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1.
mBio ; 14(4): e0108323, 2023 08 31.
Article in English | MEDLINE | ID: mdl-37382440

ABSTRACT

Infection by retroviruses as HIV-1 requires the stable integration of their genome into the host cells. This process needs the formation of integrase (IN)-viral DNA complexes, called intasomes, and their interaction with the target DNA wrapped around nucleosomes within cell chromatin. To provide new tools to analyze this association and select drugs, we applied the AlphaLISA technology to the complex formed between the prototype foamy virus (PFV) intasome and nucleosome reconstituted on 601 Widom sequence. This system allowed us to monitor the association between both partners and select small molecules that could modulate the intasome/nucleosome association. Using this approach, drugs acting either on the DNA topology within the nucleosome or on the IN/histone tail interactions have been selected. Within these compounds, doxorubicin and histone binders calixarenes were characterized using biochemical, in silico molecular simulations and cellular approaches. These drugs were shown to inhibit both PFV and HIV-1 integration in vitro. Treatment of HIV-1-infected PBMCs with the selected molecules induces a decrease in viral infectivity and blocks the integration process. Thus, in addition to providing new information about intasome-nucleosome interaction determinants, our work also paves the way for further unedited antiviral strategies that target the final step of intasome/chromatin anchoring. IMPORTANCE In this work, we report the first monitoring of retroviral intasome/nucleosome interaction by AlphaLISA. This is the first description of the AlphaLISA application for large nucleoprotein complexes (>200 kDa) proving that this technology is suitable for molecular characterization and bimolecular inhibitor screening assays using such large complexes. Using this system, we have identified new drugs disrupting or preventing the intasome/nucleosome complex and inhibiting HIV-1 integration both in vitro and in infected cells. This first monitoring of the retroviral/intasome complex should allow the development of multiple applications including the analyses of the influence of cellular partners, the study of additional retroviral intasomes, and the determination of specific interfaces. Our work also provides the technical bases for the screening of larger libraries of drugs targeting specifically these functional nucleoprotein complexes, or additional nucleosome-partner complexes, as well as for their characterization.


Subject(s)
Nucleosomes , Spumavirus , Humans , Histones/genetics , Virus Integration , Chromatin , Retroviridae/genetics , Integrases/genetics , DNA, Viral/chemistry , Spumavirus/genetics
2.
Biochim Biophys Acta Rev Cancer ; 1876(2): 188597, 2021 12.
Article in English | MEDLINE | ID: mdl-34332021

ABSTRACT

Homologous recombination (HR) is involved in repairing DNA double-strand breaks (DSB), the most harmful for the cell. Regulating HR is essential for maintaining genomic stability. In many forms of cancer, overactivation of HR increases tumor resistance to DNA-damaging treatments. RAD51, HR's core protein, is very often over-expressed in these cancers and plays a critical role in cancer cell development and survival. Targeting RAD51 directly to reduce its activity and its expression is therefore one strategy to sensitize and overcome resistance cancer cells to existing DNA-damaging therapies which remains the limiting factor for the success of targeted therapy. This review describes the structure and biological roles of RAD51, summarizes the different targeted sites of RAD51 and its inhibitory compounds discovered and described in the last decade.


Subject(s)
Homologous Recombination/genetics , Rad51 Recombinase/metabolism , Humans
3.
J Intern Med ; 287(5): 569-579, 2020 05.
Article in English | MEDLINE | ID: mdl-32037598

ABSTRACT

BACKGROUND: Dysfunctional mitochondria have an influence on inflammation and increased oxidative stress due to an excessive production of reactive oxygen species. The mitochondrial DNA copy number (mtDNA-CN) is a potential biomarker for mitochondrial dysfunction and has been associated with various diseases. However, results were partially contrasting which might have been caused by methodological difficulties to quantify mtDNA-CN. OBJECTIVE: We aimed to investigate whether mtDNA-CN is associated with peripheral arterial disease (PAD) as well as all-cause mortality and cardiovascular events during seven years of follow-up. METHODS: A total of 236 male patients with PAD from the Cardiovascular Disease in Intermittent Claudication (CAVASIC) study were compared with 249 age- and diabetes-matched controls. MtDNA-CN was measured with a well-standardized plasmid-normalized quantitative PCR-based assay determining the ratio between mtDNA-CN and nuclear DNA. RESULTS: Individuals in the lowest quartile of mtDNA-CN had a twofold increased risk for PAD which, however, was no longer significant after adjusting for leukocytes and platelets. About 67 of the 236 patients had already experienced a cardiovascular event at baseline and those in the lowest mtDNA-CN quartile had a 2.34-fold increased risk for these events (95% CI 1.08-5.13). During follow-up, 37 PAD patients died and 66 patients experienced a cardiovascular event. Patients in the lowest mtDNA-CN quartile had hazard ratios of 2.66 (95% CI 1.27-5.58) for all-cause-mortality and 1.82 (95% CI 1.02-3.27) for cardiovascular events compared with the combined quartile 2-4 (adjusted for age, smoking, CRP, diabetes, prevalent cardiovascular disease, leukocytes and platelets). CONCLUSION: This investigation supports the hypothesis of mitochondrial dysfunction in peripheral arterial disease and shows an association of low mtDNA-CNs with all-cause-mortality and prevalent and incident cardiovascular disease in PAD patients with intermittent claudication.


