Use of optical coherence tomography for the diagnosis of preclinical lesions of circumscribed palmar hypokeratosis.

Circumscribed hypokeratosis of palms and soles is a rare dermatosis, usually affecting women. Diagnosis is mainly based on the clinical characteristics, including the clinical appearance and anatomical site of the skin lesions and on the demographic features of the affected patients, usually middle-aged to elderly women. Skin biopsy may be performed to confirm clinical diagnosis. Optical coherence tomography (OCT) is a technique that has been undergone substantial development in dermatology in recent years, and its use in clinical practice has been growing progressively. Several dermatological conditions have been studied with this tool, but to our knowledge, it has not been used to investigate this form of hypokeratosis. We report a case of circumscribed palmar hypokeratosis for which diagnosis was confirmed by OCT, which was performed as the patient was reluctant to undergo skin biopsy because of its invasiveness. We highlight the potential use of OCT in obtaining a virtual skin biopsy to confirm clinical diagnosis and identify preclinical skin lesions amenable to early treatment.

Non-enzymatic glycosylation of a type I collagen matrix: effects on osteoblastic development and oxidative stress.

BACKGROUND: The tissue accumulation of protein-bound advanced glycation endproducts (AGE) may be involved in the etiology of diabetic chronic complications, including osteopenia. The aim of this study was to investigate the effect of an AGE-modified type I collagen substratum on the adhesion, spreading, proliferation and differentiation of rat osteosarcoma UMR106 and mouse non-transformed MC3T3E1 osteoblastic cells. We also studied the role of reactive oxygen species (ROS) and nitric oxide synthase (NOS) expression on these AGE-collagen mediated effects. RESULTS: AGE-collagen decreased the adhesion of UMR106 cells, but had no effect on the attachment of MC3T3E1 cells. In the UMR106 cell line, AGE-collagen also inhibited cellular proliferation, spreading and alkaline phosphatase (ALP) activity. In preosteoblastic MC3T3E1 cells (24-hour culture), proliferation and spreading were significantly increased by AGE-collagen. After one week of culture (differentiated MC3T3E1 osteoblasts) AGE-collagen inhibited ALP activity, but had no effect on cell number. In mineralizing MC3T3E1 cells (3-week culture) AGE-collagen induced a decrease in the number of surviving cells and of extracellular nodules of mineralization, without modifying their ALP activity. Intracellular ROS production, measured after a 48-hour culture, was decreased by AGE-collagen in MC3T3E1 cells, but was increased by AGE-collagen in UMR106 cells. After a 24-hour culture, AGE-collagen increased the expression of endothelial and inducible NOS, in both osteoblastic cell lines. CONCLUSIONS: These results suggest that the accumulation of AGE on bone extracellular matrix could regulate the proliferation and differentiation of osteoblastic cells. These effects appear to depend on the stage of osteoblastic development, and possibly involve the modulation of NOS expression and intracellular ROS pathways.

Ultrasound-guided percutaneous ethanol injection under general anesthesia for the treatment of hepatocellular carcinoma on cirrhosis: long-term results in 268 patients.

OBJECTIVE: Percutaneous ethanol injection (PEI) under general anesthesia (One-shot PEI) is a therapy for large and multiple hepatocellular carcinoma (HCC) by the injection of a large amount of ethanol into the tumor. We report our results with 5-year survival rates in patients with HCC on cirrhosis treated with One-shot PEI. PATIENTS AND METHODS: From October 1992 to March 1998, 268 cirrhotic patients (age 42-82 years; 191 males; 95 Child-Pugh's A class, 150 B and 23 C class of cirrhosis) with 515 HCC nodules underwent One-shot PEI. Diameter of HCC nodules ranged from 0.6 to 14 cm (mean 5.02 +/- 2.2 cm; median: 4 cm). One hundred and thirty-eight patients had a single nodule (range 3.2-14 cm; mean 5.6 +/- 2.1 cm), 130 had multiple nodules, up to six nodules (mean 2.9 nodules) (range 0.6-11 cm; mean 4.8 +/- 2.1 cm) RESULTS: CT showed complete necrosis in 357/506 nodules (70%). Five patients (1.8%) with nine nodules died as a result of the procedure (variceal bleeding in three cases, liver failure in one and hemoperitoneum in one). The overall survival rates were 93, 83, 74, 65 and 59% at 1, 2, 3, 4 and 5 years, respectively. Survival rates were 90, 84, 82 and 82% at 12, 24, 36 and 48 months, respectively, in patients with a single nodule less than or = 5 cm, and 97, 71, 59, 59 and 59% at 12, 24, 36, 48 and 60 months, respectively, in patients with single nodule >5 cm. Patients with multiple nodules had survival rates of 97, 89, 75, 60 and 60% at 12, 24, 36, 48 and 60 months, respectively. CONCLUSION: PEI of large and multiple HCC showed survivals similar to conventional PEI for patients with smaller tumors.

