Evaluation of the efficacy of topical sucralfate on healing haemorrhoidectomy incision wounds and reducing pain severity: A randomised clinical trial

The healing of haemorrhoidectomy wounds is a main concern of surgeons and patients. Various modalities can improve the quality of wound care after surgery. Antibiotics and topical agents, such as solutions and ointments, have been evaluated. The current research investigates the effects of sucralfate ointment on wound healing (epithelialisation) and postoperative pain after open haemorrhoidectomy. This trial involves two groups of randomly collected patients (n = 40) who underwent open haemorrhoidectomy surgery by the Milligan‐Morgan method. A 10% topical sucralfate ointment was applied to the investigated group''s wounds, while the control group patients used Vaseline as a placebo. The present work measured the two outcomes as follows: pain severity by a Visual Analogues Scale (VAS) score and epithelialisation by a surgeon''s visual inspection. During the postoperative phase, the mean VAS was 3.70 for the investigated group and 6.90 for the control group. On the average, the completion of epithelialisation for the investigated group was on day 13 as opposed to day 20 for the control group. The topical application of sucralfate ointment on post‐haemorrhoidectomy wound is an effective method for the promotion of healing, also lessens the severity of pain, and reduces the need for analgesics.     

Characterization of occult hepatitis B virus from blood donors carrying genotype A2 or genotype D strains

BACKGROUND/AIMS: Nucleic acid testing (NAT) for hepatitis B virus (HBV) DNA in blood donations identified occult HBV infection (OBI) as a potential threat to blood safety. METHODS: A collaborative study was undertaken to explore the molecular basis of OBIs prevalent in Europe in relation to clinical and serological data. RESULTS: Ninety-one percent of 77 donor samples of European origin HBV DNA positive but HBV surface antigen (HBsAg) negative were confirmed. Viral load ranged between unquantifiable and 5640IU/mL (median 25IU/mL). Fifty-two strains were genotyped (14 HBV(A2) and 38 HBV(D)). Compared to HBsAg+ samples, genotype D was significantly more frequent than genotype A2 in OBIs from Poland or Italy (P<0.04). Amino acid substitutions were concentrated in the immunologically active parts of the Pre-S/S proteins (P<0.0001) affecting both cellular CD8 T-cell epitopes and B-cell neutralizing Major Hydrophilic Region epitopes. Substitutions were more frequent in OBIs than in HBsAg+ strains of both genotype D (P<0.001) and A2 (P<0.01), in OBIs of genotype D than A2 in the 'a' region (P<0.001) but not cellular epitopes, and in anti-HBs+ than anti-HBs- OBIs (P<0.001). CONCLUSIONS: Results support the hypothesis that humoral and cellular immune pressure on the HBV envelope proteins are major mechanisms generating OBI.     

T cell receptor gene rearrangements define a monoclonal T cell proliferation in patients with T cell lymphocytosis and cytopenia

We have used probes from the T cell receptor beta and gamma chain loci to investigate the clonality of T lymphocytes in eight patients with T cell lymphocytosis and cytopenia (TCLC). This syndrome, which is strongly associated with rheumatoid arthritis, is characterized by peripheral blood and bone marrow lymphocytosis and neutropenia, red cell aplasia, or both. By means of T cell monoclonal antibodies and flow cytometry, T lymphocytes from patients with this syndrome have been shown to have characteristic immunologic features. Investigators have disagreed as to whether the syndrome represents a T cell malignancy or a more benign immunologic disorder. DNA from five of five patients with symptomatic "classic" T cell lymphocytosis with cytopenia demonstrated unique rearrangements of the T cell receptor beta chain locus, whereas neither of two patients with atypical features showed rearrangement. In addition, we found evidence for gamma chain rearrangement in those DNAs with clonal beta chain rearrangement. We thus postulate that the classic form of this syndrome is associated with a monoclonal proliferation of T cells. Its potential relationship to T cell chronic lymphocytic leukemia is discussed.     

Preclinical Activity of VX-787, a First-in-Class,Orally Bioavailable Inhibitor of the Influenza Virus Polymerase PB2 Subunit

VX-787 is a novel inhibitor of influenza virus replication that blocks the PB2 cap-snatching activity of the influenza viral polymerase complex. Viral genetics and X-ray crystallography studies provide support for the idea that VX-787 occupies the 7-methyl GTP (m⁷GTP) cap-binding site of PB2. VX-787 binds the cap-binding domain of the PB2 subunit with a K_D (dissociation constant) of 24 nM as determined by isothermal titration calorimetry (ITC). The cell-based EC₅₀ (the concentration of compound that ensures 50% cell viability of an uninfected control) for VX-787 is 1.6 nM in a cytopathic effect (CPE) assay, with a similar EC₅₀ in a viral RNA replication assay. VX-787 is active against a diverse panel of influenza A virus strains, including H1N1pdm09 and H5N1 strains, as well as strains with reduced susceptibility to neuraminidase inhibitors (NAIs). VX-787 was highly efficacious in both prophylaxis and treatment models of mouse influenza and was superior to the neuraminidase inhibitor, oseltamivir, including in delayed-start-to-treat experiments, with 100% survival at up to 96 h postinfection and partial survival in groups where the initiation of therapy was delayed up to 120 h postinfection. At different doses, VX-787 showed a 1-log to >5-log reduction in viral load (relative to vehicle controls) in mouse lungs. Overall, these favorable findings validate the PB2 subunit of the viral polymerase as a drug target for influenza therapy and support the continued development of VX-787 as a novel antiviral agent for the treatment of influenza infection.     

