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1.
J Eur Acad Dermatol Venereol ; 36(11): 2181-2189, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35796163

ABSTRACT

BACKGROUND: Bullous pemphigoid (BP), the by far most frequent autoimmune blistering skin disease (AIBD), is immunopathologically characterized by autoantibodies against the two hemidesmosomal proteins BP180 (collagen type XVII) and BP230 (BPAG1 or dystonin). Several comorbidities and potentially disease-inducing medication have been described in BP, yet a systematic analysis of these clinically relevant findings and autoantibody reactivities has not been performed. OBJECTIVE: To determine associations of autoantibody reactivities with comorbidities and concomitant medication. METHODS: In this prospective multicenter study, 499 patients diagnosed with BP in 16 European referral centers were included. The relation between anti-BP180 NC16A and anti-BP230 IgG ELISA values at the time of diagnosis as well as comorbidities and concomitant medication collected by a standardized form were analysed. RESULTS: An association between higher serum anti-BP180 reactivity and neuropsychiatric but not atopic and metabolic disorders was observed as well as with the use of insulin or antipsychotics but not with dipeptidyl peptidase-4 (DPP4) inhibitors, inhibitors of platelet aggregation and L-thyroxine. The use of DPP4 inhibitors was associated with less anti-BP180 and anti-BP230 reactivity compared with BP patients without these drugs. This finding was even more pronounced when compared with diabetic BP patients without DPP4 inhibitors. Associations between anti-BP180 and anti-BP230 reactivities were also found in patients using insulin and antipsychotics, respectively, compared with patients without this medication, but not for the use of inhibitors of platelet aggregation, and L-thyroxine. CONCLUSION: Taken together, these data imply a relation between autoantibody reactivities at the time of diagnosis and both neuropsychiatric comorbidities as well as distinct concomitant medication suggesting a link between the pathological immune mechanisms and clinical conditions that precede the clinically overt AIBD.


Subject(s)
Antipsychotic Agents , Dipeptidyl-Peptidase IV Inhibitors , Insulins , Pemphigoid, Bullous , Serum Sickness , Antipsychotic Agents/adverse effects , Autoantibodies , Autoantigens , Blister , Dipeptidyl Peptidase 4/therapeutic use , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Dystonin , Humans , Hypoglycemic Agents/therapeutic use , Immunoglobulin G , Insulins/therapeutic use , Non-Fibrillar Collagens , Prospective Studies , Thyroxine/therapeutic use
2.
Life Sci ; 268: 118936, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33421523

ABSTRACT

AIMS: During oxidative stress mitochondria become the main source of endogenous reactive oxygen species (ROS) production. In the present study, we aimed to clarify the effects of pharmacological PARP-1 inhibition on mitochondrial function and quality control processes. MAIN METHODS: L-2286, a quinazoline-derivative PARP inhibitor, protects against cardiovascular remodeling and heart failure by favorable modulation of signaling routes. We examined the effects of PARP-1 inhibition on mitochondrial quality control processes and function in vivo and in vitro. Spontaneously hypertensive rats (SHRs) were treated with L-2286 or placebo. In the in vitro model, 150 µM H2O2 stress was applied on neonatal rat cardiomyocytes (NRCM). KEY FINDINGS: PARP-inhibition prevented the development of left ventricular hypertrophy in SHRs. The interfibrillar mitochondrial network were less fragmented, the average mitochondrial size was bigger and showed higher cristae density compared to untreated SHRs. Dynamin related protein 1 (Drp1) translocation and therefore the fission of mitochondria was inhibited by L-2286 treatment. Moreover, L-2286 treatment increased the amount of fusion proteins (Opa1, Mfn2), thus preserving structural stability. PARP-inhibition also preserved the mitochondrial genome integrity. In addition, the mitochondrial biogenesis was also enhanced due to L-2286 treatment, leading to an overall increase in the ATP production and improvement in survival of stressed cells. SIGNIFICANCE: Our results suggest that the modulation of mitochondrial dynamics and biogenesis can be a promising therapeutical target in hypertension-induced myocardial remodeling and heart failure.


