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1.
Neurourol Urodyn ; 40(7): 1820-1828, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34342363

RESUMO

AIMS: To evaluate the efficacy, sustainability and safety of combined botulinum toxin and polyacrylamide hydrogel (PAHG) therapy to treat urgency and stress components of therapy-refractory mixed urinary incontinence (MUI) in an elderly study population. METHODS: Fifty-five women with therapy-refractory MUI were treated with botulinum toxin and PAHG in one surgical procedure. Urgency urinary incontinence (UUI) and stress urinary incontinence (SUI) outcomes were separately assessed after 4 and 12 months by objective UUI episodes/24 h and cough test, subjective impact of UUI and SUI on quality of life, and subjective International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF). MUI outcome was calculated by combining UUI and SUI outcomes. Complications were monitored throughout the study. RESULTS: At 4 months, objective cure rates were 73%, 53%, and 42%, and subjective cure rates were 71%, 52%, and 50% for SUI, UUI, and MUI. At 12 months, objective cure rates were 73%, 56%, 50% and subjective cure rates were 78%, 42%, and 40% for SUI, UUI, and MUI. The ICIQ-UI SF score decreased by 9.0 and 8.7 points after 4 and 12 months. All complications were transient and included 22% clean intermittent catheterization immediately after surgery, 33% postvoid residual volumes >100 ml at 14 days, and 13% symptomatic urinary tract infection within the first postoperative month. CONCLUSIONS: The combination of botulinum toxin and PAHG is effective, sustainable and safe to treat therapy-refractory MUI, even in an elderly and frail study population. Patients benefit from the short surgical procedure without the need for general anaesthesia or discontinuation of anticoagulation.


Assuntos
Toxinas Botulínicas , Incontinência Urinária por Estresse , Incontinência Urinária , Idoso , Feminino , Humanos , Qualidade de Vida , Resultado do Tratamento , Incontinência Urinária/tratamento farmacológico , Incontinência Urinária por Estresse/tratamento farmacológico , Incontinência Urinária de Urgência/tratamento farmacológico
2.
Undersea Hyperb Med ; 46(1): 45-53, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31154684

RESUMO

Background: Perianal fistulizing Crohn's disease (pCD) has a significant impact on patients' health and quality of life. Current treatment options have a relatively low success rate and a high recurrence risk. Positive effects of hyperbaric oxygen (HBO2) therapy have been indicated in animal studies as well as in small case series. Methods/Design: This is a non-randomized, controlled pilot study. A total of 20 patients with pCD who have been refractory to standard therapy for at least six months will be included. Patients with a seton and stable treatment regimen will be included. Patients with anal strictures, rectovaginal fistulas, stoma or deep ulceration of the rectum will be excluded. Patients who are eligible but refuse HBO2 will be asked to serve as controls. Patients in the HBO2 group will be treated with 40 sessions of HBO2 therapy at 243-253 kPa, with the seton being removed after 30 sessions. Co-primary endpoints are changes in the perianal disease activity index and MRI-scores. Secondary outcomes are fistula drainage assessment, laboratory findings and patient-reported outcomes. Assessment will be done at baseline, 16 weeks, 34 weeks and 60 weeks after finishing HBO2. Discussion: The aim of this study is to investigate the feasibility and therapeutic effect of HBO2 on pCD. The one-year follow-up should provide information on the effect durability. A comparison between patients treated with HBO2 and patients who continue to receive standard care will be made. The risk of bias will be limited by using clearly defined inclusion and exclusion criteria, baseline characteristics and consecutive recruitment of patients through an outpatient fistula clinic. Trial registration: The HOT-TOPIC trial has been approved by the local Medical Ethical Committee of the Academic Medical Centre in Amsterdam, the Netherlands. The trial has been registered at the Netherlands Trial Register (www.trialregister.nl), registration number: NTR 6676. Protocol version: August 2017, version 3.0.