Vanadate-induced nitric oxide production: role in osteoblast growth and differentiation.

Nitric oxide (NO) has been shown to act as a mediator of cytokines in bone tissue. We have previously demonstrated that vanadium compounds are insulin- and growth factor-mimetic compounds in osteoblasts in culture, although high doses are toxic to these cells. In this study, we measured NO production in two osteoblast-like cells (UMR106 and MC3T3E1) incubated with different concentrations (2.5-100 microM) of vanadate. Vanadate induced NO release in a biphasic manner, with levels being significantly increased at concentrations over 50 microM. The NO donor, sodium nitroprusside, mimicked the vanadate effect: it inhibited cell growth and alkaline phosphatase activity in a dose-dependent manner. Vanadate enhanced the NO synthases, the endothelial and inducible (eNOS and iNOS) isoforms, in a dose-dependent manner. Experiments performed with the ionophore A23187 and EGTA suggested that vanadate-induced NO production involves Ca(2+)-dependent and -independent mechanisms. Altogether, our results suggest that NO may play a critical role in the bioactivity of vanadium in osteoblast-like cells.

Protective immunity against murine hepatitis virus (MHV) induced by intranasal or subcutaneous administration of hybrids of tobacco mosaic virus that carries an MHV epitope.

Hybrids of tobacco mosaic virus (TMV) were constructed with the use of fusion to the coat protein peptides of 10 or 15 amino acids, containing the 5B19 epitope from the spike protein of murine hepatitis virus (MHV) and giving rise to TMV-5B19 and TMV-5B19L, respectively. The TMV hybrids were propagated in tobacco plants, and the virus particles were purified. Immunogold labeling, with the use of the monoclonal MAb5B19 antibody, showed specific decoration of hybrid TMV particles, confirming the expression and display of the MHV epitope on the surface of the TMV. Mice were immunized with purified hybrid viruses after several regimens of immunization. Mice that received TMV-5B19L intranasally developed serum IgG and IgA specific for the 5B19 epitope and for the TMV coat protein. Hybrid TMV-5B19, administered by subcutaneous injections, elicited high titers of serum IgG that was specific for the 5B19 epitope and for coat protein, but IgA that was specific against 5B19 was not observed. Mice that were immunized with hybrid virus by subcutaneous or intranasal routes of administration survived challenge with a lethal dose (10 x LD50) of MHV strain JHM, whereas mice administered wild-type TMV died 10 d post challenge. Furthermore, there was a positive correlation between the dose of administered immunogen and protection against MHV infection. These studies show that TMV can be an effective vaccine delivery vehicle for parenteral and mucosal immunization and for protection from challenge with viral infection.

Efficacy of hepatitis A vaccine in prevention of secondary hepatitis A infection: a randomised trial.

BACKGROUND: Hepatitis A vaccination stops outbreaks of hepatitis A infection, but its efficacy against infection after exposure has not been proven. We investigated the use of hepatitis A vaccine to prevent secondary infections with hepatitis A virus (HAV). METHODS: We did a randomised controlled trial of hepatitis A vaccine in household contacts of people with sporadic HAV infection (index cases). Households (index cases and contacts) were randomly assigned to the vaccine group or unvaccinated group, according to the study week in which they were enrolled. All household contacts in the vaccine group received vaccination at the time of entry to the study. FINDINGS: During 45 days of follow-up, secondary infection had occurred in ten (13.3%) of 75 households (two families had two cases each) in the untreated group and in two (2.8%) of 71 households in the vaccine group. The protective efficacy of the vaccine was 79% (95% CI 7-95). The number of secondary infections among household contacts was 12 (5.8%) of 207 in the unvaccinated group and two (1.0%) of 197 in the vaccinated group. Therefore, 18 individuals needed to be vaccinated to prevent one secondary infection. INTERPRETATION: Hepatitis A vaccine is effective in the prevention of secondary infection of HAV and should be recommended for household contacts of primary cases of HAV infection.

Correlation between virus genotype and chronicity rate in acute hepatitis C.