Subject(s)
Hypertension/physiopathology , Hypertrophy, Left Ventricular/drug therapy , Mitochondria, Heart/drug effects , Myocytes, Cardiac/drug effects , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Animals , Cells, Cultured , Citrate (si)-Synthase/metabolism , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism , Electrocardiography , Glutathione/metabolism , Hypertrophy, Left Ventricular/etiology , Male , Membrane Potential, Mitochondrial/drug effects , Mitochondria, Heart/metabolism , Mitochondria, Heart/pathology , Mitochondria, Heart/ultrastructure , Mitochondrial Proteins/metabolism , Myocytes, Cardiac/pathology , Natriuretic Peptide, Brain/blood , Piperidines/pharmacology , Quinazolines/pharmacology , Rats, Inbred SHR , Rats, Wistar
4.
Hautarzt ; 71(5): 374-379, 2020 May.
Article in German | MEDLINE | ID: mdl-32144440

ABSTRACT

BACKGROUND: According to the current scabies guideline, topical treatment with permethrin 5% cream is the first-line therapy of common scabies in Germany. However, in the course of growing incidence of scabies in recent years there have been increasing numbers of reports of reduced efficacy in standard therapy. OBJECTIVE: To establish a better understanding for the efficacy of scabies therapy under practice conditions, a survey focusing on the first-line therapy with permethrin was conducted in dermatological hospitals, outpatient clinics and dermatology practices. METHODS: The postal survey addressed all dermatologically active physicians in Germany and queried diagnostic methods, the individual initial treatment, the estimated efficacy of permethrin therapy, the frequency and reasons for therapy failures under permethrin and the therapeutic approach in case of failure of the initial therapy. RESULTS: The efficacy of permethrin was rated with 73% by 187 physicians. About 74% reported to treat initially with 5% permethrin cream. The most common reasons identified for treatment failure were application errors, lack of compliance and inadequate hygiene measures. Suspected diminished efficacy or development of resistance against permethrin and re-infestations were also mentioned. In the case of ineffectiveness of initial therapy, most clinicians opt for oral ivermectin, a repetition of permethrin therapy or a combination of both. CONCLUSION: Although there are localized reports of decreased effectiveness of permethrin therapy, results of this survey point towards a persisting high efficacy of first-line standard treatment of scabies with permethrin 5% cream in Germany.


Subject(s)
Antiparasitic Agents/therapeutic use , Scabies/drug therapy , Administration, Topical , Enzyme Inhibitors/therapeutic use , Germany/epidemiology , Humans , Insecticides , Permethrin , Scabies/diagnosis , Scabies/epidemiology , Scabies/pathology , Surveys and Questionnaires , Treatment Outcome
5.
Z Rheumatol ; 79(10): 1057-1066, 2020 Dec.
Article in German | MEDLINE | ID: mdl-32040755

ABSTRACT

BACKGROUND: Raynaud's phenomenon and the frequently ensuing digital ulcerations represent an early and very distressing symptom in patients with systemic sclerosis (scleroderma, SSc) causing significant limitations in the ability to work and quality of life. The use of vasoactive drugs (especially intravenous prostacyclin derivatives) is recommended to reduce the risk of hypoxic tissue damage up to the loss of fingers. METHODS: In order to obtain information about the current state of treatment of patients with prostacyclin derivatives in routine clinical life in Germany, a survey was conducted among the centers affiliated to the German Network for Systemic Scleroderma (DNSS). In addition, a separate patient survey was conducted by the schleroderma self-help group (Sklerodermie Selbsthilfe e. V.), which only covered the symptoms Raynaud's syndrome, digital ulcers and the use of intravenous prostacyclin derivatives. RESULTS: Of the 433 patients surveyed 56% stated that they had already been treated with prostacyclin derivatives (iloprost/alprostadil) because of their illness and symptoms. A total of 61% received the treatment for severe Raynaud's phenomenon and 39% for digital ulcerations. Most respondents not only experienced an improvement in Raynaud's phenomenon and digital ulcers but also a significant improvement of limitations in everyday life. They also needed significantly less outside help and absenteeism from work was much lower. CONCLUSION: Patients consistently reported a positive effect of treatment with prostacyclin derivatives on Raynaud's phenomenon, acral ulcerations, pain and daily restrictions and felt well and safely cared for during inpatient treatment. These positive effects in the patients' perceptions provide crucial information supporting and confirming the current European and international treatment recommendations.