Assuntos
Ensaios Clínicos Controlados como Assunto , Doença de Crohn/complicações , Oxigenoterapia Hiperbárica , Fístula Retal/terapia , Estudos de Viabilidade , Seguimentos , Humanos , Projetos Piloto , Estudos Prospectivos , Fístula Retal/etiologia , Tamanho da Amostra , Fatores de Tempo
3.
Z Rheumatol ; 75(7): 729-35, 2016 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-27193336

RESUMO

Systemic mastocytosis is defined as a clonal increase of mast cells. We report on four patients with severe osteoporosis and histologically confirmed systemic mastocytosis. In spite of antiresorptive therapy the patients developed further vertebral fractures and suffered from ostealgia. Systemic mastocytosis is an important differential diagnosis in patients with therapy refractive and unexplained osteoporosis. Skin involvement (urticaria pigmentosa) is a rare occurrence and in most cases an isolated involvement of bone marrow is present. Determination of serum tryptase can provide indications for systemic mastocytosis but the diagnosis is only confirmed by bone marrow biopsy. There is a high risk of vertebral fractures and patients should be treated in specialized centers. Zoledronic acid can be a therapeutic option for indolent osteoporosis associated with systemic mastocytosis.


Assuntos
Anti-Inflamatórios/uso terapêutico , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/tratamento farmacológico , Osteoporose/diagnóstico , Osteoporose/tratamento farmacológico , Adulto , Conservadores da Densidade Óssea/uso terapêutico , Doença Crônica , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Mastocitose Sistêmica/complicações , Pessoa de Meia-Idade , Doenças Raras/diagnóstico , Falha de Tratamento , Resultado do Tratamento , Ácido Zoledrônico
4.
Brain Behav Immun Health ; 35: 100717, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38186634

RESUMO

Recent observations suggest a role of the volume of the cerebral ventricle volume, corpus callosum (CC) segment volume, in particular that of the central-anterior part, and choroid plexus (CP) volume for treatment resistance of major depressive disorder (MDD). An increased CP volume has been associated with increased inflammatory activity and changes in the structure of the ventricles and corpus callosum. We attempt to replicate and confirm that these imaging markers are associated with clinical outcome in subjects from the EMBARC study, as implied by a recent pilot study. The EMBARC study is a placebo controlled randomized study comparing sertraline vs. placebo in patients with MDD to identify biological markers of therapy resistance. Association of baseline volumes of the lateral ventricles (LVV), choroid plexus volume (CPV) and volume of segments of the CC with treatment response after 4 weeks treatment was evaluated. 171 subjects (61 male, 110 female) completed the 4 week assessments; gender and age were taken into account for this analyses. As previously reported, no treatment effect of sertraline vs. placebo was observed, therefore the study characterized prognostic markers of response in the pooled population. Change in depression severity was identified by the ratio of the Hamilton-Depression rating scale 17 (HAMD-17) at week 4 divided by the HAMD-17 at baseline (HAMD-17 ratio). Volumes of the lateral ventricles and choroid plexi were positively correlated with the HAMD-17 ratio, indication worse outcome with larger ventricles and choroid plexus volumes, whereas the volume of the central-anterior corpus callosum was negatively correlated with the HAMD-17 ratio. Responders (n = 54) had significantly smaller volumes of the lateral ventricles and CP compared to non-responders (n = 117), whereas the volume of mid-anterior CC was significantly larger compared to non-responders (n = 117), confirming our previous findings. In an exploratory way associations between enlarged LVV and CPV and signs of lipid dysregulation were observed. In conclusion, we confirmed that volumes of lateral ventricles, choroid plexi and the mid-anterior corpus callosum are associated with clinical improvement of depression and may be indicators of metabolic/inflammatory activity.

5.
Heart Fail Clin ; 9(4): 489-99, ix, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24054481

RESUMO

Ablation of the atrioventricular junction (AVJ) is a technically easy procedure that is safe and has a high success rate as an intervention for effective ventricular rate control in patients in symptomatic atrial fibrillation. AVJ ablation has been reported to improve quality of life, left ventricular ejection fraction, and exercise duration in these patients and minimize the incidence of inappropriate shocks. Because right ventricular pacing after AVJ ablation may result in decrease in left ventricular function and worsening of heart failure symptoms, there is increasing evidence to support the effectiveness of cardiac resynchronization therapy in atrial fibrillation populations.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Sistema de Condução Cardíaco/fisiopatologia , Insuficiência Cardíaca/complicações , Função Ventricular Esquerda , Fibrilação Atrial/complicações , Fibrilação Atrial/fisiopatologia , Sistema de Condução Cardíaco/cirurgia , Insuficiência Cardíaca/fisiopatologia , Humanos
6.
PNAS Nexus ; 2(6): pgad203, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37388923

