Inhibition of the binding of HCV serum particles to human hepatocytes by E1E2‐specific D32.10 monoclonal antibody

The aim of this study was to determine the inhibition of binding activity of the monoclonal antibody (mAb) D32.10 which recognizes a highly conserved discontinuous antigenic determinant (E1:297–306, E2:480–494, and E2:613–621) expressed on the surface of serum‐derived HCV particles (HCVsp) of genotypes 1a, 1b, 2a, and 3a. To this end, an in vitro direct cell‐binding assay based on the attachment of radiolabeled HCVsp was developed, and Scatchard plots were used to analyze ligand–receptor binding data. HCV adsorption was also assessed by quantitating cell‐associated viral RNA by a real‐time RT‐PCR method. Saturable concentration‐dependent specific binding of HCVsp to Huh‐7 or HepaRG cells was demonstrated. The Scatchard transformed data showed two‐site interaction for Huh‐7 and proliferative HepaRG cells: the high‐affinity binding sites (K_d1 = 0.1–0.5 µg/ml) and the low‐affinity binding sites (K_d1 = 5–10 µg/ml), and one‐site high‐affinity binding model between E1E2/D32.10‐positive HCVsp and hepatocyte‐like differentiated HepaRG cells. The E1E2‐specific mAb D32.10 inhibited efficiently (>60%) and selectively the binding with an IC₅₀ ≤0.5 µg/ml in all the experimental approaches using serum HCV of genotype either 3 or 1b. This supports the involvement of the E1E2/D32.10 discontinuous antigenic determinant in the interactions between human hepatocytes and HCVsp, and suggests that D32.10‐like antibodies present in sera from patients infected with HCV could play a protective role. J. Med. Virol. 81:1726–1733, 2009. © 2009 Wiley‐Liss, Inc.     

Oestrogen and cortisol producing adrenal tumour.

A 14 year old boy is presented who was admitted to the psychiatric ward because of delirium. He also had gynaecomastia, facial oedema, striae, and hypertension. He was finally proved to have a mixed oestrogen and cortisol producing adrenal tumour which was removed surgically with complete improvement and no relapse.     

Transrectal ultrasound in the diagnosis of prostate cancer

Transrectal ultrasound is an important tool in detection and management of prostate cancer. Its role is to identify and characterize focal lesions before capsular invasion and metastases and to guide biopsy of the prostate. In this paper, we present a overview of the state of trans-rectal ultrasound imaging in prostate cancer.     

Risk of bleeding and restenosis among chronic kidney disease patients undergoing percutaneous coronary intervention

BACKGROUND: Bleeding risk is increased in renal failure due to impaired platelet adhesiveness. Patients who undergo percutaneous coronary intervention (PCI) are given multiple antiplatelet agents that increase that risk. We retrospectively tested the hypothesis that chronic kidney disease (CKD) patients who undergo PCI are at higher risk of bleeding and restenosis (due to chronic inflammation) compared to patients with normal renal function. METHODS: Patients who had PCI for non-ST elevation myocardial infarction or unstable angina between July 2001 and June 2003 (1,184 patients) were included in the study. All the patients were given periprocedural clopidogrel, aspirin and glycoprotein IIb/IIIa inhibitor if indicated, and then continued on clopidogrel and aspirin daily for 12 months. The patients were classified into 5 groups according to the CKD stage and followed-up for 12 months for development of major or minor bleeding, restenosis, length of hospital stay and survival. RESULTS: The incidence of major bleeding within the first month (3.4% in normal kidney function patients (Gp 1), 4.8% for CKD Stages 1 and 2 patients (Gp2), 5.2% for CKD Stage 3 patients (Gp3), 6.1% for CKD Stage 4 patients (Gp4) and 9.3% for CKD Stage 5 patients (Gp5), p = 0.001) and for minor bleeding (5.7% in Gp1, 6.5% for Gp2, 7.4% for Gp3, 9.2% for Gp4 and 11.3% for Gp5, p = 0.001) and the incidence of restenosis at one month (4.6% in Gp1, 5.3% for Gp2, 6.8% for Gp3, 7.3% for Gp4 and 9.6% for Gp5, p = 0.001) and 6 months (11.2% in Gp1, 13.5% for Gp2, 15.7% for Gp3, 16.4% for Gp4 and 19.7% for Gp5, p = 0.001) were higher with worsening CKD. Survival at one year was worse with worsening of the kidney function. CONCLUSION: Worsening of CKD is associated with progressively increased risk of minor and major bleeding, restenosis and death during and after PCI.     