Subject(s)
Cardiovascular Diseases/genetics , DNA Copy Number Variations , DNA, Mitochondrial/genetics , Peripheral Arterial Disease/genetics , Cardiovascular Diseases/complications , Cardiovascular Diseases/mortality , Case-Control Studies , DNA Copy Number Variations/genetics , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Mitochondrial Diseases/complications , Mitochondrial Diseases/genetics , Mortality , Peripheral Arterial Disease/complications , Peripheral Arterial Disease/mortality , Proportional Hazards Models , Real-Time Polymerase Chain Reaction , Risk Factors
4.
Z Rheumatol ; 73(7): 615-22, 2014 Sep.
Article in German | MEDLINE | ID: mdl-24972749

ABSTRACT

BACKGROUND: Capillaroscopy is an established tool to assess morphological and functional findings of the microcirculation which have a confirmed association with disease activity and damage of inflammatory rheumatic diseases, especially systemic sclerosis. Hairpin-shaped capillaries with normal density predict a very low risk for collagenosis. METHODS: Own databases were evaluated with respect to the topic of the manuscript and the current literature was evaluated. RESULTS: The healthy population does not only demonstrate hairpin shape as capillaroscopic normal findings and morphological and functional abnormalities can also be found which show various patterns depending on gender and age. These can be found in healthy persons and also patients with collagenosis. Ectasia and sludge phenomenon are more common in women and tortuous capillaries are more common in men. Capillary filling is often decreased in women and increased in male patients. CONCLUSION: When assessing capillaroscopy findings, gender and the morphological or functional alterations which can be found in the normal healthy population should be taken into consideration. In further studies with capillaroscopy as the target parameter, the potential source of the disturbance should be known, especially in small populations, and if necessary balanced by weighted randomization.


Subject(s)
Inflammation/pathology , Microscopic Angioscopy/statistics & numerical data , Microvessels/pathology , Rheumatic Diseases/pathology , Vasculitis/pathology , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Sex , Sex Characteristics
5.
Zentralbl Chir ; 137(5): 460-5, 2012 Oct.
Article in German | MEDLINE | ID: mdl-23136105

ABSTRACT

BACKGROUND: Thrombangiitis obliterans or Buerger's disease is a segmental inflammatory disease affecting small and medium-sized veins and arteries, which most often affects young smokers leading to thrombophlebitis and acral ischaemic syndromes, inducing high amputation rates. Based on positive results of a former pilot study we report on our results of immunoadsorption (IA) in clinical routine care, where IA was offered as a treatment option. PATIENTS AND METHODS: The uncontrolled course of 12 consecutive TAO-patients treated by IA on a series of 5 consecutive days was observed. Follow-up period was 14.1 (ranging from 1-26) months. RESULTS: Eight patients were treated with one, four patients completed 2 IA-series. In 9 patients an early onset and lasting clinical improvement and an improvement of ischaemia was noted. The intake of pain-relievers (especially opioids) sank drastically. Eight patients returned to work. Retrospectively, in two out of three treatment failures the correct diagnosis of TAO was questionable. CONCLUSION: IA seems to be a promising treatment option for patients suffering from TAO which should be further evaluated in controlled clinical trials.