RESUMO

Diverse cellular activities are modulated through a variety of RNAs, including long noncoding RNAs (lncRNAs), by binding to certain proteins. The inhibition of oncogenic proteins or RNAs is expected to suppress cancer cell proliferation. We have previously demonstrated that PSF interaction with its target RNAs, such as androgen-induced lncRNA CTBP1-AS, is critical for hormone therapy resistance in prostate and breast cancers. However, the action of protein-RNA interactions remains almost undruggable to date. High-throughput screening (HTS) has facilitated the discovery of drugs for protein-protein interactions. In the present study, we developed an in vitro alpha assay using Flag peptide-conjugated lncRNA, CTBP1-AS, and PSF. We then constructed an effective HTS screening system to explore small compounds that inhibit PSF-RNA interactions. Thirty-six compounds were identified and dose-dependently inhibited PSF-RNA interaction in vitro. Moreover, chemical optimization of these lead compounds and evaluation of cancer cell proliferation revealed two promising compounds, N-3 and C-65. These compounds induced apoptosis and inhibited cell growth in prostate and breast cancer cells. By inhibiting PSF-RNA interaction, N-3 and C-65 up-regulated signals that are repressed by PSF, such as the cell cycle signals by p53 and p27. Furthermore, using a mouse xenograft model for hormone therapy-resistant prostate cancer, we revealed that N-3 and C-65 can significantly suppress tumor growth and downstream target gene expression, such as the androgen receptor (AR). Thus, our findings highlight a therapeutic strategy through the development of inhibitors for RNA-binding events in advanced cancers.

7.
Inflamm Bowel Dis ; 28(4): 611-621, 2022 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-34003289

RESUMO

BACKGROUND: Accumulating evidence suggests that hyperbaric oxygen therapy (HBOT) may be effective for inflammatory bowel disease (IBD). Our systematic review aimed to quantify the effectiveness and safety of HBOT in various IBD phenotypes. METHODS: We performed a proportional meta-analysis. Multiple databases were systematically searched from inception through November 2020 without language restriction. We included studies that reported effectiveness and/or safety of HBOT in IBD. Weighted summary estimates with 95% confidence intervals (Cis) were calculated for clinical outcomes for each IBD phenotype using random-effects models. Study quality was assessed using the Cochrane evaluation handbook and National Institute of Health criteria. RESULTS: Nineteen studies with 809 patients total were eligible: 3 randomized controlled trials and 16 case series. Rates of clinical remission included 87% (95% CI, 10-100) for ulcerative colitis (n = 42), 88% (95% CI, 46-98) for luminal Crohn's disease (CD, n = 8), 60% (95% CI, 40-76) for perianal CD (n = 102), 31% (95% CI, 16-50) for pouch disorders (n = 60), 92% (95% CI, 38-100) for pyoderma gangrenosum (n = 5), and 65% (95% CI, 10-97) for perianal sinus/metastatic CD (n = 7). Of the 12 studies that reported on safety, 15% of patients (n = 30) had minor adverse events. Study quality was low in the majority of studies due to an absence of comparator arms, inadequate description of concomitant interventions, and/or lack of objective outcomes. CONCLUSIONS: Limited high-quality evidence suggests that HBOT is safe and associated with substantial rates of clinical remission for multiple IBD phenotypes. Well-designed randomized controlled trials are warranted to confirm the benefit of HBOT in IBD.


Assuntos
Colite Ulcerativa , Doença de Crohn , Oxigenoterapia Hiperbárica , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Humanos , Oxigenoterapia Hiperbárica/efeitos adversos , Fenótipo
8.
United European Gastroenterol J ; 10(2): 160-168, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35146959

