A quarter of a century biomechanical rupture risk assessment of abdominal aortic aneurysms. Achievements, clinical relevance, and ongoing developments.

Abdominal aortic aneurysm (AAA) disease, the local enlargement of the infrarenal aorta, is a serious condition that causes many deaths, especially in men exceeding 65 years of age. Over the past quarter of a century, computational biomechanical models have been developed towards the assessment of AAA risk of rupture, technology that is now on the verge of being integrated within the clinical decision-making process. The modeling of AAA requires a holistic understanding of the clinical problem, in order to set appropriate modeling assumptions and to draw sound conclusions from the simulation results. In this article we summarize and critically discuss the proposed modeling approaches and report the outcome of clinical validation studies for a number of biomechanics-based rupture risk indices. Whilst most of the aspects concerning computational mechanics have already been settled, it is the exploration of the failure properties of the AAA wall and the acquisition of robust input data for simulations that has the greatest potential for the further improvement of this technology.

Increasing prevalence of ciprofloxacin resistance in extended-spectrum-ß-lactamase-producing Escherichia coli urinary isolates.

PURPOSE: To describe the incidence and drug susceptibility profiles of uropathogenic extended-spectrum-ß-lactamase-producing Escherichia coli (ESBL-EC) during a 10-year period and to identify differences in resistance patterns between urological and non-urological ESBL-EC isolates. METHODS: Retrospective analysis of 191,564 urine samples obtained during 2001 to 2010 at the University Hospital Basel, Switzerland. The computerized database of the Clinical Microbiology Laboratory and the Division of Infectious Diseases and Hospital Epidemiology was used to identify ESBL-EC positive urine samples. ESBL-EC isolates were stratified according their origin into two groups: Urology and non-Urology isolates. RESULTS: The rate of ESBL-EC positive urine samples increased significantly during the study period (3 in 2001 compared to 55 in 2010, p < 0.05). The most active agents were imipenem, meropenem, and fosfomycin (100%), followed by amikacin (99.1%) and nitrofurantoin (84%). The least active substances were ampicillin-clavulanate (20%), sulfamethoxazole (28%), and ciprofloxacin (29.6%). ESBL-EC isolates from urological and non-urological patients showed similar susceptibility profiles. However, ESBL-EC isolates from urological patients were significantly less susceptible to ciprofloxacin compared to non-urological isolates (14.7 vs. 32.7%, p < 0.05). CONCLUSIONS: The rate of urinary ESBL-EC isolates is increasing. Their susceptibility to nitrofurantoin, fosfomycin, and carbapenems is excellent, whereas ampicillin-clavulanate, sulfamethoxazole, and ciprofloxacin demonstrate only low susceptibility. In particular, the use of ciprofloxacin should be strictly avoided in urologic patients with suspicion for an ESBL-EC urinary tract infection as well as routine antibiotic prophylaxis prior to urological interventions if not explicit indicated by current international guidelines or local resistance patterns.

Cerebral somatic pain modulation during autogenic training in fMRI.

BACKGROUND: Functional magnetic resonance imaging (fMRI) studies are increasingly employed in different conscious states. Autogenic training (AT) is a common clinically used relaxation method. The purpose of this study was to investigate the cerebral modulation of pain activity patterns due to AT and to correlate the effects to the degree of experience with AT and strength of stimuli. METHODS: Thirteen volunteers familiar with AT were studied with fMRI during painful electrical stimulation in a block design alternating between resting state and electrical stimulation, both without AT and while employing the same paradigm when utilizing their AT abilities. The subjective rating of painful stimulation and success in modulation during AT was assessed. RESULTS: During painful electrical stimulation without AT, fMRI revealed activation of midcingulate, right secondary sensory, right supplementary motor, and insular cortices, the right thalamus and left caudate nucleus. In contrast, utilizing AT only activation of left insular and supplementary motor cortices was revealed. The paired t-test revealed pain-related activation in the midcingulate, posterior cingulate and left anterior insular cortices for the condition without AT, and activation in the left ventrolateral prefrontal cortex under AT. Activation of the posterior cingulate cortex and thalamus correlated with the amplitude of electrical stimulation. CONCLUSIONS: This study revealed an effect on cerebral pain processing while performing AT. This might represent the cerebral correlate of different painful stimulus processing by subjects who are trained in performing relaxation techniques. However, due to the absence of a control group, further studies are needed to confirm this theory.

