Real life results of direct acting antiviral therapy for HCV infection in HIV-HCV-coinfected patients: Epi-Ter2 study.

The aim of this study was to evaluate the baseline demographics and real-life efficacy of direct acting antivirals (DAAs) in HIV-HCV-positive patients as compared to patients with HCV monoinfection. The analysis included 5690 subjects who were treated with DAAs: 5533 were HCV-positive and 157 were HIV-HCV-positive. Patients with HCV-monoinfection were older (p < .0001) and in HIV-HCV group there were more men (p < .0001). Prevalence of genotype 1a (p = .002), as well as of genotypes 3 and 4 (p < .0001) was higher in HIV-HCV-coinfected patients. Genotype 1b was more frequent (p < .0001) in the HCV-mono-infection group. Patients with HCV-monoinfection had a higher proportion of fibrosis F4 (p = .0004) and lower proportion of fibrosis F2 (p < .0001). HIV-HCV-coinfected individuals were more often treatment-naïve (p < .0001). Rates of sustained viral response after 12 weeks did not differ significantly between both groups (95.9% versus 97.3% in coinfection and monoinfection group, respectively; p > .05). They were, however, influenced by HCV genotype (p < .0001), stage of hepatic fibrosis (p < .0001), male sex (p < .0001), BMI (p = .0001) and treatment regimen modifications (p < .0001). Although factors associated with worse response to therapy (male sex, genotype 3) occurred more often in the HIV coinfection group, real-life results of DAAs did not differ significantly between both populations.

Investigation of phonons and magnons in [Ni80Fe20/Au/Co/Au]Nmultilayers.

The interaction between phonons and magnons is a rapidly developing area of research, particularly in the field of acoustic spintronics. To discuss this interaction, it is necessary to observe two different waves (acoustic and spin waves) with the same frequency and wavelength. In the Ni80Fe20/Au/Co/Au system deposited on a silicon substrate, we observe the interaction between spin waves and surface acoustic waves using Brillouin light scattering spectroscopy. As a result, we can selectively control (activate or deactivate) the magnetoelastic interaction between the fundamental spin wave mode and surface acoustic waves. This is achieved by adjusting the magnetostrictive layer thickness in the multilayer. We demonstrate that by adjusting the number of layers in a multilayer structure, it is possible to precisely control the dispersion of surface acoustic waves while having minimal impact on the fundamental spin wave mode.

Prevalence of Chlamydia trachomatis and herpes simplex virus 2 in cervical carcinoma associated with human papillomavirus detected in paraffin-sectioned samples.

PURPOSE: The aim of the study was to evaluate the frequency of occurrence of HPV and co-infection: Chlamydia (C.) trachomatis and HSV-2 in cervical cancer. MATERIAL AND METHODS: The study group consisted of 570 paraffin-sectioned samples of patients with cervical cancer. In order to identify viral and bacterial DNA in DNA isolated from archival, postoperative material, PCR analysis was performed using starters complementary to various types of HPV, HSV-2 and C. trachomatis. RESULTS: In patients with squamous cell cervical cancer the presence of 33 types of HPV was found in 90% (468/520). HPV 16 infections occurred in 69.4% (325/468), while HPV 18 infections were present in 30.5% (143/468) of cases. In the control group C. trachomatis and HSV-2 were observed in four cases (4/50), which constitute 8.0%. In the tissue sections from patients with squamous cell cervical carcinoma, C. trachomatis was identified in 26% (135/520) and HSV-2 in 28% (145/520). In the group of patients with adenocarcinoma C. trachomatis infections were found in 24% (12/50) and herpes virus was identified in 30% (15/50). Statistically significantly higher frequency of occurrence of HSV-2 and C. trachomatis was observed in paraffin-sectioned samples for patients with invasive cervical cancer compared to the control group, without neoplastic lesions (p < 0.05). No correlation was found between frequency of occurrence of HPV and C. trachomatis and of HPV and HSV-2 detected in paraffin-sectioned samples for cervical carcinoma.