Subject(s)
Epoprostenol , Raynaud Disease , Scleroderma, Systemic , Epoprostenol/analogs & derivatives , Epoprostenol/therapeutic use , Fingers/blood supply , Germany , Humans , Inpatients , Quality of Life , Raynaud Disease/diagnosis , Raynaud Disease/drug therapy , Raynaud Disease/epidemiology , Scleroderma, Systemic/complications , Scleroderma, Systemic/diagnosis , Scleroderma, Systemic/drug therapy , Skin/blood supply
6.
Hautarzt ; 71(1): 53-56, 2020 Jan.
Article in German | MEDLINE | ID: mdl-31236629

ABSTRACT

Wolf's isotopic response describes the eruption of a secondary, pathogenically independent skin disease within the borders of a primary, already healed skin disease. The exact mechanism is unknown, but the restriction to diseases with a known T­cell component in the pathogenesis suggests an involvement of persistent local immune activation. We report the case of an 87-year-old woman who developed bullous pemphigoid lesions within the boundaries of a previous, already healed herpes zoster C7-C8, which had been diagnosed clinically and treated 2 months previously. Histopathological examination revealed subepidermal blisters, and indirect immunofluorescence showed IgG antibodies against the basal membrane zone. Both BP 180 and BP 230 enzyme-linked immunoassays (ELISAs) were positive. Based on these findings, we diagnosed a bullous pemphigoid arising on the site of the already healed herpes zoster, linked by an isotopic response.


Subject(s)
Herpes Zoster , Pemphigoid, Bullous , Aged, 80 and over , Female , Herpes Zoster/complications , Humans , Pemphigoid, Bullous/complications , Skin
7.
Clin Exp Dermatol ; 43(3): 248-253, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29333745

ABSTRACT

BACKGROUND: Indirect immunofluorescence (IIF) microscopy on monkey oesophagus is an important assay for the diagnosis of bullous pemphigoid (BP). Its relatively low sensitivity (60-80%) may be partly due to insufficient detection of minor IgG subclasses. AIM: To determine the operating characteristics of an IgG subclass in IIF. METHODS: We designed a retrospective, dual-centre, controlled cohort study on sera from 64 BP sera that had been rated as false negatives by traditional IIF microscopy, and assessed circulating IgG1 , IgG3 and IgG4 autoantibodies. RESULTS: The sensitivities of IIF in detecting IgG1 , IgG3 , IgG4 and all three in combination were 45.3%, 18.8%, 32.8% and 48.4%, respectively. Specificities were > 97%. CONCLUSION: Detection of IgG subclass (especially IgG1 and IgG4 ) autoantibodies by IIF on monkey oesophagus can significantly improve diagnostic performance of IIF microscopy for diagnosis of BP.


Subject(s)
Fluorescent Antibody Technique, Indirect , Immunoglobulin G/classification , Pemphigoid, Bullous/immunology , Adult , Aged , Aged, 80 and over , Animals , Enzyme-Linked Immunosorbent Assay , Esophagus/immunology , False Negative Reactions , Female , Haplorhini , Humans , Immunoglobulin G/blood , Male , Middle Aged , Pemphigoid, Bullous/diagnosis , Retrospective Studies , Sensitivity and Specificity
8.
Hautarzt ; 67(10): 786-792, 2016 Oct.
Article in German | MEDLINE | ID: mdl-27576550

ABSTRACT

BACKGROUND: Mucous membranes are involved in many different inflammatory disorders. METHODS: We describe the clinical features, diagnostic workup, and therapy of inflammatory diseases of mucous membranes. RESULTS: The diagnostic workup is based on medical history, clinical manifestations, histopathology, and serology. Inadequate dental hygiene is one of the main pathogenetic factors. Treatment options depend on the diagnosis, underlying cause, and disease severity. Both local and systemic immunosuppressive or immunomodulatory strategies may be effective. CONCLUSIONS: The diagnostic and therapeutic management of inflammatory mucous membrane disorders is usually more difficult than that of skin diseases and requires interdisciplinary cooperation.


Subject(s)
Immunosuppressive Agents/therapeutic use , Mouth Mucosa/pathology , Mucous Membrane/pathology , Pemphigoid, Benign Mucous Membrane/diagnosis , Pemphigoid, Benign Mucous Membrane/drug therapy , Stomatitis/diagnosis , Stomatitis/drug therapy , Diagnosis, Differential , Evidence-Based Medicine , Humans , Immunologic Factors/therapeutic use , Treatment Outcome
9.
Hautarzt ; 66(8): 583-8, 2015 Aug.
Article in German | MEDLINE | ID: mdl-26077944

ABSTRACT

BACKGROUND: The incidence and thereby also the relevance of pemphigoid diseases have significantly increased in elderly patients. METHODS: The clinical features, diagnostic workup, and therapy of pemphigoid diseases based on the recently published German guidelines and expert opinions are described. RESULTS: The diagnosis is based on medical history, clinical manifestations, histopathology, and autoimmune serology. Treatment options depend on the diagnosis and disease severity. Both local and systemic immunosuppressive or immunomodulatory strategies have been proven to be effective. CONCLUSIONS: Chronic, itchy, inflammatory skin disorders in elderly patients are generally suspicious for pemphigoid diseases. The prognosis is usually good. For decisions about (local or systemic) immunosuppressive therapy, gerontological aspects should be taken into consideration.