Subject(s)
Immunosorbent Techniques , Thromboangiitis Obliterans/therapy , Adult , Cohort Studies , Female , Fingers/blood supply , Follow-Up Studies , Foot/blood supply , Humans , Ischemia/etiology , Ischemia/therapy , Male , Middle Aged , Raynaud Disease/therapy , Toes/blood supply
7.
Vasa ; 40(2): 123-30, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21500177

ABSTRACT

BACKGROUND: We surveyed the quality of risk stratification politics and monitored the rate of entries to our company-wide protocol for venous thrombembolism (VTE) prophylaxis in order to identify safety concerns. PATIENTS AND METHODS: Audit in 464 medical and surgical patients to evaluate quality of VTE prophylaxis. RESULTS: Patients were classified as low 146 (31 %), medium 101 (22 %), and high risk cases 217 (47 %). Of these 262 (56.5 %) were treated according to their risk status and in accordance with our protocol, while 9 more patients were treated according to their risk status but off-protocol. Overtreatment was identified in 73 (15.7 %), undertreatment in 120 (25,9 %) of all patients. The rate of incorrect prophylaxis was significantly different between the risk categories, with more patients of the high-risk group receiving inadequate medical prophylaxis (data not shown; p = 0.038). Renal function was analyzed in 392 (84.5 %) patients. In those patients with known renal function 26 (6.6 %) received improper medical prophylaxis. If cases were added in whom prophylaxis was started without previous creatinine control, renal function was not correctly taken into account in 49 (10.6 %) of all patients. Moreover, deterioration of renal function was not excluded within one week in 78 patients (16.8 %) and blood count was not re-checked in 45 (9.7 %) of all patients after one week. There were more overtreatments in surgical (n = 53/278) and more undertreatments in medical patients (n = 54/186) (p = 0.04). Surgeons neglected renal function and blood controls significantly more often than medical doctors (p-values for both < 0.05). CONCLUSIONS: We found a low adherence with our protocol and substantial over- and undertreatment in VTE prophylaxis. Besides, we identified disregarding of renal function and safety laboratory examinations as additional safety concerns. To identify safety problems associated with medical VTE prophylaxis and "hot spots" quality management-audits proved to be valuable instruments.


Subject(s)
Anticoagulants/therapeutic use , Practice Patterns, Physicians' , Quality Indicators, Health Care , Venous Thromboembolism/prevention & control , Aged , Aged, 80 and over , Chi-Square Distribution , Cross-Sectional Studies , Germany , Guideline Adherence , Health Care Surveys , Humans , Middle Aged , Practice Guidelines as Topic , Practice Patterns, Physicians'/statistics & numerical data , Quality Indicators, Health Care/statistics & numerical data , Risk Assessment , Risk Factors , Venous Thromboembolism/etiology
8.
Vasa ; 40(1): 6-19, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21283969

ABSTRACT

Due to its high association with Raynaud's phenomenon systemic sclerosis (SSc) is probably the most common connective tissue disease seen by vascular specialists. In part 1 of our systematic overview we summarize classification concepts of scleroderma disorders, the epidemiologic and genetic burden, the complex pathophysiologic background, and the clinical features and the stage-dependent capillary microscopic features of SSc. Furthermore, we address the diagnostic recommendations propagated by the German Network for Systemic Sclerosis and the Task Force for Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology, the European Respiratory Society, and the International Society of Heart and Lung Transplantation.


Subject(s)
Hypertension, Pulmonary/etiology , Raynaud Disease/etiology , Scleroderma, Systemic/classification , Ulcer/etiology , Capillaries/pathology , Capillaries/physiopathology , Europe , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/epidemiology , Hypertension, Pulmonary/physiopathology , Practice Guidelines as Topic , Predictive Value of Tests , Raynaud Disease/diagnosis , Raynaud Disease/epidemiology , Raynaud Disease/physiopathology , Risk Factors , Scleroderma, Systemic/complications , Scleroderma, Systemic/diagnosis , Scleroderma, Systemic/epidemiology , Scleroderma, Systemic/physiopathology , Severity of Illness Index , Societies, Medical , Terminology as Topic , Ulcer/diagnosis , Ulcer/epidemiology , Ulcer/physiopathology
9.
Vasa ; 40(1): 20-30, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21283970

