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Biomedical subjects

Andrzej Gładysz

Publications and source records attributed to Andrzej Gładysz.

At least 19 recordsLinked to original sources

Lung cancer as an immune reconstitution disease in an HIV-1 positive man receiving HAART.

A case of small-cell lung cancer with prompt worsening of the clinical course was observed in a patient with significant immune restoration after receiving effective highly active antiretroviral therapy (HAART) for seven months. Rapid and enormous enlargement of metastatic liver was the main symptom. Chest x-ray showed an enlargement of the left hilus. The patient died 22 days after the onset of the fulminant disease. We suggest that the occurrence and aggressive course of the lung cancer resulted from the development of immune reconstitution syndrome.

Adult↗

Non-Hodgkin's lymphoma as a rare manifestation of immune reconstitution disease in HIV-1 positive patients.

Combination antiretroviral therapy (cART) can improve immune system function through suppression of HIV-1 replication. However, paradoxical immune response may develop in some patients as a result of effective therapy followed by immune restoration. The phenomena is known as IRS, immune reconstitution syndrome/immune recovery syndrome. IRS can develop within weeks to months after cART is commenced and the time is related to the type of the disease. There are but scant reports concerning IRS-NHL (non-Hodgkin's lymphoma) in HIV-1 positive subjects. We observed 4 (33%) cases of IRS-NHL out of 12 patients in whom NHL was diagnosed. As a result of potent cART they reached viral suppression in a mean time of 15 weeks followed by a rise in CD4(+) T cells within 16.5 weeks. The diagnosis of NHL was established at a mean time of 36 weeks after cART was introduced and 20 weeks after the CD4 T cell increase was achieved. This may indicate that the immune reconstitution as a result of cART was a predisposing factor for the development of NHL in our patients. There was prompt progression of the disease and the outcome was fatal in all cases. IRS-NHL should be suspected in any case of lymphadenopathy, generalized or limited to the abdomen or periphery, which develops after immune recovery due to potent cART within a few months.

Adult↗

[Immune reconstitution syndromes secondary to effective antiretroviral therapy].

Highly active antiretroviral therapy (HAART) can improve immune system function through suppression of HIV-1 replication. In some cases, a vigorous paradoxical immune response may develop. Individuals treated effectively can, because of low immune reactivity, suffer from diseases which run subclinically until HAART is introduced. These symptoms are termed IRS (immune reconstitution syndrome/immune recovery syndrome), IRD (immune restoration disease), and IRIS (immune restoration inflammatory syndrome). There are some predisposing factors, such as long-lasting HIV-1 infection, severe immunodeficiency, rapid immune restoration, immune dysregulation during immune reconstitution, subclinical infection, and genetic susceptibility. A common feature of IRS is clinical symptoms different from those observed usually in HIV-1-infected patients. Sarcoidosis and some autoimmune diseases are less common. They are present for the first time or as an exacerbation of established diseases. Diagnosis is difficult. It is very often impossible to identify the pathogen. The clinical symptoms in patients receiving HAART should be differentiated into IRS, ineffective HAART leading to the development of opportunistic infection, and drug toxicity.

AIDS-Related Opportunistic Infections↗

[Neuropsychiatric disorders in HCV-infected people--own observations].

UNLABELLED: Neuropsychiatric symptoms are commonly associated with chronic hepatitis C virus infection and its treatment. There are no Polish studies concerned this problem in patients during combination therapy (interferon and ribavirin). AIM: to examine the mood disorders an quality of life during the first 12 weeks of therapy. METHODS: The following research instruments were used: the Present State Examination (PSE), The Beck Depression Inventory, The Montgomery Asberg Depression Rating Scale, SF-36, Hamilton Depression Rating Scale. ALT, AST, GGT activity, HCV viral load and genotype, histological activity index of the liver was also measured. RESULTS: A group of 94 untreated patients (M=, K=) with hepatitis C was examined. 44 of them was examined secondly after 12 week of combination therapy. Depression disorders was observed in 4% pts before treatment and in 11% after 12 weeks therapy. In the group untreated patients there was two statistically significant correlations: between examined neuropsychiatric disorders and HCV viral load and necroinflammatory activity in the liver. CONCLUSIONS: The mood disorders are not so common in the patients with hepatitis C and could have biological etiology. The interferon based therapy increase the frequency and intensity of them.

Adult↗

[Experimental therapy in HCV infection].