Subject(s)
Dermatology/standards , Geriatric Assessment/methods , Immunologic Factors/therapeutic use , Immunosuppressive Agents/therapeutic use , Pemphigoid, Bullous/diagnosis , Pemphigoid, Bullous/therapy , Aged , Aged, 80 and over , Female , Geriatrics/standards , Germany , Humans , Immunologic Factors/standards , Immunosuppressive Agents/standards , Male , Practice Guidelines as Topic
10.
Dis Esophagus ; 25(5): 465-9, 2012 Jul.
Article in English | MEDLINE | ID: mdl-21951298

ABSTRACT

The closure of a large hiatal hernia still represents a challenge for the surgeon. Mesh reinforcement of a hiatoplasty generally decreases recurrence rate. An artificial mesh is cheaper compared with a biologic one, but has a higher complication rate. Our aim was to introduce a new biologic reinforcement method with less expenses. During organ donation for transplantation, tissue islets from pericardium and fascia lata were cryopreserved in a tissue bank. Later, the grafts were transplanted on the diaphragm of mongrel dogs. After 1, 3, and 6 months, the animals were sacrificed, and the transplanted patches were macroscopically and microscopically examined. There were no macroscopic signs of inflammation, abcedation, or significant adhesion formation. The grafts were well recognizable, with palpable thickening and moderate shrinkage. Microscopically, an organization process with fibrosis, neovascularization, and peritoneal integration could be observed. Reinforcement of a hiatoplasty with connective tissue transfer either with cryopreserved or autologous tissue is a good option. This is a cheap and easy method, which should also be tested in human interventions.


Subject(s)
Bioprosthesis , Diaphragm/surgery , Hernia, Hiatal/surgery , Herniorrhaphy/methods , Tissue Transplantation/methods , Animals , Connective Tissue/transplantation , Dogs , Fascia Lata/transplantation , Humans , Pericardium/transplantation , Secondary Prevention , Surgical Mesh
11.
Transplant Proc ; 43(10): 3694-6, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22172828

ABSTRACT

The prediction of graft rejection can play an important part in graft survival. Analysis of immune reactions has shown that graft rejection shares mechanisms with recurrent abortions during pregnancy. Progesterone-induced blocking factor (PIBF), a mediator of progesterone that blocks natural killer cell activity in peripheral blood, produces antiabortive effects. The aim of this study was to examine the PIBF concentration in the urine of transplanted recipients. The study included 116 white adults (70 men and 46 women) of median age 49.3 years, who had undergone kidney transplantations. The median duration after transplantation was 3.46 years. The average period between renal disease and our measurement was 12.3 years, and the median interval between graft rejection and our study was 1.75 years. Urine samples were used to measure PIBF concentrations by an enzyme-linked immunsorbent assay. PIBF urinary concentrations decreased significantly in patients who experienced ≥1 rejection episode (31.8±2.2 ng/mL) compared with those without any episode (22.7±1.2 ng/ml; P<.01). Moreover, the urinary PIBF level was significantly lower among patients who had increased creatinine and urea nitrogen levels in blood samples (P<.05 and P<.01, respectively). Decreased PIBF values in kidney transplant patients followed previous rejection episodes. A close negative correlation was observed between urinary PIBF concentrations and blood levels of creatinine and urea nitrogen. These findings suggested that PIBF detection may predict graft rejection in transplant recipients.


Subject(s)
Graft Rejection/etiology , Kidney Transplantation/adverse effects , Pregnancy Proteins/urine , Suppressor Factors, Immunologic/urine , Biomarkers/blood , Biomarkers/urine , Blood Urea Nitrogen , Creatinine/blood , Enzyme-Linked Immunosorbent Assay , Female , Graft Rejection/urine , Humans , Hungary , Male , Middle Aged , Predictive Value of Tests , ROC Curve , Time Factors , Treatment Outcome
12.
Surg Infect (Larchmt) ; 12(6): 483-9, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22142314