Cisatracurium in cardiac surgery--continuous infusion vs. bolus administration

The aim of this study was the comparison of infusion vs. intermittent bolus administration of cisatracurium (CA) following cardiac surgery with regard to total intraoperative dose and time of recovery from neuromuscular blockade. From June 2005 to April 2006 sixty ASA II-III patients who were undergoing coronary bypass graft and valve replacement surgery, were equally divided and randomized to receive either intermittent bolus (Group A, n = 30) or continuous infusion (Group B, n = 30) of CA in Madani Heart Center in the Tabriz (Iran). Total intraoperative dose of CA and time to TOF ratio = 0.8 after operation were measured. Anesthesia technique in two groups was the same. All of the patients underwent cardiopulmonary bypass. Intensity of neuromuscular blockade maintained on one train-of-four (TOF) twitch response of adductor pollicis during operation. Mean received dose of CA was 32.8 +/- 20.6 micro/kg/hr in Group A and 89.7 +/- 39.4 micro/kg/hr in Group B (p = 0.003). Total intraoperative dose of CA was 23.6 +/- 4.9 mg in Group A and 39.2 +/- 10.1 mg in Group B (p = 0.001). Spontaneous recovery from neuromuscular blockade in ICU (TOF ratio = 0.8) was reached in 43.8 +/- 9.2 min in Group A, and 64.2 +/- 15.1 min in Group B (p = 0.0001). Intubation time in ICU was not significantly different (Group A = 8.3 +/- 5.1 hrs vs. Group B = 10.2 +/- 6.2 hrs, p = 0.256). These results support the intermittent bolus administration of cisatracurium in cardiac surgery following cardiopulmonary bypass.     

The antitumor efficiency of combined electrochemotherapy and single dose irradiation on a breast cancer tumor model

Background

The aim of this study was to investigate the antitumor effectiveness of electrochemotherapy with cisplatin combined with suboptimal radiotherapy doses. Tumor radiosensitization was evaluated on large invasive ductal carcinoma tumors in Balb/C mice.

Materials and methods

Tumors of an average volume of 630 mm³ were treated with cisplatin, electric pulses, radiotherapy, electrochemotherapy, alone as well as in appropriate combinations. Tumors were irradiated with Cobalt-60 γ-rays at doses 3 Gy and 5 Gy in combination with electrochemotherapy using cisplatin. Controls included each of the treatments alone as well as the combination of the radiotherapy with electric pulses alone or with cisplatin alone. Antitumor effectiveness was evaluated by tumor growth delay, tumor-doubling time, inhibition ratio and the objective response rates.

Results

As anticipated, electrochemotherapy was more effective than the treatment with cisplatin alone or the application of the electric pulses alone. When treatments were combined with tumor irradiation at either 3 or 5 Gy, the combination with electrochemotherapy was more effective: at 5 Gy, 2 animals out of 8 were in complete remission 100 days later. In general the higher 5 Gy dose of γ-radiation was more effective than the lower one of 3 Gy.

Conclusions

The results of our study demonstrate that irradiation doses, 3 Gy or 5 Gy, increase the antitumor effectiveness of electrochemotherapy with cisplatin on invasive ductal carcinoma tumors. Good antitumor results were achieved in experimental tumors with a size comparable to clinical lesions, demonstrating that this three-modality combined treatment is useful for the treatment of large lesions even at sub-optimal radiotherapy doses.     

Diagnostic values of GHSR DNA methylation pattern in breast cancer

DNA methylation patterns have been recognised as cancer-specific markers with high potential for clinical applications. We aimed at identifying methylation variations that differentiate between breast cancers and other breast tissue entities to establish a signature for diagnosis. Candidate genomic loci were analysed in 117 fresh-frozen breast specimens, which included cancer, benign and normal breast tissues from patients as well as material from healthy individuals. A cancer-specific DNA methylation signature was identified by microarray analysis in a test set of samples (n?=?52, p?0.99). To date, this represents the DNA methylation marker of the highest sensitivity and specificity for breast cancer diagnosis. Functionally, ectopic expression of GHSR in a cell line model reduced breast cancer cell invasion without affecting cell viability upon stimulation of cells with ghrelin. Our data suggest a link between epigenetic down-regulation of GHSR and breast cancer cell invasion.     

Automatic threshold selection algorithm to distinguish a tissue chromophore from the background in photoacoustic imaging

The adaptive matched filter (AMF) is a method widely used in spectral unmixing to classify different tissue chromophores in photoacoustic images. However, a threshold needs to be applied to the AMF detection image to distinguish the desired tissue chromophores from the background. In this study, we propose an automatic threshold selection (ATS) algorithm capable of differentiating a target from the background, based on the features of the AMF detection image. The mean difference between the estimated thickness, using the ATS algorithm, and the known values was 0.17 SD (0.24) mm for the phantom inclusions and -0.05 SD (0.21) mm for the tissue samples of malignant melanoma. The evaluation shows that the thickness and the width of the phantom inclusions and the tumors can be estimated using AMF in an automatic way after applying the ATS algorithm.