RESUMO

BACKGROUND: Previously published short-term results (week 16) of this trial showed a significant improvement in clinical, radiologic and biochemical outcomes in Crohn's disease patients with therapy-refractory perianal fistulas after treatment with hyperbaric oxygen therapy. OBJECTIVE: To assess the long-term (week 60) efficacy, safety and feasibility of hyperbaric oxygen therapy in perianal fistula in Crohn's disease. METHODS: Crohn's disease patients with high perianal fistula(s) failing conventional treatment >6 months were included. Exclusion criteria were presence of a stoma, rectovaginal fistula(s) and recent changes in treatment regimens. Patients received 40 hyperbaric oxygen sessions and outcomes were assessed at week 16 and week 60. RESULTS: Twenty patients were included (median age 34 years). At week 16, median scores of the perianal disease activity index and modified Van Assche index (co-primary outcomes) decreased from 7.5 (95% CI 6-9) to 4 (95% CI 3-6, p < 0.001) and 9.2 (95% CI 7.3-11.2) to 7.3 (95% CI 6.9-9.7, p = 0.004), respectively. At week 60, the respective scores remained significantly lower than baseline: 4 (95% CI 3-7, p < 0.001) and 7.7 (95% CI 5.2-10.2, p = 0.003). Perianal disease activity index score of 4 or less (representing inactive perianal disease) was observed in 13 patients at week 16 and 12 patients at week 60. Using fistula drainage assessment, 12 and 13 patients showed a clinical response at week 16 and 60, respectively, and clinical remission was achieved in four patients for both time points. At week 16, a statistically significant biochemical improvement (C-reactive protein and faecal calprotectin levels) was found, but this effect was no longer significant at week 60. CONCLUSIONS: The clinical and radiologic improvement of perianal fistula in Crohn's disease, that was found at week 16 after treatment with hyperbaric oxygen therapy, is maintained at 1-year follow-up.


Assuntos
Doença de Crohn , Oxigenoterapia Hiperbárica , Fístula Retal , Adulto , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Feminino , Seguimentos , Humanos , Fístula Retal/diagnóstico , Fístula Retal/etiologia , Fístula Retal/terapia , Resultado do Tratamento
9.
Immune Netw ; 20(1): e7, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32158595

RESUMO

Cancer immunotherapy, in the form of vaccination, adoptive cellular transfer, or immune checkpoint inhibitors, has emerged as a promising practice within the field of oncology. However, despite the developing field's potential to revolutionize cancer treatment, the presence of immunotherapeutic-resistant tumor cells in many patients present a challenge and limitation to these immunotherapies. These cells not only indicate immunotherapeutic resistance, but also show multi-modal resistance to conventional therapies, abnormal metabolism, stemness, and metastasis. How can immunotherapeutic-resistant tumor cells render multi-malignant phenotypes? We reasoned that the immune-refractory phenotype could be associated with multi-malignant phenotypes and that these phenotypes are linked together by a factor that acts as the master regulator. In this review, we discussed the role of the embryonic transcription factor NANOG as a crucial master regulator we named "common factor" in multi-malignant phenotypes and presented strategies to overcome multi-malignancy in immunotherapeutic-resistant cancer by restraining the NANOG-mediated multi-malignant signaling axis. Strategies that blunt the NANOG axis could improve the clinical management of therapy-refractory cancer.

10.
Pharmacol Ther ; 205: 107422, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31626872

RESUMO

Epilepsies represent one of the most common neurological diseases worldwide. They are characterized by recurrent spontaneous seizures with severe impact on a patient's life. An imbalance in excitatory and inhibitory signalling is considered the main underlying pathophysiological mechanism. Therefore, GABA-mimetic drugs, strengthening the main inhibitory signalling system in the CNS, are frequently used as antiepileptic or anticonvulsant drugs. However, the therapeutic effect of such treatment depends on the chloride gradient along the plasma membrane. Impairment of chloride homeostasis, caused by alterations in the functional balance of chloride transporters, was implicated in the pathophysiology of epilepsy and numerous other diseases. Breakdown or even inversion of the chloride gradient may result in ineffective or in worst cases proconvulsant effects of GABA-mimetics. Unfortunately, such situations are reported in considerable number. Consequently, bumetanide, an inhibitor of Na-K-Cl cotransporters gained interest as potential add-on therapy re-establishing the chloride gradient and thereby the hyperpolarizing effects of GABA-mimetic drugs. Indeed, preclinical studies yielded encouraging results, especially when applied in combination with GABA-mimetics in epilepsy models. However, bumetanide induces a strong diuretic effect and displays poor penetration across the blood-brain barrier, two adverse features for chronic antiepileptic treatment. Therefore, new compounds overcoming these limitations are under development. This review focuses on alterations in chloride homeostasis and its underlying molecular mechanisms in epilepsy, on the potential impact of impaired chloride homeostasis on the treatment of epilepsy and on concepts to overcome this problem including recent development of bumetanide derivatives with improved pharmacological profile.