ABSTRACT

BACKGROUND: Surgical site infections (SSI) are the third most common hospital-acquired infections and account for 14% to 16% of all such infections. In elective colorectal operations, the international SSI rate ranges from 4.7%-25%. In a previous retrospective study in this department, the SSI rate was unacceptably high (25%), and the promising different international evaluations of triclosan-coated suture materials encouraged us to create a multicenter randomized trial to improve our results. The main goal of this study was to compare triclosan-coated and uncoated absorbable suture (PDS Plus(®) with PDS II(®)) in elective colorectal operations. METHODS: This was an internet-based study involving seven surgical centers. All the elective colorectal operations were performed by experienced surgeons. For abdominal fascia closure, running looped PDS was applied; triclosan-coated or uncoated PDS was chosen by computer randomization. Pre-operative and peri-operative variables such as gender, body mass index, neoadjuvant therapy, type II diabetes mellitus, amount of wound dressing material used, nursing days, and microbiological results were recorded. After the operation, the patient's data and risk factors were collected in a password-protected online database. RESULTS: From 485 patients randomized, SSI was documented in 47 patients (12.5%), 23 (12.2%) in the group having triclosan-coated sutures (n=188) and 24 (12.2%) in the uncoated suture group (n=197), a non-significant difference. Of all SSIs, 13 (27.7%) were diagnosed only after discharge, being recognized in the outpatient setting, with four patients in the triclosan suture group (8.5%) and nine in the uncoated suture group (19.2%) being affected with no significant differences in the demographic data. Microbiological examinations, in addition to the same colon flora in both groups, revealed two gram-positive infections in the uncoated suture group. The hospital stay and costs of dressings were significantly higher in patients having SSIs. CONCLUSION: Compared with the previous retrospective studies of this department, the implementation of looped PDS decreased the incidence of SSI by one-half, whether the suture was triclosan-coated or not. It seems that patient factors are less important than operative factors in the occurrence of SSI, and there were no differences between elective colon and rectal operations in the development of incisional infections. No beneficial effect of triclosan against gram-positive bacteria, which has been reported in the literature, could be confirmed in our study. We could not show an effect against gram-negative enteric microorganisms. Higher additional costs and longer hospital stay with SSI were confirmed.


Subject(s)
Anti-Infective Agents, Local/administration & dosage , Colonic Diseases/surgery , Rectal Diseases/surgery , Surgical Wound Infection/prevention & control , Sutures , Triclosan/administration & dosage , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prospective Studies , Wound Healing/drug effects , Young Adult
13.
Anticancer Res ; 31(5): 1769-75, 2011 May.
Article in English | MEDLINE | ID: mdl-21617238

ABSTRACT

BACKGROUND: Possible predictive markers of response to neoadjuvant radiochemotherapy (NRCT) of esophageal cancer have been identified. PATIENTS AND METHODS: Patient biopsies were obtained from both tumor and normal tissue before the NRCT of locally advanced esophageal squamous cell carcinoma. Protein solutions were separated and immunoblot analysis was performed with heat shock protein (Hsp)16.2, heme-binding protein 2 (SOUL), BCL2-associated X protein (Bax), B-cell-associated leukemia protein 2 (Bcl-2) and heat shock protein 90 (Hsp90) antibodies. Following NRCT, the patients were restaged according to the Response Evaluation Criteria In Solid Tumors (RECIST). Following resections the pathological down-staging was evaluated. RESULTS: Clinical restaging revealed a response rate of 65%. Pathological examination revealed down-staging in 30% and 25% of the cases for the T and N categories respectively. Compared to the normal esophageal mucosa, a decreased expression of Hsp16.2, Hsp90 and SOUL proteins and an increased Bax/Bcl-2 ratio was found in the responding tumors. CONCLUSION: Hsp16,2, Hsp90 and SOUL expression and Bax/ Bcl-2 ratio correlates to the efficacy of NRCT and predict outcome in patients with locally advanced squamous-cell esophageal cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/therapy , Esophageal Neoplasms/therapy , Neoadjuvant Therapy , Neoplasm Proteins/metabolism , Adult , Aged , Blotting, Western , Carcinoma, Squamous Cell/metabolism , Case-Control Studies , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Combined Modality Therapy , Esophageal Neoplasms/metabolism , Esophagus/drug effects , Esophagus/metabolism , Esophagus/radiation effects , Female , Fluorouracil/administration & dosage , HSP90 Heat-Shock Proteins/metabolism , Heat-Shock Proteins, Small/metabolism , Heme-Binding Proteins , Hemeproteins/metabolism , Humans , Intracellular Signaling Peptides and Proteins , Male , Middle Aged , Neoplasm Staging , Pregnancy Proteins/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Radiotherapy, Adjuvant , Survival Rate , Treatment Outcome , bcl-2-Associated X Protein/metabolism
14.
Transplant Proc ; 42(6): 2333-5, 2010.
Article in English | MEDLINE | ID: mdl-20692474