Hepatitis C virus core antigen as a possible alternative for evaluation of treatment effectiveness after treatment with direct-acting antivirals.

Background: Chronic hepatitis C is a major public health problem around the world. In monitoring treatment efficacy, although costly and labour-intensive methods of molecular biology are often used, much cheaper and technically easier serological methods evaluating the concentration of HCV core antigen in serum are available. We evaluated HCVcAg quantification as a possible assessment of the treatment efficacy instead of HCV RNA quantification.Methods: We collected 514 serum samples from treated HCV infected patients. Quantitative evaluation of HCV RNA and HCVcAg was carried out before treatment, at the end of treatment, and at least 12 weeks following treatment termination. HCV RNA was determined by automated assay (Roche COBAS) and HCVcAg quantitation with ARCHITECT ci8200 analyser.Results: There was a significant correlation between HCVcAg and HCV RNA concentrations at baseline and follow-up visits, but not at the end of treatment. Among samples collected before the treatment, at the end of treatment and follow-up visit, concordance of HCV RNA and HCVcAg reached level of 98.1%, 98.9% and 98.7%, respectively. Diagnostic sensitivity, specificity, positive and negative predictive values of HCVcAg detection were >97%.Conclusions: HCVcAg measurement could be an alternative for determining HCV treatment efficacy after chemotherapy and could be an option in the diagnosis of HCV infection.

Chlamydia trachomatis and herpes simplex virus 2 infection in vulvar intraepithelial neoplasia associated with human papillomavirus.

BACKGROUND: The role of viral and bacterial co-infection is stressed in VIN. A view that VIN is a sexually transmitted disease made the area of research larger and stimulated scientists to seek other sexually transmitted factors, among which Chlamydia trachomatis and Herpes simplex are frequently examined. PURPOSE: The aim of the study was to evaluate the frequency of occurrence of HPV DNA and the frequency of co-infection with Herpes virus type 2 and Chlamydia trachomatis in VIN. MATERIAL AND METHODS: We identified archival diagnostic phase tissue specimens from 41 cases of vulvar intraepithelial neoplasia III. From the same paraffin blocks containing material from the margins of surgical sections during vulvectomy, normal epithelial tissue fragments were collected. They constituted the control group. Lesion characteristics were examined in comparison with the presence of HPV DNA, HSV-2 and Chlamydia trachomatsis. Identification was performed using PCR. RESULTS: In the study group HPV infection was found in 75.6% of cases. In 73% of cases it was HPV 16. In the control group we found HPV 16 DNA in only one case (2.43%). In the HPV positive study group HPV 16 was found in 30 (30/31) cases. In only one case (1/31) it was HPV 18 type. In the study group of 41 cases with VIN, HSV-2 infection was found in six cases (14.63%). In comparison with the control group (9.75%) the difference was not statistically significant. The frequency of occurrence of Chlamydia trachomatis in the analyzed study material was 14.63% (6/41) and in the control group it was 9.75% (4/41). The difference was not statistically significant. Statistical analyses of correlations between the occurrence of DNA HPV and HSV-2 as well as of HPV and Chlamydia trachomatis showed no correlation in either case. CONCLUSION: No correlation was found between the frequency of occurrence of HPV and HSV-2 and HPV and Chlamydia trachomatis in either group.

Purine metabolism in pigs and humans and its implications for xenotransplantation.

We compared concentrations of nucleotide substrates and activities of enzymes of nucleotide metabolism in pig and human blood, heart, and kidney. The most important difference was lower ecto-5-nucleotidase (ESN) activity in both pig hearts and kidney. Furthermore, higher hypoxanthine, inosine, adenine, and uracil, but lower uridine and uric acid concentrations were observed in pig blood as compared to human. A twofold increase in UTP concentration has been observed in pig hearts following 4 h perfusion with human blood. Purine metabolism is an important target for genetic and pharmacological manipulation during xenotransplantations.