Assuntos
Anticonvulsivantes/farmacologia , Cloretos/metabolismo , Epilepsia/tratamento farmacológico , Animais , Anticonvulsivantes/efeitos adversos , Barreira Hematoencefálica , Bumetanida/efeitos adversos , Bumetanida/farmacocinética , Bumetanida/farmacologia , Diuréticos/efeitos adversos , Diuréticos/farmacocinética , Diuréticos/farmacologia , Desenvolvimento de Medicamentos , Epilepsia/fisiopatologia , Humanos , Inibidores de Simportadores de Cloreto de Sódio e Potássio/efeitos adversos , Inibidores de Simportadores de Cloreto de Sódio e Potássio/farmacocinética , Inibidores de Simportadores de Cloreto de Sódio e Potássio/farmacologia , Distribuição Tecidual
11.
Clin Ophthalmol ; 12: 1301-1309, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30050283

RESUMO

PURPOSE: The objective of the study was to assess the effect of off-label photodynamic therapy (PDT) in combination with intravitreal off-label ziv-aflibercept or off-label aflibercept injection in patients with chronic or repeatedly recurrent acute central serous chorioretinopathy (CSC). PATIENTS AND METHODS: Changes in best corrected visual acuity (BCVA) and subfoveal subretinal fluid (sSRF) and maximum subretinal fluid (mSRF) were retrospectively analyzed in a single-center cohort study of 17 patients (18 eyes) with persistent subretinal fluid for more than 3 months of duration of CSC. Treatment efficacy was measured between injection and PDT at 30±15 days, 90±15 days and 180±30 days after PDT. RESULTS: Significant reduction of sSRF and mSRF was shown after therapy with ziv-aflibercept and aflibercept combined with PDT (p<0.001). Course of BCVA showed non-significant improvement within 6 months (p=0.065). One case of allergic reaction after fluorescein angiography and one case of ophthalmic migraine after ziv-aflibercept injection were documented. One case of reversible vision loss occurred during 6 months after combination therapy. No other adverse events or side effects were reported. CONCLUSION: Combination therapy of ziv-aflibercept and aflibercept with PDT seems to be beneficial, even in cases of chronic or repeatedly recurrent acute CSC. This includes cases of CSC resistant to or recurrent after medical treatment, PDT alone or therapy with anti-vascular endothelial growth factor alone.

12.
Cardiovasc Endocrinol ; 6(2): 81-85, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28540139

RESUMO

INTRODUCTION: Hypercholesterolemia is a causal risk factor for cardiovascular diseases, which is recommended to be treated at least in high-risk patients. Yet, currently there is a lack of epidemiological data on the number of high-risk patients in Germany who do not respond adequately to high-dose statin monotherapy or statin therapy in combination with other lipid-lowering agents. METHODS: Of a total of over 2.6 million patient records from general practitioners in the IMS Disease Analyzer database, all high-risk cardiovascular patients with hypercholesterolemia who did not reach target low-density lipoprotein-cholesterol (LDL-C) levels despite at least 12 months of maximum lipid-lowering therapy and optimal medication supply (medication possession rate≥80%) were selected over a defined period. RESULTS: On the basis of the practice data, a total of 602 133 patients with a high cardiovascular risk who were treated with statin monotherapy or statin combination therapy with optimal medication supply (medication possession rate≥80%) for at least 12 months were identified. Of them, 49 406 patients received high-dose statin therapy, and 51 869 patients received statin therapy in any dose in combination with another lipid-lowering agent. A total of 79 848 high-risk patients did not reach the target LDL-C level of 70 mg/dl or less despite consistent lipid-lowering therapy; of them, 12 808 had a documented LDL-C level of at least 130 mg/dl. CONCLUSION: The prevalence of high-risk cardiovascular patients with therapy-resistant hypercholesterolemia is substantial in Germany.