PEGInterferon and ribavirin combination therapy is a gold standard in hepatitis C treatment. However it is not efficacious in all cases. Therefore, many studies are conducted to identifying additional drugs and therapeutic regimens, which might be more affordable. The progress in development of HCV culture systems (e.g.replicon) is crucial for successful therapeutic intervention in viral life-cycle (viral NS5B polymerase and NS3/4A protease inhibitors, antisense nucleotides, ribozymes, siRNA). Other classes of immunomodulatory/antiviral agents and new interferon formulation have also been considered for IFN-based therapy also. On the other hand immunomodulatory pathways are attractive target for novel anti-HCV therapy. Combination therapy targeting different aspects will be probably in the future successful option in hepatitis C treatment.

Antiviral Agents↗

[Pegylated interferon-alfa 2a with ribavirin in chronic viral hepatitis C (final report)].

UNLABELLED: We evaluated the efficacy and safety of peginterferon alfa-2a [40KD] (Peg-IFNalpha-2a) plus ribavirin in patients with chronic hepatitis C in an open-label programme in a routine clinical setting in Poland. Patients received Peg-IFNalpha-2a 180mg/week plus ribavirin 800-1200 mg/d for 48 weeks. Sustained virological response (SVR) was defined as undetectable HCV RNA (<50IU/mL) at the end of follow-up (week 72). 466 adults were enrolled. Most patients (87.3%) had genotype 1 infection. 440 subjects (94,4%) completed treatment. The overall SVR rate was 55.7%. A higher SVR rate was obtained in treatment-naïve patients (58.7%) than in relapsers (47.8%; p=0,048). SVR rates in genotype 1 and non-1 patients were 51.1% and 88.5%, respectively (p<0.001). There were significant higher SVR rates in patients with lower baseline fibrosis (p=0,01). There were no differences in SVRs by gender or viral load. Hemoglobin, leukocyte and neutrophil levels decreased significantly during treatment, but returned to baseline after the end of treatment. ALT levels decreased significantly during treatment in patients with and without an SVR. 38.4% of patients experienced adverse events like neutropenia, anemia, thrombocytopenia, and other. There was one death (severe thrombocytopenia). CONCLUSIONS: The overall SVR achieved in this predominantly genotype 1 population was 55.7%. SVR rates were significantly higher in treatment-naïve patients, those with non-1 genotypes, and in patients with lower baseline fibrosis scores.

Adult↗

[Hepatitis D virus superinfection--a rare cause of occupational disease].

The authors present a case of occupational HDV infection in a 38-year-old nurse, HBsAg carrier, injured by a needle contaminated with blood of a drug user infected with HIV, HBV and HCV. After 2 months she developed acute viral hepatitis. HBV, HCV, HIV, CMV, EBV and other non-viral liver diseases were excluded. Finally, based on the source of exposure with high probability of HDV infection, the patient's positive serological test for HDV, and the result of histological examination of the liver, the diagnosis of viral hepatitis type D was established. Our case report suggests the need to consider possible occupational HDV infection in certain circumstances as described above.

Adult↗

Prevention of hepatitis B recurrence after liver transplantation.

Over the last decade significant improvement in patient and graft survival has been observed after liver transplantation for hepatitis B virus (HBV)-related liver disease, mostly because of efficient prophylaxis against hepatitis B reinfection. This review discusses different approches in prevention of hepatitis B recurrence in liver recipients including new concepts as vaccination against hepatitis B after liver transplantation. Based on available data combined prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine is currently recommended prophylaxis for HBV recurrence after liver transplantation.

Antiviral Agents↗

[Hepatitis B virus genotypes and the response to lamivudine therapy].

Hepatitis B virus (HBV) can be classified into eight major genotypes (A-H) that have mainly a geographic distribution. The HBV genotype may influence disease progression, HBeAg seroconversion rates, response to antiviral treatment. The aim of study was to analyze the distribution and frequency of genotypes in patients with chronic hepatitis B. Response to lamivudine 100 mg daily therapy was examined in respect to genotype. Sixty six patients (45 (68,2%) male, 21 (31,8%) female) with chronic hepatits B were enrolled. HBV genotypes were assigned before treatment with INNO-LiPA HBV Genotyping, Innogenetics, N. V., Ghent assay, which is a line probe test based on the reverse hybridization principle. In baseline and after 12 months of treatment serological markers of HBV infection, alanine aminotransferase (ALT) activities and HBV DNA serum levels were tested. Patients with chronic hepatitis B were infected predominantly with genotype A. HBV genotype distribution was: 78,8% for genotype A, 13,6% for genotype D, 1,5% for mixed infection with genotypes A and D. Distribution of genotypes A and D was asymmetrically regardless of sex, HBeAg status, ALT and HBV DNA levels. Four (6,1%) specimens had indeterminate A results by LiPA. There were no significant differences between patients with genotypes A and D regarding age and sex. There were also no significant differences between these two groups regarding rates of HBeAg and anti-HBe positivity, ALT activity and viral load. Twenty months of lamivudine (100 mg daily) therapy resulted in significant decreases in serum HBV DNA and ALT activities in patients with genotype A as well as with genotype D. After 12 months of treatment there were no statistical differences in HBeAg seroconversion rates, ALT activities, viral loads, frequency of HBeAg and anti-HBe between genotypes A and D.