ABSTRACT

Here we give an overview over treatment recommendations propagated by the European League Against Rheumatism (EULAR), EULAR Scleroderma Trials and Research Group, the German Network for Systemic Sclerosis, the European Respiratory Society, and the International Society of Heart and Lung Transplantation. As response to immunosuppressant (IS) therapy is usually weaker in systematic sclerosis (SSc) compared to other connective tissue disorders IS should be considered with caution. To prevent scleroderma renal crisis steroid doses should not exceed 15 mg/d. The definitive role of a number of new immunosuppressant drugs and the effects of autologous stem cell transplantation in systemic clerosis (SSc) have to be elucidated. Prostanoids, especially iloprost, are widely used as intravenous formulas for the treatment of severe Raynaud's phenomenon (RP) and digital ulcers (DU). Calcium antagonists are of limited therapeutic value. Bosentan, an oral endothelin receptor antagonists (ETRA), was shown to prevent new DU, but failed to heal existing DU, while the oral phopshodiesterase inhibitor (PDI) Sildenafil reduces the occurrence of RP and might be effective in ulcer healing. Combination therapies of PDI with ETRA are currently evaluated. Therapy of pulmonary arterial hypertension (PAH) is usually started as oral monotherapy, frequently using an ETRA. When this first-line therapy is not tolerated ETRA is substituted by PDI. If treatment goals are not reached with monotherapy combinationtherapy is started, for example by adding a PDI to an existing ETRA. In general, treatment of PAH in patients with connective tissue disease follows the same algorithms as in idiopathic PAH.


Subject(s)
Cardiovascular Agents/therapeutic use , Immunosuppressive Agents/therapeutic use , Raynaud Disease/drug therapy , Scleroderma, Systemic/drug therapy , Antihypertensive Agents/therapeutic use , Drug Therapy, Combination , Europe , Familial Primary Pulmonary Hypertension , Humans , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/immunology , Hypertension, Pulmonary/physiopathology , Practice Guidelines as Topic , Raynaud Disease/immunology , Raynaud Disease/physiopathology , Scleroderma, Systemic/immunology , Scleroderma, Systemic/physiopathology , Societies, Medical , Stem Cell Transplantation , Treatment Outcome , Ulcer/drug therapy , Ulcer/immunology , Ulcer/physiopathology
10.
Zentralbl Chir ; 135(4): 359-62, 2010 Aug.
Article in German | MEDLINE | ID: mdl-20806142

ABSTRACT

Spinal cord stimulation (SCS) has been successfully used to treat chronic pain syndromes for decades. For this purpose, an electrode is implanted into the epidural space under local anaesthesia and connected to a neurostimulator which applies a weak direct current to the dorsal roots of the spinal column. Besides pain control, SCS increases the blood supply in the stimulated area. This effect is mediated by a sympathicolytic effect and the liberation of vasodilatators within the stimulated skin area. A Cochrane meta-analysis has revealed a significantly increased limb salvage rate in patients with non-reconstructable critical limb ischaemia (CLI) treated with SCS. The effect of SCS in CLI might be predicted by the measurement of forefoot transcutaneous pO (2) in supine and dependent positions, which renders trial stimulation unnecessary in many cases.


Subject(s)
Arterial Occlusive Diseases/physiopathology , Arterial Occlusive Diseases/therapy , Electrodes, Implanted , Evidence-Based Medicine , Implantable Neurostimulators , Ischemia/therapy , Leg/blood supply , Spinal Cord/physiopathology , Spinal Nerve Roots/physiopathology , Animals , Epidural Space , Foot/blood supply , Humans , Ischemia/physiopathology , Oxygen/blood , Prognosis , Sympathetic Nervous System/physiopathology , Vasodilation/physiology
11.
Lupus ; 19(9): 1087-95, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20693202

ABSTRACT

Skin discolorations and skin lesions due to vascular pathologies are common clinical features in systemic lupus erythematosus. A variety of clinical manifestations such as Raynaud's phenomenon, acrocyanosis, livedo patterns, erythematous or violaceous macules and papules or necrosis are triggered by heterogeneous pathophysiological mechanisms such as vasospasm, vasculitis or thromboembolism. A standardized macro- and microvascular assessment is necessary to establish the correct diagnosis. We describe and illustrate common clinical features of vascular skin manifestations in systemic lupus erythematosus and present a diagnostic algorithm.


Subject(s)
Lupus Erythematosus, Systemic/diagnosis , Raynaud Disease/diagnosis , Skin Diseases, Vascular/diagnosis , Algorithms , Humans , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/physiopathology , Raynaud Disease/etiology , Raynaud Disease/pathology , Skin/pathology , Skin Diseases, Vascular/etiology , Skin Diseases, Vascular/pathology , Thromboembolism/diagnosis , Thromboembolism/etiology , Vasculitis/diagnosis , Vasculitis/etiology
12.
Vasa ; 39(2): 145-52, 2010 May.
Article in English | MEDLINE | ID: mdl-20464670