13.
J Am Soc Hypertens ; 10(6): 490-2, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27184290

RESUMO

Clinical trials have demonstrated significant and durable reduction in arterial pressure from baroreflex activation therapy (BAT) in patients with resistant arterial hypertension. There is a lack of data, however, concerning the use of BAT in a rescue approach during therapy-refractory hypertensive crisis resulting in life-threatening end-organ damage. Here, we describe the first case in which BAT was applied as a rescue procedure in an intensive care setting after ineffective maximum medical treatment. A 34-year-old male patient presented with Stanford B aortic dissection and hypertensive crisis. The dissection membrane extended from the left subclavian artery down to the right common iliac artery, resulting in a total arterial occlusion of the right leg. After emergency thoracic endovascular aortic repair and femorofemoral crossover bypass, the patient developed a compartment syndrome of the right lower limb, ultimately leading to amputation of the right leg above the knee. Even under deep sedation recurrent hypertensive crises of up to 220 mm Hg occurred that could not be controlled by eight antihypertensive drugs of different classes. Screening for secondary hypertension was negative. Eventually, rescue implantation of right-sided BAT was performed as a bailout procedure, followed by immediate activation of the device. After a hospital stay of a total of 8 weeks, the patient was discharged 2 weeks after BAT initiation with satisfactory blood pressure levels. After 1-year follow-up, the patient has not had a hypertensive crisis since the onset of BAT and is currently on fourfold oral antihypertensive therapy. The previously described bailout procedures for the treatment of life-threatening hypertensive conditions that are refractory to drug treatment have mainly comprised the interventional denervation of renal arteries. The utilization of BAT is new in this emergency context and showed a significant, immediate, and sustained reduction of blood pressure levels after activation. To our knowledge, we report the first case of an immediate activation of a barostim while the device is usually not activated before 2 to 4 weeks after implantation to allow time for the surgical site to heal. During the follow-up period, the healing process was not impaired, and a significant, immediate, and sustained reduction of blood pressure levels after activation could be observed. This treatment option offers maximum adherence to antihypertensive therapy to avoid future cardiovascular end-organ damage and possibly reduce antihypertensive medication and undesirable side effects.


Assuntos
Anti-Hipertensivos/uso terapêutico , Dissecção Aórtica/cirurgia , Barorreflexo , Vasoespasmo Coronário/terapia , Cuidados Críticos/métodos , Terapia por Estimulação Elétrica/métodos , Hipertensão/terapia , Adulto , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/etiologia , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/cirurgia , Pressão Sanguínea , Determinação da Pressão Arterial , Seio Carotídeo/fisiologia , Angiografia por Tomografia Computadorizada , Vasoespasmo Coronário/complicações , Terapia por Estimulação Elétrica/instrumentação , Procedimentos Endovasculares , Humanos , Hipertensão/complicações , Masculino
14.
J Pediatr Urol ; 11(3): 119.e1-6, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25794865

RESUMO

INTRODUCTION: An increased activity of the external urethral sphincter or pelvic floor muscles during voluntary voiding leads to dysfunctional voiding. Frequently reported symptoms are urinary incontinence, urinary tract infections and high post-void residuals. Dysfunctional voiding is a common problem in school-aged children and despite various treatment options, 10-40% of the children remain therapy-refractory. OBJECTIVE: The aim of this study is to evaluate the effectiveness of Onabotulinum toxin-A (BTX-A) injections in the external urethral sphincter in children with therapy-refractory dysfunctional voiding. PATIENTS AND METHODS: Patients with therapy-refractory dysfunctional voiding who have received BTX-A injections in the external urethral sphincter from 2010 to 2013 were analysed. Children with known neuropsychiatric disorders were excluded. All children had abnormal flow patterns and increased pelvic floor tone during uroflowmetry/EMG studies. They had received at least five sessions of urotherapy and two sessions of pelvic floor physical therapy prior to treatment. A total of 100 IU of BTX-A was injected in the external urethral sphincter at the 3, 9 and 12 o'clock positions. Our main outcome measures were urinary incontinence, recurrent urinary tract infections and post-void residual. RESULTS: A total of twenty patients, of whom 16 girls, with a median age of 9 years (range 5-14) were treated with BTX-A. The median follow-up was 13 months (range 5-34). Post-void residual decreased by 75% after BTX-A, from a median of 47.5 ml (16.3-88.5 ml) to 0 ml (0.0-28.0 ml) (p = 0.001) Six patients had a post-void residual < 20 ml prior to treatment. After BTX-A sixteen patients had a post-void residual <20 ml (Figure). No significant changes in uroflowmetry results was seen. Sixteen children are no longer daily incontinent, of whom 9 became completely dry (p = 0.0001). Eleven patients suffered from recurrent urinary tract infections prior to treatment. After BTX-A five children remained infection free, while the other six experienced only one urinary tract infection during follow-up (p = 0.003). Fourteen patients received additional urotherapy after BTX-A. Repeat injections were necessary in four patients after initial satisfactory results, with repeated good clinical responses. Two children showed no improvement after first BTX-A injection. No serious adverse events were reported. DISCUSSION: The results in this homogenous group of patients confirm the conclusions of previous studies in opting BTX-A in the external urethral sphincter to be a viable treatment option for the therapy-refractory group of patients with dysfunctional voiding. What is new, is that in most of our patients post-injection urotherapy was used to amplify the BTX-A effect. During our long-term follow-up the satisfactory results were sustained, similar to the results of the long-term follow-up presented by Vricella et al. [1]. The retrospective character and relative small sample size are limitations of this study. CONCLUSIONS: This study shows safe and persistent satisfactory results during our average 13-month follow-up in 90% of our patients with therapy-refractory dysfunctional voiding. A prospective study using validated and standardized measurements will be performed to affirm our results and evaluate the exact role of post-injection urotherapy.