Adult↗

[Peginterferon alpha-2b in patients with chronic hepatitis C].

150 adult patients were assigned pegylated interferon alpha-2b (once weekly 1.5 microg/kg) plus ribavirin (800-1200 mg depending on bodyweight). The treatment lasted 52 weeks and was completed by 139 persons (92.7%). Because of adverse events the treatment was interrupted in 7 persons, 4 other persons resigned. Periodical reduction of pegylated interferon doses was necessary in 19% and the reduction of ribavirin in 21% of patients. Six months after the completion of treatment HCV-RNA was negative in 82 (59%) patients. Neither hepatitis C virus genotype, nor viremia was marked in the study. The negative correlation between the degree of fibrosis in the liver tissue and the results of sustained virological response was stated. Degree of inflammation at liver tissue, sex, age over and less than 40 years did not correlate with the final virological results. The recurrence of infection happened at 7% of the treated persons (negative HCV-RNA directly after the treatment--positive 6 months after the completion). During the treatment period, and comparison with the results obtained before its implementation, statistically significantly decreased: hemoglobin concentration, the number of leukocytes, granulocytes and thrombocytes. They returned to the referential values half a year after the completion of treatment. The activity of enzymes (AIAT, AspAT, GGTP) was decreasing statistically significantly since the first weeks of the treatment till the end and remained significantly lower after 6 months. In both sexes statistically significant reduction of bodyweight was stated, while it increased during the six months after the completion of treatment. Adverse events, which mostly were mild and were not the cause of interruption of treatment, were numerous and occurred at different frequency, in the range from over 50% (flu-like) to 0.7%.

Adult↗

[Contemporary opinions on the clinical symptoms, diagnosis and treatment of primary HIV infection].

Primary HIV infection (PHI) includes period between HIV infection and occurrence of anti-HIV antibodies. It is characterized by a high viral load, transient decrease of CD4+ T cell count, high infectivity and, what is very important, lack of anti-HIV antibodies. During PHI acute retroviral disease may occur with a lot of non-characteristic symptoms. The patients (pts) visit general practitioners and influenza-like infections or other viral infections are recognized. The additional reason of lack of proper diagnosis and the delay in diagnosis of HIV infection is negative result of anti-HIV antibodies. That is why the HIV infection is usually diagnosed very late. Patients unconscious of their HIV infection may be a source of infection for other people. Opinions concerning management of PHI are different and are discussed in the paper. The purpose of the paper was to present the problem of primary HIV infection to the doctors of different specialties, who should think about PHI in pts with risky behaviours for HIV infection or presenting symptoms resembling acute retroviral disease.

AIDS Serodiagnosis↗

[Epidemiological, clinical, immunological and virological characteristics of HIV-1 infected patients at the moment of initiation of antiretroviral therapy].

OBJECTIVE: The aim of the study was epidemiological, immunological and virological analysis of the cohort of the HIV-1 infected patients (pts) who had started highly active antiretroviral therapy (HAART). METHODS: Retrospective analysis of pts. data. RESULTS: 138 pts., mainly men, had started HAART since January 1996 till December 2000. Risk groups for HIV infection were as follows: IVDU: 63.8%, heterosexual: 23.9%, homosexual: 11.6%. 34% of pts. fulfilled criteria of initiating HAART already at the time of HIV-1 infection diagnosis. In 30.4% pts. 63 AIDS defining illnesses were diagnosed before HAART. We observed a very advanced HIV infection in our pts. at the time of HAART initiation (61.2% pts, with CD4 T cells count < 200/mm3; 58% pts. with HIV RNA level > 100,000 copies/mL). During HAART in 15.2% pts. 24 AIDS defining illnesses were recognized (in 7 cases it was reactivation of previous opportunistic infection, diagnosed before treatment). CONCLUSIONS: Our observations indicate that HIV infection in analysed group of pts. was diagnosed very late, in advanced stages of the disease. Most of our pts. were young IVDUs. Factors mentioned above had negative influence on the efficacy and tolerability of HAART.

Acquired Immunodeficiency Syndrome↗

[Comparison of two commercial molecular assays for quantitative measurement of hepatitis B viral DNA].