BACKGROUND/AIMS: Forty-two patients with the diagnosis of acute hepatitis C virus hepatitis were studied to investigate the relationship between hepatitis C virus genotype and progression to chronic infection. METHODS: The patients were followed for more than 1 year (mean age 29 years, male/female ratio 2.5). Intravenous drug use was documented in 15 cases, blood transfusion in four, surgical intervention, dental therapy or other parenteral exposure in 15, and unknown factors in the remaining eight. The evolution to chronicity was diagnosed on the basis of a persistent increase in transaminase levels, the presence of HCV-RNA and the histological pattern of chronic hepatitis. RESULTS: The majority of cases presented hepatitis C virus infection of subtype 1a (38.1%) or 1b (33.9%). Six cases showed the presence of genotype 3a (14.3%). Subtype 2c was observed in three out of four cases infected with genotype 2. No significant association was demonstrated with documented risk factors. The overall chronicity rate was 59.5%. This value increased to 92% in individuals infected with genotype 1b. By multivariate analysis the age-adjusted odds ratio for infection with genotype 1b as compared with all other genotypes was 14.4 (95% confidence interval; 1.52-137). Moreover, significant differences (p= 0.0002) were present in this group for histological activity index (8.7 as compared with 5-7). CONCLUSIONS: The results of this prospective study are consistent with an independent association between hepatitis C virus genotype 1b and a poor prognosis.

Morphologic and motility changes of the gallbladder in response to acute liver injury. A prospective real-time sonographic study in 255 patients with acute viral hepatitis.

In 255 patients with acute viral hepatitis and in 50 healthy controls, wall thickness, volume, and percentage of maximal contraction of the gallbladder were prospectively evaluated using real-time ultrasonography. A hypotonic, hypokinetic gallbladder was shown in 58.4% of the cases, expressed by normal parietal thickness, larger volume, and lower response to fat stimulation than the controls. In the remaining patients, wall thickening, decreased volume, and reduced contraction were compatible with a hypertonic gallbladder. Because the latter pattern was never observed in patients with disease onset dating back more than 9 days, it is conceivable that gallbladder hypertonicity in the early phase of the illness is followed by depression of tone and motor activity. However, such sonographic features turned out to be short-lived and reversible as they disappeared in all patients within 3 weeks of the first ultrasound examination. Moreover, none of the sonographic abnormalities correlated with either biochemical indices of acute disease or the patients' long-term outcomes.

Ultrasonically-guided percutaneous transcholecystic cholangiography--an alternative approach in cases of biliary obstruction and failure of percutaneous transhepatic cholangiography.

Fourteen ultrasonically-guided percutaneous transcholecystic cholangiographies (PTCC) were performed in subjects with biliary obstruction with different underlying diseases. No complication was observed, and the procedure permitted diagnosis in all cases, although the previously reported difficulty of visualizing proximal bile ducts was confirmed in two cases. PTCC can constitute a valid and safe diagnostic alternative in obstructive jaundice in which no dilation of intrahepatic bile ducts is revealed on US, in cases in which percutaneous trans-hepatic cholangiography fails.

Echo-guided percutaneous puncture: a safe and valuable therapeutic tool for amebic liver abscess.

To clarify the therapeutic role of echo-guided percutaneous puncture (EPP) in management of amebic liver abscess, 20 patients (24 abscesses) received metronidazole plus EPP. Fluid was aspirated through Chiba needles under real-time sonographic guidance so as to reduce cavity size to less than 3 cm. Not more than two EPPs were necessary in the majority of cases and no complication followed the procedure. This scheme resulted in a shortening of time of both hospitalization (less than or equal to 20 days) and liver lesion healing as assessed by ultrasound (less than or equal to 4 months). It is concluded that EPP is a valuable and safe therapeutic tool for hepatic amebic abscess.

[Clinical significance of hyperechogenic focal lesions of the cirrhotic liver]. / Significato clinico delle lesioni focali iperecogene nel fegato cirrotico.

A review was made of the ultrasonographic (US) examinations performed over the period 1981-1986; 27 cirrhotic patients with hyperechoic liver lesions were identified, whose diagnoses had been made by means of either US-guided percutaneous biopsy, or laparoscopy, or autopsy. In 24 patients hepatocellular carcinomas nodules (HCC) were found, associated with cirrhosis, while in 3 cases only cirrhosis was seen. In the above mentioned 3 cases, a 2-year US follow-up showed no variation in the size of the nodules. These data confirm the importance of US in the screening of risk HCC patients, and point out that--however small--hyperechoic lesions in a cirrhotic liver suggest the cancerization of the substanding cirrhosis.

[Chlamydia trachomatis genital infections and contraception]. / Infezioni genitali da Chlamydia trachomatis e contraccezione.