Plasma exchange for the removal of digoxin-specific antibody fragments in renal failure: timing is important for maximizing clearance.

Life-threatening digoxin toxicity may be effectively treated with digoxin-specific antibody fragments (Fab). However, in end-stage renal disease, the digoxin-Fab complexes persist in the circulation and dissociate, potentially resulting in rebounding free digoxin levels and the recurrence of symptomatic toxicity. To prevent this rebound phenomenon, plasma exchange (PE) has been implemented for the removal of the digoxin-Fab complexes in renal failure. However, there is only one case report describing its use in this setting. To better determine the optimal timing of PE after Fab administration, we performed two PE treatments (each preceded by Fab) in a patient with acute renal failure and acute digoxin poisoning. The admission serum digoxin level was 21 ng/mL. The timing of the PE treatments relative to Fab dosing was as follows: the first PE was performed 26 hours post-Fab, and the second PE was performed 2.5 hours post-Fab. The plasma ultrafiltrate digoxin concentration was 2.5-fold greater when PE was performed 2.5 hours versus 26 hours after Fab administration (19.9 versus 8.1 ng/mL). The combined total amount of digoxin removed in the ultrafiltrate plasma was minimal (0.13 mg), less than 1% of the total amount of ingested drug. We conclude that the optimal timing of PE is within the first 3 hours after Fab administration. Although PE is efficacious for removing digoxin-Fab complexes, thus preventing rebound digoxin toxicity, it is not efficacious for improving total digoxin clearance because of the large apparent volume of distribution of digoxin (5 to 8 L/kg).

Principles of induction chemotherapy for non-small cell lung cancer.

The results of lung cancer treatment have not significantly improved for many years. About 35% of patients with non-small cell lung cancer (NSCLC) are in clinical stage IIIA. Clinically asymptomatic distant metastases occur in the majority of these patients. In such cases only combined treatment offers a chance of cure. In the Chest Surgery Center in Lublin a clinical trial was carried out aimed to assess late results of combined treatment in patients with IIIA NSCLC. Over 700 patients were enrolled in the study. The results of the trial disclosed, that neoadjuvant chemotherapy prolonged life of the operated patients and improved their life quality. However, a question of qualification for this complex treatment and complexity of assessment criteria, still remain to be answered.

Thermodynamical model of mixed aggregation of ligands with caffeine in aqueous solution. Part II.

A statistical-thermodynamical model of mixed association in which one component's self-association is unlimited while the second component does not self-aggregate is described. The model was tested with 4',6-diamidino-2-phenyl-indole-dihydrochloride (DAPI) and ethidium bromide (EB) using light absorption spectroscopy and calorimetry. The system is controlled by two parameters, which represent self-aggregation 'neighborhood' association constant KCC and mixed 'neighborhood' association constant KAC. Calculated, using this model, KAC = 58.2 +/- 1 M-1, KAC = 64.6 +/- 2 M-1 for DAPI and EB, respectively, are in good agreement with known values of stacking interactions. The titration microcalorimetric measurement of DAPI-CAF interaction delta H = -11.1 +/- 0.4 kcal/mol is also consistent with this type of reaction. The structures of the stacking complexes were also confirmed by semi-empirical molecular modeling in the presence of water. The data indicate that CAF forms stacking complexes with DAPI and EB, thus effectively lowering the concentration of the free ligands in the solution, and therefore, CAF can be used to modulate aromatic compound activity.

Expression of p21 and bcl-2 proteins and p53 mRNA in surgically resected preparations of non-small cell lung cancer (stage IIIA) after etoposide and cisplatin chemotherapy.