ABSTRACT

BACKGROUND: We compared medical secondary prevention in patients with peripheral arterial disease stage II (Fontaine) located in the femoro-popliteal artery managed by vascular surgeons and medical doctors / angiologists in our multidisciplinary vascular center. PATIENTS AND METHODS: We retrospectively analyzed demission protocols of in-hospital treatments between 01.01.2007 and 20.06.2008. RESULTS: We surveyed 264 patients (54.2 % women; mean age 67.52 +/- 8.98 yrs), 179 (67.8 %) primarily treated by medical doctors / angiologists and 85 (32.2 %) primarily managed by vascular surgeons. Medical doctors / angiologists treated more women (n = 109) than men (n = 34), (p = 0.002) and documented smoking and diabetes mellitus more often (p < 0.001) than vascular surgeons. Besides, patients had similar cardiovascular risk profiles and concomitant diseases, vascular surgeons prescribed 5.47 +/- 2.26 drugs, medical doctors / angiologists 6.37 +/- 2.67 (p = 0.005). Overall, 239 (90.5 %) patients were on aspirin, 180 (68.2 %) on clopidogrel, and 18 (6.9 %) on oral anticoagulants. Significantly more patients treated by medical doctors / angiologists received clopidogrel (169 versus 11; p < 0.001), significantly more surgical patients received oral anticoagulants (11 versus 7; p = 0.016). The number of patients without prescriptions for any antithrombotic therapy was 6 (6.9 %) in patients treated by vascular surgeons and 0 (0 %) in patients managed by medical doctors / angiologists (p = 0.001). Prescription-rates of beta-blockers, ACE-inhibitors, Angiotensin II-antangonists, calcium channel blockers, and diuretics were statistically not different between the two disciplines, but statins were prescribed significantly more often by medical doctors / angiologists (139 versus 49; p < 0001). With the exceptions of Clopidogrel (women > men) and diuretics (men > women) we observed no gender-specific prescriptions. CONCLUSIONS: We observed high prescriptions rates of secondary medical prevention in patients primarily treated by medical doctors / angiologists and vascular surgeons. We believe that this result is highly influenced by our multidisciplinary approach. Nevertheless, efforts have to be made to raise vascular surgeons awareness of statin use and complete prescription of antithrombotic and antiplatelet drugs.


Subject(s)
Cardiovascular Agents/therapeutic use , Femoral Artery , Peripheral Vascular Diseases/drug therapy , Popliteal Artery , Practice Patterns, Physicians' , Secondary Prevention/methods , Vascular Surgical Procedures , Aged , Aged, 80 and over , Attitude of Health Personnel , Cooperative Behavior , Critical Pathways , Drug Prescriptions , Evidence-Based Medicine , Female , Germany , Guideline Adherence , Health Care Surveys , Health Knowledge, Attitudes, Practice , Hospitalization , Humans , Interdisciplinary Communication , Male , Patient Care Team , Peripheral Vascular Diseases/diagnosis , Peripheral Vascular Diseases/prevention & control , Practice Guidelines as Topic , Retrospective Studies , Treatment Outcome
13.
Vasa ; 38(4): 338-45, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19998254

ABSTRACT

BACKGROUND: Exploring patients' computer and internet use, their expectations and attitudes is mandatory for successful introduction of interactive online health-care applications in Angiology. PATIENTS AND METHODS: We included 165 outpatients suffering from peripheral arterial disease (PAD; n = 62) and chronic venous and / or lymphatic disease (CVLD; n = 103) in a cross-sectional-study. Patients answered a paper-based questionnaire. RESULTS: Patients were predominantly female (54.5%). 142 (86.1%) reported regular computer use for 9.7 +/- 5.8 years and 134 (81.2 %) used the internet for 6.2 +/- 3.6 years. CVLD-patients and internet-user were younger and higher educated, resulting in a significant difference in computer and internet use between the disease groups (p < 0.01 for both). Time spent online summed up to 4.3 +/- 2.2 days per week and 1.44 +/- 1.2 hours per day for all internet users without significant differences between the groups. The topics retrieved from the internet covered a wide spectrum and searches for health information were mentioned by 41.2 %. Although confidence in the internet (3.3 +/- 1.1 on a 1-6 Likert scale) and reliability in information retrieved from the internet (3.1 +/- 1.1) were relatively low, health-related issues were of high actual and future interest. 42.8% of the patients were even interested in interactive applications like health educational programs, 37.4% in self-reported assessments and outcome questionnaires and 26.9% in chatforums; 50% demanded access to their medical data on an Internetserver. Compared to older participants those < 50 yrs. used the internet more often for shopping, chatting, and e-mailing, but not for health information retrieval and interactive applications. CONCLUSIONS: Computers are commonly used and the internet has been adopted as an important source of information by patients suffering from PAD and CVLD. Besides, the internet offers great potentials and new opportunities for interactive disease (self-)management in angiology. To increase confidence and reliability in the medium a careful introduction and evaluation of these new online applications is mandatory.


