Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon treated and untreated patients: a long term cohort study

BACKGROUND/AIMS: We studied the influence of biochemical and virologic patterns and interferon on the outcome of anti-HBe positive chronic hepatitis B in 164 (103 treated) consecutive patients, followed-up prospectively for a mean of 6 years (21 months-12 years). METHODS: Histology, biochemical and virologic profiles were characterized by monthly monitoring during the first 12 months of follow-up. Thereafter patients underwent blood and clinical controls every 4 and 6 months, respectively. Cirrhosis at follow-up histology or end stage complications of cirrhosis served as end points for the analysis of factors influencing disease progression in patients with baseline chronic hepatitis or cirrhosis, respectively. RESULTS: Disease progression was associated with older age (P<0.001), absence of previous HBeAg history (P=0.017) and higher serum HBV-DNA levels (P=0.009) (more frequently observed in unremitting disease profile, P=0.012) at multivariate analysis. Fluctuations of IgM anti-HBc levels (associated with disease exacerbations, P=0.045) correlated with end stage complications in cirrhotics (P=0.011). Disease improved in 14.6 and 1.6% of treated and untreated patients, respectively (P=0.015): interferon slowed disease progression (P<0.001). CONCLUSIONS: The outcome of anti-HBe positive chronic hepatitis B is worsened by older age and persistent viral replication or hepatitis exacerbations in chronic hepatitis or in cirrhotic patients, respectively. Interferon reduces by 2.5-folds disease progression.     

Juvenile chronic arthritis and imaging: comparison of different techniques

OBJECTIVE: The aim of this study was to compare imaging findings obtained with different techniques in a patient with juvenile chronic arthritis. METHODS: The patient was a 12 years-old child with a 7-months history of arthritis of the first metatarsophalangeal joint of the right foot. The involved area was explored with the following imaging techniques: X-ray, technetium bone scintigraphy, magnetic resonance, gray-scale and power-Doppler ultrasonography. RESULTS: No abnormalities were detected with conventional X-ray. Scintigraphy showed an abnormal uptake of the radionuclide in the first metatarsophalangeal joint of the right foot. Magnetic resonance without contrast revealed clearly evident features of an active process of synovitis. Ultrasonography was able to detect the presence of joint effusion, synovial proliferation, bone erosion of the first metatarsal head. Power-Doppler examination revealed evident signs of soft tissue hyperaemia. CONCLUSIONS: Comparative assessment of different imaging techniques in this patient with recent-onset juvenile chronic arthritis indicates that high resolution ultrasonography provides the most detailed evaluation of the joint involvement with respect to the other imaging techniques.     

Intralesional therapy in carpal tunnel syndrome: a sonographic-guided approach

OBJECTIVE: The aim of this pictorial essay is to show a representative example of sonographic-guided injection in carpal tunnel syndrome associated with tenosynovitis of the finger flexor tendons. METHODS: Images were obtained using a real-time ultrasound system (AU4-idea; Esaote Biomedica, Genoa, Italy) equipped with a 13-MHz linear transducer. The best injection site was detected using a fine metal clip placed between the skin and the transducer. The images here were obtained in a patient with rheumatoid arthritis and carpal tunnel syndrome secondary to tenosynovitis of the finger flexor tendons. RESULTS: Steroid injection within the carpal tunnel under sonographic control was easily performed. All steps of the needle placement within the widened tendon sheath were carefully evaluated on the monitor screen. Marked clinical improvement occurred shortly thereafter (3 days) and increased over the next 6 weeks. CONCLUSION: A detailed assessment of the carpal tunnel and a correct, safe placement of the needle for steroid injection can be quickly performed under sonographic guidance.     

Effect of plasma metformin concentrations on serum lipid levels in type II diabetic patients

Summary In this study we evaluated the relationships between plasma metformin levels, measured by reversed-phase high-performance liquid chromatography, and serum lipid levels in 20 metformintreated, type II diabetic patients. Mean fasting plasma metformin concentration was 490 ± 188 ng/ml. No correlation was found between daily dose of drug and lipid parameters. A significant correlation emerged between circulating metformin concentration and serum triglycerides (r=−0.574, p<0.01), HDL-cholesterol (r=0.583, p<0.01) and HDL₂-cholesterol (r=0.670, p<0.05). Multiple linear regression analysis showed that the correlation between plasma metformin concentration and serum triglycerides still remained significant after correction for other clinical and metabolic parameters. Total cholesterol and HDL₃-cholesterol were not correlated with metformin concentrations. These results demonstrate the clinical usefulness of measuring plasma metforminc concentrations and indicate that some effects of metformin on lipid metabolism depend on the drug plasma levels.     