Occipital nerve stimulation for the treatment of chronic cluster headache - lessons learned from 18 months experience.

OBJECTIVE: Neuromodulation has been recognized as a valuable surgical treatment option for patients with refractory chronic cluster headache (CCH). Due to the small number of afflicted individuals, the knowledge about this specific therapy is limited. In this study, we present our experiences with bilateral occipital nerve stimulation (ONS) in patients with CCH focusing on patient selection, pre- and postoperative evaluation, surgical procedures, and outcome. PATIENTS AND METHODS: Since December 2008, 10 patients with CCH have been treated with ONS at our department. Patients were recruited and clinically followed by a neurologist and a neurosurgeon. Baseline data records on frequency, intensity, and duration of attacks as well as the use of medication were assessed with a 30-day diary. Standardized questionnaires were used pre- and postoperatively and during the follow-up on a regular basis. Surgical procedure and stimulation parameters were standardized for all patients. Lead implantation was followed by a test period of 30 days prior to implantation of the permanent generator. Mean follow-up time was 12 months (range 3-18). RESULTS: All patients responded to the stimulation treatment. Frequency, duration, and severity of the cluster attacks were reduced in 90% of the patients. One patient had a significant reduction of his concomitant tension headache. 70 % of the patients needed less medication during the attacks. All patients reported an improvement in their quality of life. The SF-36 showed a tendency toward objective improvement in the field of psychological comfort. As a major adverse event, one generator had to be exchanged due to a local infection. Another patient had to be reoperated due to a scar tissue formation around the thoracic connector. CONCLUSIONS: ONS is a valuable tool in the treatment of patients with refractory CCH. According to our data, the potential side effects and complication rates of the operation are small. With a meticulous selection of patients by an interdisciplinary team, CCH can bed improve in the majority of the patients. Yet, the optimal parameters for the stimulation regarding pulse width and frequency remain unclear. For this reason, we started a prospective single-center observational trial at our center in October 2009, including patients with ONS, to identify the best stimulation parameters.

[Bilateral occipital nerve stimulation for the treatment of chronic cluster headache: case series and initiation of a prospective study]. / Beidseitige Nervus-occipitalis-Stimulation zur Behandlung des therapierefraktären chronischen Cluster-Kopfschmerzes: eigene Fallserie und Initiierung einer prospektiven Studie.

BACKGROUND: The chronic cluster headache (CCH) is a disabling disorder for every patient. Treatment is a challenging situation for the physician. Some patients will not experience adequate resolution of their cluster attacks by medication and the prophylaxis does not reduce the attacks sufficiently. Therefore, other treatment options have to be found. METHODS: Since December 2008 seven patients with CCH have been treated by bilateral occipital nerve stimulation (ONS) at the University Hospital Essen. Implantation of the electrodes and stimulation paradigms were standardised. The maximum follow-up to date is 12 months. RESULTS: ONS was successfully employed in all patients. The intensity of the attacks decreased by 50 %. The consumption of attack medication was reduced by 77 % on average. Some patients could reduce their medication prophylaxis. A tendency towards improved quality of life was seen in all patients by means of a standardised questionnaire (SF-36). One generator had to be exchanged due to infection. Scar formations required reoperation and adhesiolysis of the thoracic connector in another patient. 6 out of 7 patients would fully recommend the operation. CONCLUSION: Bilateral ONS is a promising treatment for CCH, with a low risk profile in our experience. Further studies have to be conducted to clarify the mechanism of the stimulation and optimal parameters of ONS. For this particular reason, patients with CCH have been included in a prospective study since October 2009.

Effective long-term subthalamic stimulation in PARK8 positive Parkinson's disease.

