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Biomedical subjects

S Esser

Publications and source records attributed to S Esser.

At least 19 recordsLinked to original sources
PubMed2006

[Antiviral treatment regimens].

The availability and use of effective antiretroviral combination therapies has dramatically decreased the morbidity and mortality of HIV infection. Almost complete suppression of viral replication by antiretroviral therapy prevents disease progression and development of resistance, as well as leading to both regression of HIV-associated symptoms and clinically relevant immune reconstitution. More than 20 antiretroviral substances in four classes have been approved. As a result of the broad therapeutic options, HIV infection can be better treated. Although a high number of combinations can be conceived, only a small number is actually applicable. The decisions to start, monitor and change therapy have become even more difficult. The indication for treatment, the selection of the most suitable therapy for an individual, the counseling of the patient, and the monitoring of the success of treatment demand a high level of knowledge and experience. Virologic failures of modern antiretroviral therapy regimens are rare in adherent patients.

Anti-HIV Agents↗
PubMed2004

Evolution of purely infratentorial PML under HAART--negative outcome under rapid immune reconstitution.

Progressive multifocal leukoencephalopathy (PML) caused by the polyomavirus JC is a well-recognised complication of AIDS. Purely infratentorial manifestations are rare. Introduction of highly active antiretroviral therapy (HAART) has been associated with a reduction in morbidity and an improvement in overall survival among HIV-infected individuals. Recently, several reports have described adverse events in patients with PML who begin HAART and show evidence for immune reconstitution. We describe the clinical course of two patients with PML with purely infratentorial manifestation, whose clinical course deteriorated despite the successful introduction of HAART. Possible underlying immunological mechanisms are discussed.

Adult↗
PubMed2004

Cardiovascular risk factors and probability for cardiovascular events in HIV-infected patients - part III: age differences.

OBJECTIVE: In recent years, concerns have been growing about an elevated rate of cardiovascular diseases in HIV-infected patients due to side effects of antiretroviral therapy. The present study analyses the cardiovascular risk profile and the probability of cardiovascular events with regard to the age of HIV-infected patients. METHODS: Cardiovascular risk factors of 309 HIV-infected adults were analysed. Patients were divided into four groups: 18-30 years (group 1), 31-40 years (group 2), 41-50 years (group 3), > 50 years (group 4). Overall 10-years probability for cardiovascular events was evaluated by the Framingham algorithm. RESULTS: Differences between the groups were detected in cardiovascular risk factors including changes in lipid- and glucose metabolism. Lipid values increased with elevated age, such as total cholesterol concentration (Mean +/- SEM in group 1 vs. group 4: 4.71 +/- 0.20 to 6.36 +/- 0.21 mmol/L, p < 0.05), LDL-cholesterol concentration (2.86 +/- 0.17 vs. 4.17 +/- 0.21 mmol/L, p < 0.05) and triglyceride concentration (1.56 +/- 0.14 vs. 3.48 +/- 0.40 mmol/L, p < 0.05). HDL-cholesterol concentration did not show a significant difference (1.15 +/- 0.03 mmol/L). Glucose concentration increased with elevated age in HIV-infected patients (5.28 +/- 0.19 vs. 6.46 +/- 0.24 mmHg, p < 0.05), but there was no significant difference in HbA1c - concentration, blood pressure and smoking rate between the groups. The overall 10-years probability for cardiovascular events was higher in group 1 (median: 1.9%) than in group 4 (20.5%; p < 0.01). CONCLUSIONS: The risk of cardiovascular events is related to the age in HIV-infected patients. Therefore, an increased duration of life due to a more effective antiretroviral therapy will have a significant impact on the rate of cardiovascular events in this patient population. In the future, further increase of cardiovascular events in HIV-infected patients may be expected.

Adolescent↗
PubMed2004

[Bacterial colonization of chronic wounds. Studies on outpatients in a university dermatology clinic with special consideration of ORSA].

