years, multicenter studies have been suggested; moreover it is commonly accepted that a multiperspective approach provides more comprehensive results. METHOD: The Italian CTS and other entrapments Study Group has designed a strict clinical and neurophysiological protocol to carry out a wide multicentre study on PM at the fibular head. In addition to traditional clinical-neurophysiological evaluation, the group has also adopted validated disability and patient-oriented measurements in order to obtain more comprehensive and reliable data about this entrapment. The study was designed: 1) to identify predisposing factors; 2) to better assess the clinical picture; 3) to evaluate relationships between etiological, clinical and neurophysiological findings; 4) to evaluate the natural evolution of the entrapment. Study design is described. FINDINGS: During the period from November 2002 to January 2004, 69 patients were enrolled consecutively in eleven Italian centres. Our preliminary data show that PM involves men more frequently than women (M:F = 3.9:1). With regard to the predisposing factors, PM is idiopathic (16%) or due to surgery (21.7%), prolonged posture (23.2%), weight loss (14.5%), external compression (5.8%), arthrogenic cyst at the fibula (1.4%), trauma (10.1%); it also occurred in bedridden patients (7.3%). Unexpectedly, peroneal nerve lesions were due not only to surgical operation close to the peroneal region, but were also associated with thoracic-abdominal surgery. Usually PM involves both terminal branches; patients complain of motor deficit in 99.5% of cases, sensory symptoms in 87.9% and pain in 19.7%. CONCLUSIONS: Our preliminary results provide some interesting information and confirm the usefulness of multicentre and multiperspective studies to standardise the approach to nerve entrapment.

Mimotopes of the hyper variable region 1 of the hepatitis C virus induce cross-reactive antibodies directed against discontinuous epitopes.

Hepatitis C virus (HCV) is a major cause worldwide of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma, and the development of an effective vaccine represents a high priority goal. The hyper variable region 1 (HVR1) of the second envelope protein (E2) of HCV contains a principal neutralizing determinant, but it is highly variable among different isolates and it is involved in the escape from host immune response. To be effective, a vaccine should elicit a cross-reacting humoral response against the majority of viral variants. We show that it is possible to achieve a broadly cross-reactive immune response in rabbits by immunization with mimotopes of the HVR1, selected from a specialized phage library using HCV patients' sera. Some of the cross-reacting anti-mimotope antibodies elicited in rabbits, recognize discontinuous epitopes in a manner similar to those induced by the virus in infected patients.

Differences in the availability of diagnostics and treatment modalities for chronic hepatitis B across Europe.

The prevalence and management of chronic hepatitis B virus (HBV) infection differ among European countries. The availability and reimbursement of diagnostics and drugs may also vary, determining distinct treatment outcomes. Herein, we analyse differences in medical facilities for the care of patients with chronic HBV infection across Europe. A survey was sent to the members of the ESCMID Study Group for Viral Hepatitis, all of whom are experts in chronic HBV infection management. The comprehensive survey asked questions regarding hepatitis B surface antigen (HBsAg) prevalence, the availability of diagnostics and drugs marketed, and distinct clinical practice behaviours in the management of chronic HBV infection. World Bank data were used to assess the economic status of the countries. With 16 expert physicians responding (69%), the HBsAg prevalence rates were <1% in France, Hungary, Italy, The Netherlands, Portugal, Spain, and the UK, intermediate (1-5%) in Turkey, Romania, and Serbia, and high (>5%) in Albania and Iran. Regarding the availability and reimbursement of HBV diagnostics (HBV DNA and liver stiffness measurement), HBV drugs (interferon, lamivudine, tenofovir, and entecavir), HBV prophylaxis, and duration of HBeAg-positive and HBeAg-negative HBV infection, the majority of high-income and middle-income countries had no restrictions; Albania, Iran and Serbia had several restrictions in diagnostics and HBV drugs. The countries in the high-income group were also the ones with no restrictions in medical facilities, whereas the upper-middle-income countries had some restrictions. The prevalence of chronic HBV infection is much higher in southern and eastern than in western European countries. Despite the availability of European guidelines, policies for diagnostics and treatment vary significantly across European countries.

A human antibody specific for hepatitis C virus core protein: synthesis in a bacterial system and characterization.

The cDNA coding for the Fab fragment of the human B12.F8 antibody (Ab), directed against the putative nucleocapsid component (core protein) of hepatitis C virus (HCV), was cloned in the prokaryotic phagemid vector, pHEN-1, to obtain its expression in Escherichia coli. The functionality and specificity of the recombinant Ab, called B12Fab, were examined by Western blot and ELISA using recombinant HCV core protein as antigen. The specificity of B12Fab was further confirmed by ELISA with the 33-mer peptide epitope recognized by the original whole B12.F8 Ab. By immunofluorescence, the recombinant B12Fab was shown to recognize HCV core protein produced in cells transfected with HCV cDNA, indicating that the recombinant B12Fab is suitable as a diagnostic tool for tissue localization of the virus. The B12Fab also functioned when displayed on phage particles, providing the basis for future experiments of in vitro affinity maturation and selection of mutants. The variable chain coding regions of the recombinant B12Fab clone were sequenced and the V-gene usage was determined by comparison with the V kappa and VH germline sequences. The B12Fab V kappa chain belongs to the subgroup II and shows the highest degree of homology with the A3 germline gene, whereas the sequence of the VH chain is strictly related to that of the Humhv3019b18 gene of the VH3 family. These results are, to our knowledge, the first report of molecular cloning and characterization of a functional human Ab specific for an HCV antigen.

Evoked potentials in cerebrotendinous xanthomatosis and effect induced by chenodeoxycholic acid.

Evoked potentials are reported in 10 patients with cerebrotendinous xanthomatosis, eight of whom had peripheral neuropathy. Four subjects showed delayed N13 to N20 interpeak latencies for arm somatosensory evoked potentials, and five showed moderately prolonged I to III and I to V interpeak latencies of brain-stem auditory evoked potentials. Six of seven patients showed marked delay and desynchronization of visual evoked potentials. All five patients undergoing transcutaneous magnetic stimulation of the motor cortex presented greatly delayed central motor conduction time, especially of the lower limbs. After treatment with chenodiol (750 mg/d for at least 2 years), there was a significant improvement in nerve conduction velocities, N13 to N20 interpeak latencies, and visual evoked potential latencies. Brain-stem auditory evoked potentials remained unchanged.

Carpal tunnel syndrome in pregnancy: multiperspective follow-up of untreated cases.

In a follow-up of carpal tunnel syndrome (CTS) after pregnancy, the Italian CTS Study Group prospectively studied 63 pregnant women with multiple measurements of CTS symptoms. Fifty-four percent of women with CTS symptoms during pregnancy had symptoms 1 year later. Patients with onset of CTS symptoms early during pregnancy are less likely to improve after delivery.