Subject(s)
Attitude to Computers , Computer Literacy , Health Knowledge, Attitudes, Practice , Internet/statistics & numerical data , Lymphedema/therapy , Outpatients , Peripheral Vascular Diseases/therapy , Venous Insufficiency/therapy , Access to Information , Adult , Age Factors , Chronic Disease , Cross-Sectional Studies , Electronic Health Records/statistics & numerical data , Female , Humans , Information Dissemination , Leisure Activities , Lymphedema/psychology , Male , Middle Aged , Outpatients/psychology , Patient Education as Topic , Peripheral Vascular Diseases/psychology , Self Care/statistics & numerical data , Socioeconomic Factors , Surveys and Questionnaires , Time Factors , Venous Insufficiency/psychology , Young Adult
14.
Vasa ; 38(1): 39-45, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19229802

ABSTRACT

BACKGROUND: In this pilot study we examined circulating concentrations of nerve growth factor (NGF) in controls and patients suffering from primary or secondary Raynaud's syndrome and determined their relation to digital vasospasm. PATIENTS AND METHODS: Eighteen controls, 16 patients with primary RP and 19 patients with systemic sclerosis (SScl) were included. Degree of vasospasm was graduated according to the degree of plethysmographically measured vasospastic reaction after cold test. A diary was handed out for documentation of the daily number and duration of RP during a period of 16 days. Circulating NGF levels were analysed by a commercial ELISA (Promega Inc., USA). RESULTS: SScl-patients were significantly older (p < 0.0001) and more severely affected by spontaneously occurring RP (p = 0.03), whereas the severity of the vasospastic reactions after a standard cold test were not significantly different between the groups (p = 0.09). Within each study group and between the study groups elevated NGF levels were observed only in SScl-patients after thermal provocations (p = < 0.05). In a correlation analysis restricted to patients with PRP or SRP, the degree of vasospasm after cold testing as well as the intensity of Raynaud's symptoms were not correlated with NGF-levels (p = n.s.). CONCLUSIONS: Our results do not support the hypothesis that NGF plays a major role in the generation of vasospasm in Raynaud's phenomenon.


Subject(s)
Fingers/blood supply , Nerve Growth Factor/blood , Raynaud Disease/blood , Scleroderma, Systemic/complications , Vasoconstriction , Adult , Aged , Case-Control Studies , Cold Temperature , Enzyme-Linked Immunosorbent Assay , Humans , Middle Aged , Pilot Projects , Plethysmography , Raynaud Disease/etiology , Raynaud Disease/physiopathology , Scleroderma, Systemic/blood , Scleroderma, Systemic/physiopathology , Severity of Illness Index , Time Factors , Young Adult
15.
Rofo ; 180(12): 1110-6, 2008 Dec.
Article in German | MEDLINE | ID: mdl-18975249

ABSTRACT

PURPOSE: Application and verification of the Wells score for pre-test probability of deep vein thrombosis in the lower limbs in clinical routine. The goal was to reduce the number of immediate diagnostic measures for excluding vein thrombosis during acute investigation. New parameters for upgrading or modification the existing score were checked. MATERIALS AND METHODS: In a period from March through November 2007, 333 patients were assigned to the department of radiology in order to exclude deep vein thrombosis. A standardized questionnaire was used to identify the probability of deep vein thrombosis. The patients were categorized as low, moderate, and high risk. The examination was conducted with colored-coded duplex sonography. RESULTS: In the patient population of 333, 41 (12 %) had deep vein thrombosis of the lower limb. The prevalence was approximately 3 % in the low risk group, 34 % in the moderate risk group, and 63 % in the high risk group. Categorization with the Wells score is an instrument with high sensitivity (99.6 %) and specificity (100 %). CONCLUSION: The pre-test probability with the Wells score represents a useful and established instrument in the clinical routine. Acute examinations, especially during stand-by, can be reduced without neglecting patient safety. Patients with a Wells score of 0 don't require an acute examination. An elective investigation should be targeted. Patients with a score between 1 and 8 needed to be treated (within the next 24 hours) with KS and FKDS. According to on our data records, therapy should be started immediately for patients with a high risk of deep vein thrombosis.