Apoptosis which is also a called programmed cell death plays an important role during development, homeostasis and in many diseases such as cancer. Apoptosis is a genetically encoded cell death program defined by characteristic morphological and biochemical features. It is well recognized as a distinct pathologic mechanism in tumours responding to anticancer therapies. Many genes play an important role in this process. We evaluated an expression of the tumour supressor gene p53 and proteins p21 and bcl-2 in non-small cell lung cancer. We examined resected tumour tissues from 30 patients who received neoadjuvant chemotherapy. As a control we assessed tissues from patients treated without chemotherapy. Histological slides of the resected tumours were evaluated by TUNEL, in situ hybridisation and with immunoperoxidase staining procedure. The results were documented by photography. We examined the level of extinction using cytophotometry. In conclusion, preoperative chemotherapy induces apoptosis in cancer cells. The level of p53 correlates with the acceleration of TUNEL reaction. The loss of bcl-2 expression correlated with an increased apoptotic cell death. There was an increased p21 protein expression in the examined cancer tissues after chemotherapy.

Immunohistochemical study of p53 in non-small cell lung cancer before and after preoperative chemotherapy.

The purpose of the study was to assess the expression of p53 in non-small cell lung cancer (NSCLC) before and after treatment with cisplatin and vepeside (PE) and to define a relationship between p53 expression and responsiveness to chemotherapy prior to surgery. Material for study consisted of specimens obtained from neoplastic infiltrate before chemotherapy (biopsy material) and tumour specimens obtained after chemotherapy (surgical material). The study population was a group of 35 patients with stage IIIA NSCLC. p53 protein accumulation was detected by immunohistochemistry using antibodies against p53: NCL-p53 (clone BP-53-12) (Novocastra) on paraffin embedded specimens. p53 expression was found in 21 patients (60%) before and after chemotherapy. In 14 patients (40%) p53 negativity was seen both in biopsy and surgical material. The level of p53 staining after chemotherapy as compared with that before treatment changed from -53 to +34. There was a mean increase by 1.52, which appeared statistically accidental (p > 0.70). There was no significant relationship between p53 expression and responsiveness to chemotherapy (from p > 0.33 to p > 0.70) and between the magnitude of changes in p53 expression and response to chemotherapy (p > 0.39). There was also a very low correlation (r to 0.10; p > 0.50) between responsiveness to therapy and p53 negativity.

Expression of PCNA in non-small cell lung cancer before and after treatment with cisplatin and vepeside.

The purpose of the study was to assess expression of the proliferating cell nuclear antigen (PCNA) in non-small cell lung cancer (NSCLC) after administration of cisplatin and vepeside in patients with clinical stage IIIA and to define a relationship between PCNA expression and tumour responsiveness to preoperative chemotherapy. An immunohistochemical study with a mouse monoclonal antibody against PCNA (Novocastra, Clone PC10, IgG2a Class) was performed on paraffin embedded specimens using the ABComplex/HRP method. Material for study was available from 35 patients and consisted of biopsy specimens obtained from neoplastic infiltrate before chemotherapy and tumour specimens obtained from the same patients during surgery 3-4 weeks after chemotherapy. PCNA immunoreactivity was observed in all the cases (100%) both before and after chemotherapy. Despite treatment with cisplatin and vepeside prior to surgery the PCNA index (IPCNA) was significantly higher (p < 0.002) irrespective of tumour responsiveness to chemotherapy. There was a positive correlation (p < 0.04) between tumour size and IPCNA after chemotherapy in a group of patients with a similar extent of neoplastic infiltrate. No correlation was seen between PCNA expression in biopsy specimens and tumour responsiveness to chemotherapy.

Protein kinase CK2 mediates TGF-beta1-stimulated type IV collagen gene transcription and its reversal by estradiol.