PIP: 330 women with a median age of 30.15 (+- 9.5) years sought gynecological consultation for advice on contraception and for cervical carcinoma screening. Anamnesis explored the presence of dysuria, dyspareunia, secretions, and pelvic pain, the number of partners, and type of contraceptive used. Endocervical samples were collected by means of tampon and the specimens were analyzed for 48 to 120 hours to find antigens of Chlamydia trachomatis (C.T.) by a solid phase immunoenzymatic test. Peripheral blood samples were also taken from all women to look for antibodies of C.T. and also the indirect immunoperoxidase test was used to search for specific antibodies of C.T. (IgM, IgA, IgE, IgG). The chi-square test was applied for statistical analysis. None of the women who used oral hormonal contraceptives or condoms were infected (presence of antigens and positivity for IgM and/or IgE and/or IgA), however, 36 of 90 IUD users (40%) were infected, 18 of 132 women who used no contraceptives whatsoever (13.7%) were also infected. 91% of the subjects had a single partner. In view of these findings the use of the condom and oral contraceptives is recommended with proper instruction about their potential side effects.^ieng

Survey of delta infection in the Naples basin: a possible epidemiologic model for endemic areas.

The prevalences of delta co-infections and superinfections in 100 randomly selected subjects for each year from 1977 to 1982 and in all the subjects of subsequent years until April 1986, admitted to our Department with acute viral hepatitis B (AVHB), were evaluated and compared with the annual incidence of cases of AVHB reported in Naples during the same period. Moreover, anti-delta antibodies were determined in the sera of 25 consecutive cases of HBsAg-positive chronic active hepatitis and 25 consecutive cases of HBsAg-positive chronic active hepatitis and 25 consecutive cases of HBsAg-positive cirrhosis, respectively, for 1977, 1980, 1983 and 1986. Our data show a high, constant circulation of HDV and a decrease in its incidence in acute forms over the last 3 years, which coincides with the parallel lower incidence of AVHB, but which is not reflected in the delta prevalence in the chronic forms. They also indicate the possible existence of alternate cycles of increase and decrease in the infection, partly dissociated from HBV circulation, which present peculiar epidemiologic characteristics.

A histological study of hepatitis delta virus liver disease.

The histopathology of hepatitis delta virus disease was studied in carriers of HBsAg with chronic hepatitis delta antigen-positive hepatitis and in serial biopsies of patients with acute hepatitis delta virus hepatitis that progressed to chronicity. There was no histologic feature distinctive of hepatitis delta virus from other types of viral hepatitis. Biopsy specimens of patients with chronic disease exhibited portal and periportal inflammation with piecemeal necrosis, conforming to a picture of aggressive hepatitis often accompanied by cirrhosis. Characteristic was a marked intralobular infiltration by mononuclear cells and a degenerative eosinophilic change of the hepatocytic cytoplasms conducive to the formation of acidophilic bodies. Liver specimens from patients with hepatitis delta virus hepatitis exhibited aspects of focal, confluent and bridging necrosis. The disease progressed to chronicity irrespective of the original histological features. The expression of intrahepatic hepatitis delta antigen was reduced in the phase of the acute hepatitis but increased in parallel with the development of chronic active liver disease. In late-stage cirrhosis, expression of hepatitis delta antigen was usually low.

Cirrhosis: value of caudate to right lobe ratio in diagnosis with US.

To verify the value of ultrasound (US) in the diagnosis of cirrhosis, the ratio of transverse caudate lobe width to right lobe width (C/RL) was determined with US in 25 healthy subjects and 156 consecutive patients with either histologically proved acute viral, chronic persistent, or chronic active hepatitis or cirrhosis. The C/RL ratio had a sensitivity of 43%, a specificity of 100%, and an accuracy of 79% in cirrhosis. The sensitivity was very low in alcoholic cirrhosis, low in cryptogenic cirrhosis, and high in hepatitis B virus related cirrhosis. In spite of its fairly low overall sensitivity, the C/RL ratio is a useful measurement in assessing chronic liver disease because of its high specificity in cirrhosis.

Ultrasound evaluation of uncomplicated and complicated acute viral hepatitis.

Seven hundred ninety-one consecutive patients with acute viral hepatitis, 17 of whom had liver failure, and 97 healthy volunteers were examined by ultrasound. No specific patterns were found in either the uncomplicated or the complicated forms. Only 19 subjects showed a typical "bright liver" pattern, which is correlated with significant vacuolar hepatocellular degeneration. The increased brightness and clear visualization of portal vein radicle walls, previously described in this disease, were detected in only 32.2% of the hepatitis patients but were also seen in 30.9% of the normal controls.