Assuntos
Inibidores da Liberação da Acetilcolina/uso terapêutico , Toxinas Botulínicas Tipo A/uso terapêutico , Transtornos Urinários/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Injeções , Masculino , Resultado do Tratamento , Uretra
15.
World J Transplant ; 5(4): 354-9, 2015 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-26722664

RESUMO

In liver haemangiomas, the risk of complication rises with increasing size, and treatment can be obligatory. Here we present a case of a 46-year-old female who suffered from a giant haemangioma causing severe portal hypertension and vena cava compression, leading to therapy refractory ascites, hyponatremia and venostasis-associated thrombosis with pulmonary embolism. The patients did not experience tumour rupture or consumptive coagulopathy. Surgical resection was impossible because of steatosis of the non-affected liver. Orthotopic liver transplantation was identified as the only treatment option. The patient's renal function remained stable even though progressive morbidity and organ allocation were improbable according to the patient's lab model for end-stage liver disease (labMELD) score. Therefore, non-standard exception status was approved by the European organ allocation network "Eurotransplant". The patient underwent successful orthotopic liver transplantation 16 mo after admission to our centre. Our case report indicates the underrepresentation of morbidity associated with refractory ascites in the labMELD-based transplant allocation system, and it indicates the necessity of promptly applying for non-standard exception status to enable transplantation in patients with a severe clinical condition but low labMELD score. Our case highlights the fact that liver transplantation should be considered early in patients with non-resectable, symptomatic benign liver tumours.

17.
Clin Neurol Neurosurg ; 115(8): 1245-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23266263

RESUMO

OBJECTIVE: We present a series of 87 patients who underwent anteromesial temporal lobe resections for therapy refractory temporal lobe epilepsy. In addition to seizure outcome, we observed excessively elevated CRP-levels in this patient population. METHODS: We followed 87 patients (m=39, f=48; mean age 33.73±12.92, range 5-67 years) who underwent surgery between July 2003 and November 2011. Seizure outcome was classified in all patients according to the ILAE-classification by Wieser et al. (mean follow-up: 38.72 months). CRP levels were measured in 59 patients of the epilepsy surgery group and in a control group of 44 consecutive patients with supratentorial tumors (22 glioblastomas, 22 meningiomas). RESULTS: Clinical benefit was seen in 96.6% of the patients (ILAE classes 1-4), 80.5% were completely seizure free (ILAE class 1). Post-OP CRP values were significantly higher in the epilepsy group (n=59; mean CRP peak value: 100.86 mg/l, range: 16-258 mg/l) compared to the control group (n=44; mean CRP peak value: 36.85 mg/l, range: 0.4-233 mg/l) (p<0.001), but the correlation of mean CRP value and mean temperature peak is weak (r=0.31). CONCLUSIONS: Seizure outcome after surgery for temporal lobe epilepsy was excellent, CRP levels were excessively elevated in these patients in the absence of clinical infection and significantly higher compared to resections of supratentorial lesions.


Assuntos
Proteína C-Reativa/metabolismo , Epilepsia do Lobo Temporal/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/metabolismo , Adolescente , Adulto , Idoso , Tonsila do Cerebelo/cirurgia , Anticonvulsivantes/uso terapêutico , Química Encefálica , Criança , Pré-Escolar , Resistência a Medicamentos , Feminino , Hipocampo/cirurgia , Humanos , Inflamação/patologia , Cinética , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Estudos Retrospectivos , Convulsões/tratamento farmacológico , Convulsões/epidemiologia , Neoplasias Supratentoriais/cirurgia , Resultado do Tratamento , Adulto Jovem
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