In this retrospective investigation, we documented the bacterial colonization of 79 patients with chronic wounds, who had been treated between January 2002 and May 2003 in an outpatient wound healing clinic of a university dermatology program. We isolated 106 facultative pathogenic bacterial strains of which 56 were Staphylococcus aureus, 19 Pseudomonas aeruginosa, 11 Escherichia coli, 4 Proteus mirabilis, 4 Enterobacter cloacae, 2 Serratia marcescens, 2 Streptococcus group G und 8 further species. 68 of these bacterial strains were gram-positive and 46 gram-negative. Moreover we identified one patient with Candida parapsilosis. Therefore, 70.8% of all patients showed Staphylococcus aureus in their chronic wounds. Determination of the specific resistances showed 17 patients to be colonized with oxacillin- resistant Staphylococcus aureus (ORSA) strain; this corresponds to 21.5% of all patients. Consequently, 30.4% of all Staphylococcus aureus isolates were ORSA strains. All of the ORSA isolates were sensitive to vancomycin. Sensitivity to tetracycline was documented in 15, to amikacin in 13, to clindamycin in 7, to gentamicin and erythromycin in 6 of the ORSA-positive patients. In the case of trimethoprim/sulfamethoxazole, 10 were sensitive and 3 were intermediate in sensitivity. Beside the obligate resistance to oxacillin, penicillin G, ampicillin, cefuroxime and imipenem, none of the ORSA was sensitive to ofloxacin. The results of our investigations demonstrate the actual spectrum of bacterial colonization in chronic wounds of patients in an university dermatologic wound clinic and underline the growing problem of ORSA.

Aged↗
PubMed2004

Highly sensitive biosafety model for stem-cell-derived grafts.

BACKGROUND: The recent success in the derivation of differentiated cell types from stem cells has raised prospects for the application of regenerative cell therapy. In particular, embryonic stem cells are attractive sources for cell transplantation, due to their immortality and rapid growth. These cells, however, also possess tumorigenic properties, which raises serious safety concerns and makes biosafety testing mandatory. Our goal was to establish a highly sensitive animal model for testing the proliferative potential of stem-cell grafts. METHODS: BALB/c nude mice received cell grafts of non-neoplastic MRC-5 cells containing defined numbers of mouse embryonic stem cells. We either injected 1 million viable cells into the kidney capsule, or mixed 2 million cells with Matrigel for s.c. transplantation. To analyze the possible impact of an intact immune response on tumor development, we also transplanted the cells into immunocompetent mice. Animals were sacrificed when the tumors became >1 cm and were analyzed in detail. RESULTS: The nude mouse model reproducibly allowed detection of 20 tumorigenic cells, and even as few as 2 ES cells were found to form teratoma. Interestingly, the administration of cell grafts at two different application sites resulted in different growth kinetics and tumor phenotypes. The highest level of sensitivity (100% detection of 20 tumorigenic ES cells) was achieved by s.c. injection of cells mixed with Matrigel. The influence of the immune system on tumor-cell development was demonstrated by a higher tumor rate of transplants in immunodeficient nude mice compared with immunocompetent mice. DISCUSSION: We have established a reliable animal model for routine assessment of the biosafety profile of stem-cell-derived cell transplants. This model will facilitate the generation of homogenous non-tumorigenic cell populations, and will help to integrate standardized safety systems into the application of stem-cell-derived grafts for clinical purposes.

Animals↗
PubMed2003

[Screening and therapy of anal intraepithelial neoplasia (AIN) and anal carcinoma in patients with HIV-infection].

Anal intraepithelial neoplasia (AIN) is a potential precursor of invasive anal carcinoma. Introduction of highly active antiretroviral therapy (HAART) in the treatment of HIV infection substantially reduced the incidence of some diseases associated with opportunistic viral infections. However, the incidence of AIN is reported to increase and HAART seems to have only little impact on the regression or progression of AIN. Paradoxically, improvement of survival in the HAART era results in an increased risk of anal cancer. The incidence of anal carcinoma amongst homosexual men is substantially higher compared to the normal population (35/100.000). This incidence is similar to the incidence of cervical cancer before screening for CIN with cervical cytology. Recent data suggest that the incidence of AIN and anal cancer is even higher among HIV-infected individuals. Both cancer entities share biologic similarities, including the association with human papillomavirus infection (HPV). Screening for CIN with cervical cytology and early treatment has resulted in a significant decline in the incidence of cervical carcinoma. Like cervical cancer, anal carcinoma may be preventable through identification and treatment of its precursors. Future efforts should focus on a screening protocol, training of clinicians in the diagnosis and treatment of AIN and anal carcinoma, and novel approaches to treatment of these lesions. This screening protocol could help to reduce anal cancer in HIV-infection as well as save limited resources in health care system.

Antiretroviral Therapy, Highly Active↗
PubMed2003

[Pathogenetic significance of methicillin resistant Staphylococcus aureus (MRSA) in chronic wounds].