Subject(s)
Emergencies , Probability , Ultrasonography, Doppler, Color/statistics & numerical data , Venous Thrombosis/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prospective Studies , Risk Assessment , Sensitivity and Specificity , Young Adult
16.
Rofo ; 180(9): 809-15, 2008 Sep.
Article in German | MEDLINE | ID: mdl-18690579

ABSTRACT

PURPOSE: The main problem when treating the superficial femoral and popliteal artery with PTA or stent implantation is the relatively high restenosis rate. Several ablative systems are available as an alternative. The purpose of this prospective study was to evaluate the safety and performance of a novel rotational and aspirating atherectomy system. MATERIALS AND METHODS: From June to December 2006, we treated 23 patients, median age 70.3 years (58-91), with the rotational atherectomy system. All patients had de-novo lesions of the SFA or PA with a minimum stenosis of 70%. According to the Rutherford classification, 39% of the patients were in category 2 and 61% in category 3. The median lesion length was 26.3 mm (5-100 mm). 26% of the patients had occlusions. RESULTS: The technical success rate was 100%. In 14 cases (61%) additional balloon dilatation was applied, in two cases stent implantation were performed. The median treatment duration with the device was 187.7 +/- 106.1 s (59-391 s). The aspirated volume was 116.5 +/- 72.0 ml. The ankle brachial index improved from preinterventional 0.60 +/- 0.16 to postinterventional 0.85 +/- 0.13 and after 6 month 0.80 +/- 0.13. During follow-up, two (8%) restenosis occurred. There were two complications, one dissection and one distal embolization. Follow-up could not be performed for two patients (8%). CONCLUSION: Atherectomy of femoropopliteal lesions with the Pathway PV Atherectomy System is very safe and effective. The low restenosis rate of 8% is promising, but there is still a lack of long-term results.


Subject(s)
Arterial Occlusive Diseases/therapy , Atherectomy, Coronary/instrumentation , Femoral Artery , Popliteal Artery , Aged , Aged, 80 and over , Angiography, Digital Subtraction , Arterial Occlusive Diseases/diagnosis , Catheterization , Combined Modality Therapy , Equipment Design , Female , Femoral Artery/pathology , Follow-Up Studies , Humans , Male , Middle Aged , Popliteal Artery/pathology , Prospective Studies , Recurrence , Stents , Ultrasonography, Doppler, Duplex
17.
Rofo ; 180(6): 547-52, 2008 Jun.
Article in German | MEDLINE | ID: mdl-18484516

ABSTRACT

PURPOSE: Mechanical thrombectomy has become a viable alternative to intra-arterial thrombolysis for the treatment of acute infrainguinal occlusion. The aim of this prospective study was to evaluate the safety and effectiveness of a mechanical thrombectomy system in comparison with ultrasound-enhanced thrombolysis. MATERIALS AND METHODS: From April 2005 to March 2007, 20 patients, mean age 67.4+/-13.6, with acute occlusions of the femoropopliteal bypass graft were treated with either a rotational thrombectomy system (Straub Rotarex, n=10) or with 1.0 mg/h Actilyse using an ultrasound-enhanced lysis system (EKOS Lysus Peripheral Catheter System, n=10). The mean occlusion length was 33.1 cm (range 28-40 cm) in the thrombectomy group and 33.7 cm (11-50 cm) in the lysis group. RESULTS: The technical success rate was 100% in the thrombectomy group and 90 % in the lysis group. The mean treatment time was significantly lower with 64.5 min (45-90 min) in the thrombectomy group in comparison with 904.0 min (120-1350 min) in the lysis group. The ankle brachial index (ABI) improved in the thrombectomy group from 0.41+/-0.09 to 0.86+/-0.10 at discharge and 0.85+/-0.07 after 1 month (p<0.05) and in the lysis group from preinterventional 0.37+/-0.15 to 0.82+/-0.16 at discharge and 0.80+/-0.24 after 1 month (p<0.05). In one case lysis had to be stopped after two hours because of dislocation of the introducer sheath which was then treated by open surgery. CONCLUSION: Mechanical-rotational thrombectomy with the Rotarex system and lysis with the ultrasound-enhanced catheter from Ekos were very safe and effective treatment options for acute occlusion. Blood flow is restored much faster with mechanical thrombectomy.