ABSTRACT

There is increasing evidence that nonmelanoma skin cancers (NMSCs) are the most frequently observed tumors in transplant recipients. The incidence of posttransplantation NMSC was determined using our dermatologic screening program. Included in the study were 116 white adults (70 men and 46 women; median age, 49.3 years) who had undergone kidney or combined kidney-pancreas transplantation, with follow-up from September 2008 to December 2009. All patients underwent a full skin examination for NMSC, and completed a standardized questionnaire. Screening resulted in detection of 16 NMSCs in 11 patients out of 116 (9.5%). Lesions were equally distributed by sex, and were detected at a median of 4.1 years posttransplantation. Histologic analysis verified 13 basal cell carcinomas and 3 squamous cell carcinomas (ratio, 4:1). The incidence of NMSC was significantly greater in patients who received cyclosporine immunosuppression therapy (16 vs 1; P < .05), had experienced 2 or more painful sunburns before transplantation (10 vs 11), or worked outdoors (10 vs 11). These data indicate the relevance of skin cancer surveillance in transplant recipients. Our results correspond to international statistics except for the ratio of basal cell carcinoma to squamous cell carcinoma. Further studies are needed to elucidate the reasons for this difference.


Subject(s)
Organ Transplantation/adverse effects , Skin Neoplasms/epidemiology , Carcinoma, Basal Cell/epidemiology , Carcinoma, Squamous Cell/epidemiology , Female , Follow-Up Studies , Humans , Hungary/epidemiology , Kidney Transplantation/adverse effects , Male , Middle Aged , Pancreas Transplantation/adverse effects , Skin/pathology , Skin Neoplasms/classification , Surveys and Questionnaires , Time Factors
15.
Transplant Proc ; 42(6): 2336-8, 2010.
Article in English | MEDLINE | ID: mdl-20692475

ABSTRACT

Transplant recipients are at high risk of nonmelanoma skin cancer (NMSC). Ultraviolet radiation can generate oxygen free radicals (OFRs), leading to oxidative stress and carcinogenesis, primarily during immunosuppression therapy. In the present study, changes in oxidative stress were examined in transplant recipients with and without NMSC. The study included 116 white adults who had undergone kidney or combined kidney-pancreas transplantation. Dermatologic follow-up revealed 16 NMSCs (13.8%). To monitor oxidative stress, peripheral blood samples were used to measure malondialdehyde (MDA), reduced glutathione, sulfhydryl (-SH) groups, OFRs, and activity of myeloperoxidase, superoxide dismutase, and catalase. The mean (SD) plasma MDA concentration was significantly greater in patients without NMSC compared with healthy control individuals (0.48+/-0.05 nmol/mL; P < .05), whereas MDA concentration in hemolysate was slightly increased. In peripheral blood samples, the MDA concentration in both plasma (0.71+/-0.03 nmol/mL) and hemolysate (87.74+/-1.25 nmol/mL) was significantly increased in the NMSC group compared with the healthy control group (0.24+/-0.05 nmol/mL vs 75.87+/-2.8 nmol/mL; P < .05) or patients without NMSC (0.48+/-0.04 nmol/mL vs 79.62+/-2.77 nmol/mL; P < .05). The reduced glutathione concentration was significantly decreased in the -SH groups compared with the healthy control group (P < .05). Antioxidant activity of myeloperoxidase (0.78+/-0.05 IU/mL) and catalase (1855.8+/-45.41 IU/mL) was significantly increased in the group without NMSC compared with the healthy control group (0.41+/-0.1 IU/mL vs 1642.07+/-82.96 IU/mL) and the NMSC group (0.93+/-0.03 IU/mL vs 2180.5+/-15.03 IU/mL). The superoxide dismutase activity was decreased slightly but not significantly. Total production of OFRs was significantly greater in the NMSC group compared with the non-NMSC group or the healthy control group (P < .05). These findings suggest that an imbalance exists between pro-oxidant and antioxidant status in transplant recipients, with a significant difference in patients with vs without NMSC.