The detection and quantification of hepatitis B virus (HBV) genomes appear to be the most reliable method for monitoring HBV infection and assessing responses to antiviral treatment. For quantitative determination of HBV viremia molecular biology-based assays are used. The aim of this study was to compare and evaluate the performance of two HBV DNA detection and quantification commercial assays: hybrid-capture Digene Hybrid Capture HBV DNA assays and based on competitive polymerase chain reaction (PCR) Cobas Amplicor HBV Monitor Roche Diagnostics. Reproducibility, linearity, sensitivity were determined with 2-fold dilution series of high-titers samples and with 113 sera samples from patients with chronic HBV infection. Within-run and between-run coefficients of variation ranged from 2.4-9.7% for hybrid-capture and from 3.7-15% for PCR-based Monitor. The hybrid-capture and PCR Monitor assays appeared to be linear throughout their range of quantification: 5-2000 pg/ml and 2 x 10(2)-2 x 10(5) copies/ml respectively. The HBV DNA units used in the two assays were not comparable. Hybrid-capture and Monitor gave concordant results with 87 (82.1%) of 106 samples. The assays were both positive with 79 (74.5%) samples and were negative in 7 (7.5%) cases. Hybrid-capture and Monitor gave discordant results in 17 (17.9%) cases. The Monitor Assay was positive in 13 (61.9%) of the 21 samples negative in hybrid-capture. The competitive PCR-based Monitor assay appear to be significantly more sensitive but slightly less reproducible than the hybrid-capture. In the group of patients with seroconversion to anti-HBe PCR method should be used for measurement of viral load. In the presence of HBe antigen concentration of HBV DNA may be tested by hybrid-capture assay. Also these two assays may be used in complementary fashion in the management of HBV infected patients. It seems reasonable to use a hybrid-capture assay first, because its linear range of quantification is extended to high values and to use Monitor for samples that are negative in hybrid capture, because, its significantly higher sensitivity. However the lack of standardization among the assays makes it difficult to compare the results.

Biological Assay↗

[Epidemiology of occupational infectious diseases in health care workers].

BACKGROUND: Despite continuous progress in medicine and improvement of quality of work, occupational diseases are still a serious problem. During the last few years, 5000 to 12,000 cases of occupational diseases were annually registered in Poland. Among them, infectious diseases still occupy the third place. The aim of the study was to carry out an epidemiological analysis of occupational infectious diseases identified in health care workers of the Wrocław region in 1990-2002. MATERIALS AND METHODS: Information included in occupational disease identification cards was used as a basis for the study group selection. The form provided data on workplaces with exposure to agents responsible for generation of occupational diseases. Decisions on identification of occupational diseases in workers employed in EKD sections (code 85) were also taken into account. RESULTS: During last years, 136-300 cases of occupational diseases in health care workers were annually diagnosed in the Wrocław region, and infectious diseases made 10-30% of this number. In this group of diseases, viral hepatitis and tuberculosis were most frequent (45-82%). In 1990-2000, viral hepatitis was identified as an occupational disease in 323 health care workers; nurses formed the major group (195) followed by doctors (39) and lab workers (30). Recently, epidemiological situation of occupational infectious diseases has improved. From 1989, the incidence of occupational viral hepatitis in health care workers is on the systematic decrease (only 17 cases in 1994). Undoubtedly, the introduction of obligatory vaccination against HBV among health care workers has greatly contributed to this improvement. CONCLUSIONS: It is found that hepatitis B virus (HBV) is the major factor responsible for infections in professional health care workers. The decrease in HBV infections correlates with a growing proportion of the vaccinated personnel. It should be stressed that infections with HCV are on the increase in this occupational group.

Communicable Diseases↗

[Autoimmune liver diseases and overlap syndromes--overview of past and present reports].

Autoimmune liver diseases are unique among other liver diseases mainly for its unknown pathogenesis, treatment and prognosis. Within their natural course strong correlation between clinical view and serologic markers (autoimmune hepatitis, primary biliary cirrhosis) or X-ray image abnormalities (primary sclerocholangitis) are observed. Significant diagnostic progress, recently seen, revealed major discrepancies in diagnosing and management of classic types of the diseases, suggesting co-association of their symptoms. This review presents former and most up-to-date reports of such cases in terms of overlap syndromes.

Autoimmune Diseases↗

Solid organ transplantation and HIV infection.

HIV infection has been traditionally considered to be an absolute contraindication for solid organ transplantation. Recent advances in HIV treatment, as highly active antiretroviral therapy (HAART), significantly reduced HIV-related mortality and morbidity. At the same time the number of HIV-infected patients with end-stage organ diseases constantly increased. Current data describing solid organ transplantation in HIV-infected patients demonstrated comparable outcome to that in the HIV-negative population. In light of this, solid organ transplantation should be considered as a treatment option for selected HIV-positive patients with end-stage organ disease.

AIDS-Related Opportunistic Infections↗