BACKGROUND: We have previously shown that the transcription factor Sp1 mediates the stimulatory effects of transforming growth factor-beta1 (TGF-beta1) on type IV collagen gene transcription and protein synthesis, and that estradiol reverses these effects by down-regulating Sp1 activity. Protein kinase casein kinase II (CK2) phosphorylates Egr-1 and prevents its binding to Sp1. We hypothesized that TGF-beta1 stimulates CK2 activity, which in turn activates type IV collagen gene transcription via increased availability of free Sp1. METHODS: The effects of TGF-beta1 and of estradiol on murine mesangial cell type IV collagen gene transcription were measured using a reporter mini gene construct and on collagen IV protein synthesis by Western blotting. Nuclear Egr-1, phosphorylated Egr-1, Sp1, Egr-1/Sp1 complexes and unbound Sp1 were measured using co-immunoprecipitation and Western blotting techniques. RESULTS: TGF-beta1 stimulated CK2 activity in murine mesangial cells. Although TGF-beta1 failed to alter total Egr-1 protein, it increased phosphorylated Egr-1. This led to decreased Egr-1/Sp1 complex formation, increased unbound Sp1, increased binding of nuclear extracts to the collagen IV promoter, and increased type IV collagen gene transcription and protein synthesis. Physiologic concentrations of estradiol reversed these effects. CONCLUSIONS: These studies suggest that activation of CK2 mediates the stimulatory effect of TGF-beta1 on type IV collagen gene transcription. Moreover, the ability of estradiol to reverse TGF-beta1-stimulated type IV collagen synthesis is mediated by down-regulating CK2 activity, which ultimately limits the availability of unbound Sp1 to activate gene transcription.

A randomized trial of minidose warfarin for the prevention of late malfunction in tunneled, cuffed hemodialysis catheters.

BACKGROUND: Minidose warfarin (1 mg/day) has been associated with a 74% reduction in the thrombosis rate of central venous catheters used in oncology patients. To determine the efficacy of minidose warfarin on late malfunction caused by thrombosis or fibrin sheath formation in tunneled, cuffed catheters (TCC) used for hemodialysis (HD), we performed a randomized, placebo-controlled trial. METHODS: One hundred five chronic HD patients with TCCs were initially randomized. Of these, 85 (warfarin 41 and placebo 44) completed the first two weeks of the protocol and were followed for the first year of TCC life or until TCC removal. RESULTS: Sixteen TCCs failed with late TCC malfunction, eight in each group. In a multivariate analysis, there was no significant effect of warfarin on thrombosis-free TCC survival or time to the first urokinase (UK) instillation for incipient thrombosis. The presence of a low hemoglobin (Hgb; <10.5 g/dL) or a low international normalized ratio (INR; <1.00) was significantly associated with a higher risk of late TCC malfunction (RR 5.2 and 4.0, respectively), a higher risk of incipient TCC thrombosis requiring UK (RR 2.0 and 2.8, respectively), and higher rates of UK dosing. Diabetics had a 3.6-fold higher risk of late TCC malfunction and a twofold higher risk of incipient thrombosis requiring UK, although these findings were not statistically significant. Aspirin use, race, age, number of hospitalizations, erythropoietin dose, intradialytic heparin dose, serum albumin, and the number of episodes of TCC-associated infection were not significantly associated with late TCC malfunction. CONCLUSIONS: Thrombosis prophylaxis using fixed minidose warfarin is not efficacious in TCCs used for HD. However, the present data suggest improved TCC survival in patients with an INR> 1.00. Patients with diabetes and those with a low Hgb or INR have a higher risk of late TCC malfunction.

[Epidemiologic and clinical tests of patients suffering from laryngeal cancer in the Lublin macro-region in the years 1991-1995]. / Badania epidemiologiczne i kliniczne chorujacych na raka krtani w latach 1991-1995 w makroregionie lubelskim.

The study of registered morbidity of patients suffering from laryngeal cancer in the Lublin macro-region in the years 1991-95 was carried out. Morbidity rates in the population in consecutive years of investigated 5-year age groups were examined. In clinical investigations the conditions of clinical advancement of the disease in particular organs was determined and environmental factors and occupation were also revealed.