Subject(s)
Kidney Transplantation/adverse effects , Organ Transplantation/adverse effects , Oxidative Stress , Pancreas Transplantation/adverse effects , Skin Neoplasms/epidemiology , Catalase/blood , Female , Free Radicals/blood , Glutathione/blood , Humans , Male , Malondialdehyde/blood , Middle Aged , Skin Neoplasms/blood , Skin Neoplasms/physiopathology , Sulfhydryl Compounds/blood , Superoxide Dismutase/blood
16.
Transplant Proc ; 41(1): 60-2, 2009.
Article in English | MEDLINE | ID: mdl-19249476

ABSTRACT

Cold preservation prior to small bowel transplantation can moderate tissue oxidative injury. This stress triggers several intracellular pathways via mitogen activated protein (MAP) kinases. MAP kinases include the extracellular signal related kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAP kinase. Pituitary adenylate cyclase-activating polypeptide (PACAP) plays a central role in intestinal physiology. We sought to investigate the effect of PACAP on the activation of MAP kinases during cold preservation of the small bowel. Total orthotopic intestinal autotransplantation was performed on 40 Wistar rats. Perfused grafts were stored in University of Wisconsin (UW) solution for 1 (GI), 2 (GII), 3 (GIII), or 6 hours (GIV) without or with 30 PACAP, namely 1 (GV), 2 (GVI), 3 (GVII), or 6 hours (GVIII). After 3 hours of reperfusion in all groups, the activation of MAP kinases were measured using immunocytochemistry of small bowel tissue. Among the UW preserved grafts (GI-GIV), phosphorylated ERK1/2 level were decreased, while phosphorylated JNK1/2 and p38 MAP kinase activation were elevated compared with control levels. In GV-GVIII PACAP we observed enhanced phospho-ERK1/2 appearance with decreased JNK and p38 MAP kinase activity at the end of the reperfusion periods. We concluded that cold preservation decreased phosphorylated ERK1/2 levels and increased JNK1/2 and p38 MAP kinase activities, which meant that cold storage triggered apoptotic cell death. In contrast, PACAP treatment induced signalling pathways protective against oxidative injury by MAP kinases in bowel tissue.


Subject(s)
Extracellular Signal-Regulated MAP Kinases/metabolism , Intestine, Small/enzymology , Intestine, Small/transplantation , JNK Mitogen-Activated Protein Kinases/metabolism , Organ Preservation/methods , Pituitary Adenylate Cyclase-Activating Polypeptide/pharmacology , Adenosine , Allopurinol , Animals , Enzyme Activation/drug effects , Extracellular Signal-Regulated MAP Kinases/drug effects , Glutathione , Graft Survival , Insulin , JNK Mitogen-Activated Protein Kinases/drug effects , Male , Organ Preservation Solutions , Raffinose , Rats , Rats, Wistar , Transplantation, Autologous
17.
Transplant Proc ; 41(1): 57-9, 2009.
Article in English | MEDLINE | ID: mdl-19249475

ABSTRACT

Tissue injury caused by cold preservation and reperfusion during small bowel transplantation remains an unsolved problem. Increasing evidence suggests that pituitary adenylate cyclase-activating polypeptide (PACAP) has protective effects in several ischemia-reperfusion (I/R) models. This study investigated the effect of PACAP-38 on oxidative stress in autotransplanted intestine. We established sham-operated, I/R, and autotransplanted groups in Wistar rats (n = 55). We applied ischemia for 1 (GI), 2 (GII), or 3 hours (GIII). In autotransplanted groups, we performed total orthotopic intestinal autotransplantation. Grafts were preserved in University of Wisconsin (UW) solution for 1 (GIV), 2 (GV), 3 (GVI), or 6 (GVII) hours and in PACAP-38-containing UW for 1 (GVIII), 2 (GIX), 3 (GX), or 6 (GXI) hours. Reperfusion lasted 3 hours in each group. Endogenous PACAP-38 values were measured by radioimmunoassay. Oxidative stress parameters malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) were measured in tissue homogenates. Concentration of endogenous PACAP-38 significantly decreased in GI to GIII compared with the sham-operated animals following I/R periods (P < .05). Cold preservation in UW and reperfusion of the intestine increased the level of tissue MDA in GIV to GVII, which correlated with the duration of cold storage. The content of GSH decreased in GIV to GVII to levels that were significantly different between GIV and GVIII and between GVII and GXI. SOD activity decreased dramatically in GIV to GVII with significantly higher activity in GIX to GXI. Our findings confirmed that I/R decreased endogenous PACAP-38 concentration. Administration of PACAP-38 to UW solution mitigated the oxidative injury during intestinal autotransplantation.