Subject(s)
Femoral Artery , Fibrinolytic Agents/therapeutic use , Graft Occlusion, Vascular/therapy , Ischemia/therapy , Popliteal Artery , Thrombectomy/instrumentation , Thrombolytic Therapy/instrumentation , Tissue Plasminogen Activator/therapeutic use , Ultrasonography, Interventional/instrumentation , Acute Disease , Adult , Aged , Aged, 80 and over , Equipment Design , Female , Femoral Artery/diagnostic imaging , Humans , Ischemia/diagnostic imaging , Male , Middle Aged , Outcome and Process Assessment, Health Care , Popliteal Artery/diagnostic imaging , Prospective Studies , Radiography
18.
Eur J Clin Microbiol Infect Dis ; 26(2): 141-5, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17216421

ABSTRACT

In a case-control study that included a total of 98 patients and 83 controls, the possible link between various pathogens and abdominal aortic aneurysms was investigated. For 68 patients with abdominal aortic aneurysm and age-matched controls, no differences were detected in the levels of immunoglobulin (Ig)A and IgG Chlamydiaceae and Chlamydophila pneumoniae antibodies. Patients with IgA titers positive for Chlamydophila pneumoniae showed progressive disease (defined as an annual increase of the aneurysm diameter of > or = 0.5 cm) more frequently than patients with negative IgA titers (p = 0.046). Polymerase chain reactions performed to detect DNA for Chlamydophila pneumoniae, Chlamydia trachomatis, Chlamydophila psittaci, human cytomegalovirus, Borrelia burgdorferi and Helicobacter pylori in tissue specimens of 30 patients and 15 controls were negative. In summary, Chlamydophila pneumoniae may contribute to aortic aneurysm disease progression, but DNA of this and other pathogens was not found in patients' specimens.


Subject(s)
Antibodies, Bacterial/blood , Aorta, Abdominal/microbiology , Aortic Aneurysm, Abdominal/microbiology , Chlamydiaceae/immunology , Chlamydophila pneumoniae/immunology , DNA, Bacterial/analysis , Aged , Aged, 80 and over , Case-Control Studies , Chlamydia Infections/immunology , Chlamydia Infections/microbiology , Chlamydiaceae/genetics , Chlamydiaceae/isolation & purification , Chlamydiaceae Infections/immunology , Chlamydiaceae Infections/microbiology , Chlamydophila pneumoniae/genetics , Chlamydophila pneumoniae/isolation & purification , Female , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Male
19.
Vasa ; 35(1): 41-4, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16535969

ABSTRACT

We report two cases of femoral vein thrombosis after arterial PTA and subsequent pressure stasis. We discuss the legal consequences of these complications for information policies. Because venous thrombembolism following an arterial PTA might cause serious sequel or life threatening complications, there is a clear obligation for explicit information of the patients about this rare complication.


Subject(s)
Angioplasty, Balloon/adverse effects , Arterial Occlusive Diseases/therapy , Femoral Artery , Femoral Vein , Venous Thrombosis/etiology , Aged, 80 and over , Anticoagulants/therapeutic use , Disclosure , Female , Humans , Informed Consent , Male , Middle Aged , Ultrasonography , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/drug therapy
20.
Eur J Vasc Endovasc Surg ; 26(2): 161-5, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12917831

ABSTRACT

OBJECTIVES: to determine medium term technical and clinical success of kissing stents for aortoiliac occlusive disease. DESIGN: retrospective study. SUBJECTS: twenty-five patients presenting with intermittent claudication (IC) or critical limb ischaemia (CLI) due to aortoiliac disease (41 complex stenoses, 8 occlusions). METHODS: balloon- or self-expanding kissing stents, with or without predilatation depending upon the nature of the disease, were inserted via bilateral retrograde femoral artery punctures. Clinical examination, ABPI, exercise testing and duplex ultrasound were performed at 1, 3, 6, and 12 months, and then annually. RESULTS: technical success was achieved in 86% segments. All patients with CLI improved and 6 of 7 ulcerated limbs showed complete healing. During follow-up, 7 patients died and two patients required major amputation at 7 and 8 months. The primary assisted patency rate was 94, 91 and 65% at 6, 12, and 24 months, respectively. CONCLUSIONS: despite acceptable short-term technical and clinical success, as the medium term patency rates are clearly inferior to those of bypass surgery, the kissing stent technique should be reserved for high risk patients with a limited life expectancy.


Subject(s)
Aortic Diseases/therapy , Arterial Occlusive Diseases/therapy , Iliac Artery , Stents , Female , Humans , Intermittent Claudication/etiology , Intermittent Claudication/therapy , Ischemia/etiology , Ischemia/therapy , Leg/blood supply , Male , Prosthesis Design , Treatment Outcome
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