Whether patients with genetically defined Parkinson's disease (PD) may be particularly eligible to benefit from deep brain stimulation of the nucleus subthalamicus (STN-DBS) is currently the subject of debate. We report on a patient with advanced PD due to R793M missense mutation in the LRRK2 gene successfully treated by STN-DBS. Disease onset was at age 42 with bradykinesia, rigidity and rest tremor. During the course of the disease he developed severe motor fluctuations, dyskinesias, postural instability with falls, but preserved levodopa responsiveness. At age 60 the patient was treated by bilateral DBS of the STN. At one year after surgery a 66% improvement of the UPDRS motor score in the off-medication state was determined. During the long-term follow-up there was sustained benefit with 56% improvement of motor score after 8 years. Our report adds evidence that patients with LRRK2 monogenetic Parkinsonism are well suited candidates for DBS treatment and may indicate a potential genetic predictor for positive long-term effect of STN-DBS treatment.

Effective thalamic deep brain stimulation for neuropathic tremor in a patient with severe demyelinating neuropathy.

Postural and action tremor in peripheral neuropathy is characteristic of Roussy-Levy syndrome. A patient with a severe demyelinating neuropathy and disabling neuropathic tremor successfully treated by deep brain stimulation (DBS) is reported. Disease onset was at age 63 years with sensory symptoms and slight action tremor. Within the following 9 years a severe, drug resistant, postural and action tremor developed rendering the patient unable to feed himself. At age 72 years the patient was treated by bilateral DBS of the ventral intermediate thalamic nucleus, with a useful 30% reduction in tremor. The clinical benefit of the stimulation remained stable over a 1 year postoperative observation period.

Failure properties of intraluminal thrombus in abdominal aortic aneurysm under static and pulsating mechanical loads.

OBJECTIVES: It has been suggested that mechanical failure of intraluminal thrombus (ILT) could play a key role in the rupture of abdominal aortic aneurysms (AAAs), and in the present study, this hypothesis has been investigated. An in vitro experimental approach has been proposed, which provides layer-specific failure data of ILT tissue under static and pulsatile mechanical loads. METHODS: In total, 112 bone-shaped test specimens are prepared from luminal, medial, and abluminal layers of eight ILTs harvested during open elective AAA repair. Three different types of mechanical experiments, denoted as control test, ultimate strength test, and fatigue test were performed in Dulbecco's modified eagle's medium (DMEM) supplemented with fetal calf serum, L-ascorbic acid, and antibiotics at 37 degrees C and pH 7.0. In detail, fatigue tests, which are experiments, where the ILT tissue is loaded in pulsatile manner, were carried out at three different load levels with a natural frequency of 1.0 Hz. RESULTS: ILT's ultimate strength (156.5 kPa, 92.0 kPa, and 47.7 kPa for luminal, medial, and abluminal layers, respectively) and referential stiffness (62.88 kPa, 47.52 kPa, and 41.52 kPa, for luminal, medial, and abluminal layers, respectively) continuously decrease from the inside to the outside. ILT tissue failed within less than 1 hour under pulsatile loading at a load level of 60% ultimate strength, while a load level of about 40% ultimate strength did not cause failure within 13.9 hours. CONCLUSIONS: ILT tissue is vulnerable against fatigue failure and shows significant decreasing strength with respect to the number of load cycles. Hence, after a reasonable time of pulsating loading ILT's strength is far below its ultimate strength, and when compared with stress predictions from finite element (FE) studies, this indicates the likelihood of fatigue failure in vivo. Failure within the ILT could propagate towards the weakened vessel wall behind it and could initialize AAA failure thereafter.

Creatine supplementation in Parkinson disease: a placebo-controlled randomized pilot trial.

Mitochondrial dysfunction plays a major role in the pathogenesis of Parkinson disease (PD). Creatine (Cr) is an ergogenic compound that exerts neuroprotective effects in animal models of PD. We conducted a 2-year placebo-controlled randomized clinical trial on the effect of Cr in 60 patients with PD. Cr improved patient mood and led to a smaller dose increase of dopaminergic therapy but had no effect on overall Unified Parkinson's Disease Rating Scale scores or dopamine transporter SPECT.

Refinement of the PARK3 locus on chromosome 2p13 and the analysis of 14 candidate genes.