The colonisation and infection with methicillin-resistant staphylococcus aureus (MRSA) represent an interdisciplinary problem especially in the treatment of chronic wounds. To prevent medical wound-healing centres of becoming vectors for further epidemics it makes sense to take regular bacterial smears of all patients with chronic wounds to identify, isolate and treat patients with MRSA colonisation or infection. Especially infections should only be treated after microbiological diagnostics had been done to allow systemic treatment with antibiotics in accordance with the specific resistances. Otherwise the uncritical use of broad-spectrum- or reserve-antibiotics supports the critical development of further resistances.

Bacteriological Techniques↗
PubMed2002

[Treatment of methicillin-resistant Staphylococcus aureus (MRSA) as part of biosurgical management of a chronic leg ulcer].

Colonization with methicillin-resistant Staphylococcus aureus (MRSA) strains is an increasing problem in the treatment of wounds. Only a very limited repertoire of effective treatment strategies is available, especially for outpatient care. We successfully treated a chronic leg ulcer colonized with MRSA on an ambulatory basis, using larvae of the common greenbottle fly Lucilia sericata. Whereas the proteases secreted by Lucilia sericata may lead to efficient selective necrolysis, the phenylacetate and phenylacetataldehyde may exert antimicrobial effects. Treatment with Lucilia sericata represents an effective and inexpensive treatment strategy of chronic wounds, especially when colonized with MRSA Due to the low acceptance by patients and medical stuff, it is not often employed.

Aged↗
PubMed2002

[Atherosclerosis in HIV-positive patients].

Worldwide, human immunodeficiency virus (HIV) infection is one of the main health subjects. Even, the human immunodeficiency virus primarily effects the immune system, HIV infection also has an impact on other organs. Cardiovascular manifestations in HIV-infected patients could occur by the HI-virus itself or by opportunistic infections. Reports of myocardial infarction in young HIV-infected patients, who received protease inhibitors, have raised concerns about premature arteriosclerosis and coronary artery disease in this population. In the pre-protease inhibitor era, autopsy reports were the first to describe an association between coronary artery disease and HIV infection. Long-term antiretroviral therapy, including protease inhibitors, significantly reduced mortality, morbidity and revolutionized the care of HIV-infected patients. However, class-specific metabolic side effects, such as elevated total cholesterol and triglyceride levels and insulin resistance, have been described. These metabolic alterations of antiretroviral therapy impair the cardiovascular risk profile of HIV-infected patients. Even epidemiological studies found no significant effect of antiretroviral treatment type on coronary heart disease or myocardial infarction, an increase of arteriosclerosis in HIV-infected patients is suspected. Recent results of autopsy studies and analyses of endothelial function in patients with HIV infection described an effect of HIV and antiretroviral therapy on premature arteriosclerosis. The present article gives an overview about arteriosclerosis and coronary events in HIV-infected patients and the impact of antiretroviral therapy.

Antiretroviral Therapy, Highly Active↗
PubMed2001

The role of sentinel lymph node mapping in staging of colon and rectal cancer.

PURPOSE: Nodal metastasis is the best predictor of survival for patients with colon cancer. Statistical models based on random distribution of positive lymph nodes suggest that to correctly classify nodal status with 95 percent confidence, 20 nodes are needed for T1 lesions, 17 nodes for T2, and 15 nodes for T3. The mean number of nodes identified in American patients is 8, suggesting that they might not be accurately staged. Patients in our tumor registry staged as "node-negative" had a short survival when they had < or =10 lymph nodes evaluated when compared with patients with >10 lymph nodes evaluated (p < 0.01). We hypothesized that the use of sentinel lymph node may assist in the staging of colon cancer. METHODS: Thirty-eight consecutive patients with colon lesions were prospectively enrolled into this trial between February 1998 and November 1999. Thirty-one patients met criteria for analysis. During surgery, Lymphazurin blue dye was injected subserosally into the area around the tumor. Routine nodal evaluation, with extra cuts of all sentinel nodes, was undertaken. RESULTS: At least one sentinel lymph node was found in 18 of 31 patients (58 percent). Sensitivity of 67 percent, specificity and positive predictive value of 100 percent, and negative predictive value of 94 percent were found when sentinel lymph nodes were identified. In 2 of these 18 patients, the sentinel lymph node was the only positive lymph node found. CONCLUSIONS: Application of the sentinel lymph node technique to colon cancer may make it easier to identify lymph nodes most likely to contain metastatic disease, potentially "down-staging" more patients. This may have implications in postoperative care.