Phagocytosis of Hemozoin (Native and Synthetic Malaria Pigment), and Plasmodium falciparum Intraerythrocyte-Stage Parasites by Human and Mouse Phagocytes

Hemozoin, the detoxification product of hemoglobin heme, piles up as electron-dense material in the food vacuole (FV) of intraerythrocytic malaria parasites (malaria pigment). In infected individuals, pigment is internalized by both circulating and resident phagocytes, thus modulating their functions. Synthetic beta-hematin, prepared in vitro from hematin (ferriprotoporphyrin IX hydroxide) in acidic condition, is spectroscopically identical to hemozoin. In this electron microscopy study, native and synthetic hemozoin also prove to be morphologically indistinguishable (large polygonal crystals with apparent transverse banding) and to undergo the same process when internalized by phagocytes (primarily a direct uptake of crystals, similar to what is described for asbestos fibers). On the contrary,whole parasites appear to follow a classical endocytic pathway. This suggests that there may be differences between the ingestion of free particles and whole parasites in terms of modulation of phagocytes' functions.     

Spontaneous and pronase‐induced HER2 truncation increases the trastuzumab binding capacity of breast cancer tissues and cell lines

A subgroup of HER2‐overexpressing breast tumours co‐expresses p95 $^{{\rm{HER2}}}$ , a truncated HER2 receptor that retains a functional HER2 kinase domain but lacks the extracellular domain, thus impairing trastuzumab binding. We evaluated p95 $^{{\rm{HER2}}}$ expression in 99 frozen breast carcinoma samples by western blot analysis. The HER2‐positive cell line BT474 treated with pervanadate or pronase was used as a positive control for p95 $^{{\rm{HER2}}}$ expression. Immunohistochemistry was performed on parallel formalin‐fixed, paraffin‐embedded sections of the same case series using antibodies directed against either the intra‐ or extra‐cellular binding domain of HER2. In particular, biotinylated trastuzumab (BiotHER) was used to evaluate the binding capacity of the humanized antibody. To avoid a subjective evaluation of the score values and the percentage of immunostained cells, the slides were scanned and automatically analysed. The number of cases with HER2 overexpression (score 3+) and HER2 gene amplification was higher in the p185 $^{{\rm{HER2}}}$ ‐positive/p95 $^{{\rm{HER2}}}$ ‐positive samples than in the p185 $^{{\rm{HER2}}}$ ‐positive/p95 $^{{\rm{HER2}}}$ ‐negative group. Automated analysis confirmed a significantly higher percentage of 3+ scored cells in p95 $^{{\rm{HER2}}}$ ‐positive cases. Conversely, the percentage of 2+ scored cells was higher in p95 $^{{\rm{HER2}}}$ ‐negative cases. The status of the HER2 extracellular domain was then studied using flow cytometry on BT474 cells after pronase enzymatic digestion using trastuzumab and pertuzumab, while the presence of HER2‐HER3 dimers was studied using a proximity‐ligation assay. In vitro experiments showed that short‐term pronase digestion of BT474 cells produced two HER2 fragments (of 95 and 150 kDa, detectable in tissue specimens as well), increased the binding affinity of trastuzumab, reduced the rate of HER2–HER3 dimers, and did not interfere with pertuzumab‐binding capacity. In conclusion, the presence of p95 $^{{\rm{HER2}}}$ as detected by western blot analysis does not compromise the immunohistochemical detection of HER2. Our data suggest that a reduction of the receptor steric hindrance as induced by enzymatic shedding may facilitate the binding capacity of trastuzumab. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Effect of arm position on the prediction of kinematics from EMG in amputees

Myoelectric control has been extensively applied in multi-function hand/wrist prostheses. The performance of this type of control is however, influenced by several practical factors that still limit its clinical applicability. One of these factors is the change in arm posture during the daily use of prostheses. In this study, we investigate the effect of arm position on the performance of a simultaneous and proportional myoelectric control algorithm, both on trans-radial amputees and able-bodied subjects. The results showed that changing arm position adversely influences the performance of the algorithm for both subject groups, but that this influence is less pronounced in amputee subjects with respect to able-bodied subjects. Thus, the impact of arm posture on myoelectric control cannot be inferred from results on able-bodied subjects and should be directly investigated in amputee subjects.