A nonrandomized comparison of the clinical outcome of ocular involvement in patients with mucous membrane (cicatricial) pemphigoid between conventional immunosuppressive and intravenous immunoglobulin therapies

The purpose of this study was to compare the clinical outcomes of intravenous immunoglobulin (IVIg) therapy to conventional immunosuppressive therapy in patients with mucous membrane pemphigoid (MMP), also known as cicatricial pemphigoid (CP), whose disease progressed to involve the eye. Before ocular involvement, all the patients in this study were diagnosed and treated with immunosuppressive agents, for biopsy-proven MMP, affecting the skin and/or mucous membranes, other than the conjunctiva. Eight patients in group A were treated with IVIg after the diagnosis of ocular cicatricial pemphigoid (OCP) was established. The efficacy and safety of IVIg therapy were compared to a clinically similar group of eight patients treated with conventional immunosuppressive therapy (group B). The inclusion criteria for both groups were: (1). presence of MMP at extraocular sites confirmed by biopsy before entry into the study; (2). entry into the study occurred when ocular involvement was noted and confirmed by biopsy; (3). presence of conventional immunosuppressive therapy at the time of ocular involvement; (4). a minimum of 18 months of follow-up after diagnosis of ocular involvement. The mean length of the therapy, after the onset of ocular involvement, was 24 months (range 16-30) in group A and 45 months (range 21-90) in group B. The median time between initiation of therapy and clinical remission in group A and group B was 4 and 8.5 months, respectively. This difference was statistically significant (P < 0.01). No recurrence of ocular inflammation was recorded in any of the patients in group A. On the contrary, at least one recurrence (median 1) was recorded in five patients in group B (range 0-4). This difference was statistically significant (P < 0.05). All eight patients in group A and group B presented to the ophthalmologist in stage 2 of OCP at the time of the initial visit. At the last follow-up visit, no progression to advanced stages of OCP was recorded in all eight patients in group A. On the contrary, only four patients in group B remained in stage 2 of OCP at the last follow-up exam. The conjunctival scaring progressed from stage 2 to stage 3 in the remaining four patients of group B. At the last follow-up visit, both eyes of each patient in group A were free of inflammation. Some level of conjunctival inflammation at the last follow-up visit was noted in five patients in group B (range 0-1.5, P < 0.05). Both groups of patients were studied during the same time period. The results of this study suggest that ocular involvement in patients with MMP may be considered an indication for initiating IVIg therapy, since it was more effective in arresting progression of OCP, when compared to conventional immunosuppressive therapy. These data indicate that IVIg produced a faster control of the acute inflammation and that no recurrences were observed during the follow-up. This clinical difference could be because of the reduced production of pathogenic antibody, and/or restoration of the immunoregulation, which may have been disturbed.     

Intravenous immunoglobulin therapy in patients with ocular-cicatricial pemphigoid: a long-term follow-up

OBJECTIVE: To report the clinical outcome and long-term follow-up of 10 patients with progressive ocular-cicatricial pemphigoid (OCP), nonresponsive to conventional therapy and treated with IV immunoglobulin (IVIg) therapy, reported earlier as a preliminary study. DESIGN: Noncomparative, prospective, interventional case series according to a defined protocol for IVIg therapy. PARTICIPANTS: Ten patients, with a diagnosis of OCP present bilaterally confirmed by both biopsy and immunofluorescence studies and who had failed conventional therapy and had objectively demonstrated a positive response to IVIg therapy in a preliminary study, published in 1999. MAIN OUTCOME MEASURES: Comparison of objective clinical outcome parameters before and after IVIg therapy, including visual acuity (VA) and prevention of progression of subepithelial conjunctival fibrosis and blindness. RESULTS: All 10 patients initially demonstrated signs of clinical improvement with IVIg therapy. The total number of IVIg cycles ranged from 20 to 42 (mean, 32), and the total duration of IVIg therapy ranged from 25 to 43 months (mean, 35). Eight patients who completed the protocol had an improvement in their VA and did not have further progression of subepithelial conjunctival fibrosis. These 8 patients have been maintained in a sustained remission for a total follow-up period ranging from 24 to 48 months (mean, 35) after the discontinuation of IVIg therapy. Two patients did not complete the protocol. Both had initially demonstrated a positive clinical response. One patient had worsening of the OCP and, after IVIg therapy, was abruptly and involuntarily withdrawn. In the second patient, deterioration occurred after ocular surgery. Intravenous immunoglobulin therapy was not provided postoperatively. These 2 patients who did not complete the protocol lost vision. CONCLUSIONS: Intravenous immunoglobulin therapy is an effective treatment in OCP in patients nonresponsive to conventional therapy. In 8 patients who completed the protocol, progression of the disease was not observed. A gradual withdrawal of IVIg therapy, as described in the protocol, may be beneficial in maintaining a sustained clinical remission. Abrupt cessation or discontinuation can result in a severe recurrence that may possibly progress to blindness.     

Successful thrombolysis on an aortic valve prosthesis by plasminogen tissue activator during pregnancy]

The authors report the case of a 28 year old woman admitted as an emergency at 15 weeks' amenorrhea for malaise with transient aphasia and orthopnoea due to massive thrombosis of a St Jude aortic valve prosthesis implanted two years previously. This complication occurred after relay of oral anticoagulants with subcutaneous heparin therapy. After a medico-surgical and obstetrical discussion, the indication for thrombolytic therapy with 50 mg of rt-PA over two hours was decided with an excellent clinical and echocardiographic, immediate and lasting result, without any maternal or foetal complication. This enabled pregnancy to be continued to term under oral anti-coagulant therapy. Caesarean section was performed at 8 months leading to the birth of a healthy child. Echocardiographic and radioscopic parameters in the post-partum period showed good prosthetic valve function with no indication for reoperation. This case is original by the absence of neurological and obstetrical complications of thrombolysis, the continuation of pregnancy to term and complete lysis of the thrombus without replacement of the valvular prosthesis.