Adolescent↗
PubMed2001

Long-term chemotherapy of HIV-associated Kaposi's sarcoma with liposomal doxorubicin.

The aim of this study was to examine the outcome, adverse events and clinical complications of long-term chemotherapy with pegylated liposomal doxorubicin (PegLiposomal DOX) for human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS) in the pre-highly active antiretroviral therapy (HAART) era. A phase II study over a 4-year period in a tertiary care university hospital was carried out. 52 acquired immunodeficiency syndrome (AIDS)-patients with advanced KS received long-term chemotherapy (71+/-51 weeks) with a mean of 22.8+/-18.2 cycles and a mean cumulative liposomal doxorubicin dose of 456+/-364 mg/m(2) (120-1040 mg/m(2)). Tumour burden, duration and dosage of PegLiposomal DOX, adverse events, opportunistic infections, immunological parameters and HIV load were measured. A complete (10%) or partial response (56%) was achieved while on chemotherapy. 10 patients (19%) showed stable disease. Tumour progression was observed in 8 patients (15%). Importantly, chemotherapy with PegLiposomal DOX was also successful after previous cytostatic therapy with bleomycin and vincristine. The most common adverse events included leucopenia, neutropenia, anaemia, and increased liver function tests. 34 patients (65%) developed new opportunistic infections and 29 patients (56%) died during the study period. To conclude, pegylated liposomal doxorubicin is a safe and effective drug for long-term chemotherapy of advanced (AIDS) KS without adverse effects on CD4 cell counts and HIV viral load.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Expression of wild-type and noncleavable Fas ligand by tetracycline-regulated adenoviral vectors to limit intimal hyperplasia in vascular lesions.

Proliferation of vascular smooth muscle cells (VSMCs) and the infiltration of T cells and macrophages into vessel wall are considered to be important for intimal lesion formation after balloon angioplasty. Previous studies have shown that Fas ligand (FasL) gene transfer to balloon-injured vessels inhibits lesion formation by killing both proliferating VSMCs and infiltrating inflammatory cells. Here, we describe the construction and utility of a binary, tetracycline-regulated adenovirus system that provides controlled transgene expression in vitro and in vivo. In this system, optimal transgene expression required cotransfection with an adenovirus encoding the tetracycline-dependent trans-activator (rtTA) and induction with doxycycline hydrochloride (DOX), an analog of tetracycline. Using this system, adenovirus constructs were designed that allow regulated expression of wild-type FasL and a noncleavable mutant of FasL (FasL-NC). Transduction of FasL and FasL-NC induced similar extents of apoptosis in proliferating VSMCs in vitro in a manner that was dependent on the doses of the rtTA adenovirus and the presence of DOX in the medium. Furthermore, inhibition of intimal hyperplasia in injured carotid arteries by FasL or FasL-NC transduction was also dependent on cotransfection with the rtTA adenovirus and administration of DOX by subcutaneous injection. In contrast to wild-type FasL, transduction of FasL-NC did not result in the production of soluble (cleaved) FasL in the medium of infected cells in vitro, or in the serum of rats after local gene transfer to carotid arteries. In conclusion, this binary tetracycline-inducible adenovirus system may allow for safer delivery of cytotoxic genes for therapeutic purposes.

Adenoviridae↗
PubMed2000

Self-administered topical 5% imiquimod for the treatment of common warts and molluscum contagiosum.

BACKGROUND: Despite numerous therapeutic options the treatment of common warts and molluscum contagiosum remains unsatisfactory for both patients and physicians. Imiquimod, a novel topical immune response modifier, has been successfully used for the treatment of external anogenital warts. OBJECTIVES: We aimed to evaluate the safety, tolerance and efficacy of imiquimod for the treatment of common cutaneous warts and mollusca that were resistant to previous therapeutic interventions. METHODS: Imiquimod 5% cream was self-applied by the patients to the warts or mollusca once daily for 5 days per week and left in place overnight. Assessment for response and the occurrence of side-effects was performed every 4 weeks until clinical cure or up to a maximum of 16 weeks. RESULTS: Twenty-eight of 50 (56%) patients with warts achieved a total clearance (n = 15; 30%) or a > 50% reduction in wart size (n = 13; 26%) after a mean treatment period of 9.2 weeks. Twelve of 15 (80%) patients with mollusca achieved a total clearance (n = 8; 53%) or a > 50% reduction in molluscum size (n = 4; 27%). There was no difference in response with regard to gender, human immunodeficiency virus serostatus or atopic predisposition. CONCLUSIONS: Patient-applied 5% imiquimod cream holds promise as an effective treatment of common warts and mollusca in a difficult-to-treat patient population.