Parkinson's disease (PD) is a common neurodegenerative disorder with clinical features of bradykinesia, rigidity, resting tremor and postural instability resulting from the deficiency of dopamine in the nigrostriatal system. Previously we mapped a susceptibility gene for an autosomal dominant form of PD to a 10.6 cM region of chromosome 2p (PARK3; OMIM 602404). A common haplotype shared by two North American kindreds (Families B and C) genealogically traced to Southern Denmark and Northern Germany suggested a founder effect. Here we report progress in the refinement of the PARK3 locus and sequence analysis of candidate genes within the region. Members of families B and C were genotyped using polymorphic markers, reducing the minimum common haplotype to eight markers spanning a physical distance of 2.5 Mb. Analysis of 14 genes within the region did not reveal any potentially pathogenic mutations segregating with the disease, implying that none of these genes are likely candidates for PARK3.

[A comparison of cholinesterase inhibitors and ginkgo extract in treatment of Alzheimer dementia]. / Ein Vergleich von Cholinesterasehemmern und Ginkgo-Extrakt in der Behandlung der Alzheimer-Demenz.

AIM: To compare the effectiveness of second-generation cholinesterase inhibitors (donepezil, rivastigmine, metrifonate) with that of the special ginkgo extract EGb 761R in Alzheimer's disease. METHOD: Analysis of the effect on cognition with the aid of the ADAS-cog.scale, placebo-adjusted, within six months; statistical evaluation of the effect using the confidence interval for the potential mean improvement. RESULTS: All medications are statistically significantly superior to placebo. The mean improvement is larger for the cholinesterase inhibitors than for the ginkgo extract. In the statistically unfavorable case, the effect of the cholinesterase inhibitors is still appreciable, but not for the ginkgo extract. CONCLUSION: Until the results of direct comparative studies are available, the present results indicate a superior effect of cholinesterase inhibitors over the ginkgo extract in the treatment of mild to moderate Alzheimer's disease.

Hormone therapy failure in human prostate cancer: analysis by complementary DNA and tissue microarrays.

BACKGROUND: The molecular mechanisms underlying the progression of prostate cancer during hormonal therapy have remained poorly understood. In this study, we developed a new strategy for the identification of differentially expressed genes in hormone-refractory human prostate cancer by use of a combination of complementary DNA (cDNA) and tissue microarray technologies. METHODS: Differences in gene expression between hormone-refractory CWR22R prostate cancer xenografts (human prostate cancer transplanted into nude mice) and a xenograft of the parental, hormone-sensitive CWR22 strain were analyzed by use of cDNA microarray technology. To validate the data from cDNA microarrays on clinical prostate cancer specimens, a tissue microarray of specimens from 26 prostates with benign prostatic hyperplasia, 208 primary prostate cancers, and 30 hormone-refractory local recurrences was constructed and used for immunohistochemical detection of protein expression. RESULTS: Among 5184 genes surveyed with cDNA microarray technology, expression of 37 (0.7%) was increased more than twofold in the hormone-refractory CWR22R xenografts compared with the CWR22 xenograft; expression of 135 (2.6%) genes was reduced by more than 50%. The genes encoding insulin-like growth factor-binding protein 2 (IGFBP2) and 27-kd heat-shock protein (HSP27) were among the most consistently overexpressed genes in the CWR22R tumors. Immunohistochemical analysis of tissue microarrays demonstrated high expression of IGFBP2 protein in 100% of the hormone-refractory clinical tumors, in 36% of the primary tumors, and in 0% of the benign prostatic specimens (two-sided P =.0001). Overexpression of HSP27 protein was demonstrated in 31% of the hormone-refractory tumors, in 5% of the primary tumors, and in 0% of the benign prostatic specimens (two-sided P =.0001). CONCLUSIONS: The combination of cDNA and tissue microarray technologies enables rapid identification of genes associated with progression of prostate cancer to the hormone-refractory state and may facilitate analysis of the role of the encoded gene products in the pathogenesis of human prostate cancer.

[Transurethral thermotherapy of the prostate--a very promising treatment method for benign prostatic hyperplasia]. / Transurethrale Thermotherapie der Prostata (TUMT)--Eine vielversprechende Behandlungsmethode der benignen Prostatahyperplasie.