Subject(s)
Intestines/blood supply , Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism , Reperfusion Injury/physiopathology , Adenosine , Allopurinol , Animals , Cold Temperature , Glutathione/metabolism , Insulin , Male , Malondialdehyde/metabolism , Organ Preservation/methods , Organ Preservation Solutions , Raffinose , Rats , Rats, Wistar , Superoxide Dismutase/metabolism
19.
Surg Endosc ; 22(3): 679-82, 2008 Mar.
Article in English | MEDLINE | ID: mdl-17623243

ABSTRACT

BACKGROUND: This study aimed to determine the possible cause for an unacceptable frequency of postresectional pneumothorax in cases of ultrasonic scalpel use without a further reinforcing maneuver in lung biopsy during video-assisted thoracic surgery (VATS). METHODS: Data for a series of 16 consecutive VATS lung biopsy patients (group A) in which a disturbingly high number of minor and medium complications occurred were compared with data for a group of 20 patients previously subject to the same ultrasonic lung biopsy method (group B) without complication. RESULTS: The two groups were identical in terms of all significant factors considered in relation to ultrasonic scalpel biopsy. Six notable air leakage complications occurred among the 16 patients of group A. One patient needed redrainage while still in the hospital. Two other patients required readmission and redrainage. In 4 of the 16 cases, late pneumothorax was detected after a "silent" 48-h postoperative period prolonging their hospital stay. Altogether, three medium complications occurred in group A, as compared with none in group B. The drainage duration in group B was not significantly shorter than in group A . Multivariate analysis showed a significant difference in complications favoring group B (odds ratio, 1.88). CONCLUSIONS: A high postoperative air leakage rate was observed in a simple case series using an unsecured harmonic scalpel after a randomized trial of the same method in the same institute with a diametrically opposite outcome. The medium complication rate of 3 in 16 cases is unacceptable for a minor procedure such as lung biopsy. The two groups differed only in their thromboembolic prophylaxis protocol. Therefore, it is hypothesized that the recent introduction of low-molecular-weight heparin from day 1 may influence the complication rate. The authors' observation calls for caution in use of the harmonic scalpel on lung tissue without reinforcing maneuvers (i.e., stitches or clips). To avoid unnecessary complications, operative technique adjustment is recommended.


Subject(s)
Biopsy, Needle/adverse effects , Hemothorax/etiology , Lung Diseases/diagnosis , Pneumothorax/etiology , Thoracic Surgery, Video-Assisted/methods , Adult , Age Distribution , Biopsy, Needle/methods , Cohort Studies , Confidence Intervals , Evidence-Based Medicine , Female , Follow-Up Studies , Hemothorax/epidemiology , Humans , Incidence , Lung Diseases/surgery , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Pneumothorax/epidemiology , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Probability , Retrospective Studies , Risk Assessment , Sex Distribution , Surgical Instruments/adverse effects , Thoracic Surgery, Video-Assisted/adverse effects , Ultrasonics/adverse effects
20.
Surg Endosc ; 22(4): 881-4, 2008 Apr.
Article in English | MEDLINE | ID: mdl-17973164

ABSTRACT

BACKGROUND: Although laparoscopic repair of large, mostly paraesophageal hiatal hernias is widely applied, there is a great concern regarding the higher recurrence rate associated with this procedure. In order to reduce this high recurrence rate, several techniques have been developed, mostly applying a mesh prosthesis for hiatal reinforcement. METHODS: We have recently introduced a new laparoscopic technique in which the hiatal closure is reinforced with the teres ligament. To date 26 patients have been entered into this ongoing prospective study. After the operation patients were called back on a regular basis for symptom evaluation and barium swallow. All 26 patients agreed to undergo barium swallow, with a mean follow-up of 35 months. RESULTS: The mean operative time was 115 min. Perioperative morbidity was 11.5%, and conversion to an open procedure was performed in six cases. No mortality was registered. Anatomic recurrence, investigated by barium swallows was observed in four patients (15.3%). Of those four, only one (3.85%) had a symptomatic recurrent paraesophageal hernia; the other three had asymptomtic sliding hernias. In three of the four patients with anatomic recurrence, the diameter of the hiatal hernia was greater than 9 cm at the original operation, and the fourth patient underwent reoperation for recurrent hiatal hernia. No symptomatic recurrence was found in patients with diameter of hiatal hernia between 6 and 9 cm. CONCLUSIONS: Laparoscopic reinforcement of the hiatal closure with the ligamentum teres is safe and effective treatment for large hiatal hernias. However, it appears that patients with extremely large hiatal hernias are at greater risk of recurrence, and therefore large hernias are not suitable for this new technique.


Subject(s)
Hernia, Hiatal/surgery , Laparoscopy/methods , Ligaments/transplantation , Adult , Aged , Barium Sulfate , Contrast Media , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Recurrence , Treatment Outcome
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