Adolescent↗
PubMed2000

Incidence and prevalence of neurological disorders associated with HIV since the introduction of highly active antiretroviral therapy (HAART).

OBJECTIVE: To determine the change of incidence and prevalence of neurological disorders caused by the human immunodeficiency virus (HIV) and opportunistic infections in HIV positive patients under treatment since the introduction of highly active antiretroviral therapy (HAART). METHODS: The data of all HIV infected patients were retrospectively analysed, who were examined in the HIV outpatients clinic of the neurological department of the University Clinic Essen between 1995 and 1998 (n=563, total number of visits=735). Data from identified patients were divided into two groups according to the time of examination from 1995 to 1996 (334 visits) and from 1997 to 1998 (401 visits). The incidence and prevalence of neurological disorders were statistically compared between both time intervals. RESULTS: Significantly more patients received HAART in 1997-8 (p<0. 001) and mean CD4+ cell count was significantly higher in 1997-8 (p<0.001). The prevalence of HIV associated dementia and HIV associated polyneuropathy were significantly lower in 1997-8 (both: p=0.02) and the incidence of toxoplasma encephalitis decreased from 5.7% in 1995-6 to 2.2% in 1997-8 (p=0.015). Based on the small number of patients significant changes in HIV associated myopathy, progressive multifocal leukoencephalopathy, cryptoccocal meningitis, and cytomegalovirus-encephalitis could not be detected. CONCLUSION: The prevalence of the most frequent HIV associated neurological disorders and incidence of toxoplasma encephalitis decreased since the introduction of HAART. This may be due to the improvement of immunostatus by HAART as demonstrated by the higher CD4+ cell count in the later time interval. Direct antiretroviral effects within the nervous system may be considered causative as well. The prevalence and incidence of HIV associated neurological disorders and opportunistic CNS infections decreased after introduction of HAART.

Adult↗
PubMed1998

Randomized, controlled phase II trial of subcutaneous interleukin-2 in combination with highly active antiretroviral therapy (HAART) in HIV patients.

OBJECTIVE: To determine the immunological, virological and clinical effects of subcutaneous IL-2 in 44 HIV-patients in conjunction with pre-existing tri-therapy (zidovudine, 3TC, saquinavir). DESIGN: Partially randomized, controlled, prospective trial. SETTING: Single center study at tertiary care center. PATIENTS: Sixty four patients (CD4 count 200-500 x 10(6)/l). INTERVENTION: Fourty four patients were randomized to receive 5-day cycles of IL-2 (9 Mio IU/d) every 6 weeks (Group A) or whenever the CD4 cell count dropped below the 1.25-fold of baseline (Group B), whereas 20 control patients received the same HAART without IL-2. OUTCOME MEASURES: The optimal individual treatment interval and the immunological and virological effects of subcutaneously administered IL-2 were analysed. Importantly, the level of cellular in vivo immunity and the frequency of dermatological marker diseases and infectious complications were assessed. RESULTS: IL-2 was well tolerated although fever, influenza-like symptoms and indurated injection sites were commonly encountered. After 1 year of IL-2, there was a median increase of more than 100 x 10(6)/l CD4 cells in both IL-2 groups in contrast to the controls (P < 0.01, 0.01 and not significant). The median HIV load did not increase either in plasma or in lymph nodes. Lymphocyte activation decreased as assessed by MHC class II (P < 0.001), CD25 (P < 0.001) and CD38 expression (P < 0.005). Although delayed type hypersensitivity against common recall antigens increased in both IL-2 groups, it did not reach statistical significance. However, it is of note, that in 7 of 11 (63.6%) patients delayed type hypersensitivity against recombinant HIV antigens improved significantly. Whereas there was no opportunistic infection in either IL-2 group, three cases of Kaposi's sarcoma occurred in the controls. Dermatological indicator diseases (thrush, condyloma, herpes simplex) were found to occur more frequently in the control group. CONCLUSIONS: Subcutaneous IL-2 in addition to HAART was safe and led to sustained qualitative and quantitative immunological improvements in the majority of patients. Individualisation of therapy intervals further improved the efficacy and tolerance of IL-2.

Adult↗