Transurethral resection of the prostate remains the most common method for the treatment of benign prostatic hyperplasia (BPH). Due to unsatisfactory results in about 18% of the patients new methods to treat BPH have been developed. We evaluated 45 patients 6 and 12 months after transurethral microwave thermotherapy using the Prostatron device with Prostasoft 2.5 software. There was a significant improvement of the urinary symptoms and of the quality of life index from 18 to 9.5 and from 3.2 to 1.6 points, respectively. Urinary flow rate improved from 8.8 to 12.1 ml/sec and residual urine was reduced from 101 to 52 ml. The treatment was well tolerated and side effects were minimal. High-energy transurethral microwave thermotherapy is an effective and safe minimal invasive alternative to treat BPH in selected patients. As no anesthesia is required transurethral microwave thermotherapy can also be offered to high risk and elderly patients.

Epidemiological, genetic, pharmacological, kinesiological, nuclear medical (IBZM-SPECT), standard and functional MRI studies on Parkinson's disease and related disorders and economic evaluation of Parkinson's disease therapy--clinical projects in the BMFT-research program Munich: "Parkinson's disease and other basal ganglia disorders".

The results of selected clinical research projects related to epidemiological, genetic, pharmacological, kinesiological, and neuroimaging aspects (SPECT, PET, MRI, functional MRI) of basal ganglia disorders such as Parkinson's disease, Progressive Supranuclear Palsy, Multiple System Atrophy and Wilson's disease are summarized. A retrospective pharmacoeconomic analysis of Parkinson's disease is presented. These studies are part of a nationwide research program of the German ministry of research and technology (BMFT) entitled "Parkinson's disease and other basal ganglia disorders" and were carried out at the Department of Neurology, LMU München.

Timing, dosing and duration of antimicrobial prophylaxis in urology: a study in guinea pigs with special reference to high-risk conditions.

A study in guinea pigs was performed to investigate the importance of timing, dosage and duration of antimicrobial prophylaxis in urologic surgery. To simulate high-risk conditions, in one group a foreign body was implanted subcutaneously. The prostate and one kidney were cauterized and bacteremia was induced by intravenous injection of an Escherichia coli suspension. Various ciprofloxacin regimens were tested. The results indicate that antimicrobial prophylaxis is beneficial only if administered before or shortly after surgery. Full therapeutic dosage may not be necessary for prophylactic efficacy. Single-dose prophylaxis was as effective as multiple doses. Foreign body infection could be prevented by single-dose prophylaxis.

MICs of ciprofloxacin and trimethoprim for Escherichia coli: influence of pH, inoculum size and various body fluids.

The influence of pH, inoculum size, human urine and prostatic extract on the MICs of ciprofloxacin and trimethoprim for Escherichia coli was investigated. There was no influence by the bacterial inoculum size within wide ranges on either drug. An increase in pH had a variable influence on the MICs of trimethoprim for E. coli but lowered those of ciprofloxacin considerably. Human prostatic extract increased the trimethoprim MIC for E. coli but lowered those of ciprofloxacin as compared to Mueller Hinton broth. Human urine increased the MICs of both drugs for E. coli.

Transurethral incisions of the prostate under local anaesthesia in high-risk patients: a pilot study.

Transurethral incision of the prostate under local anaesthesia was performed in 27 patients with symptoms of infravesical obstruction and an estimated prostatic weight of 20 g or less. Local anaesthesia (lidocaine 1%) was infiltrated transurethrally under the urethral prostatic mucosa using a special needle adaptable to the resectoscope. Pain control, assessed with a scoring system, was judged as good or very good by the majority of patients (25) and fair by the remaining 2 patients. No patient required conversion to another type of anaesthesia. The results of surgery as estimated by symptom score, uroflowmetry, and patients' personal evaluation were good. Transurethral incision of the prostate can be satisfactorily performed under local anaesthesia; this may be especially applicable to high-risk surgical patients. Incision of the prostate in the treatment of benign prostatic hyperplasia may be performed as an outpatient procedure in selected cases.