Pyridostigmine bromide versus fludrocortisone in the treatment of orthostatic hypotension in Parkinson's disease - a randomized controlled trial.

BACKGROUND AND PURPOSE: Evidence for effective treatment options for orthostatic hypotension (OH) in Parkinson's disease (PD) is scarce. Elevation of cholinergic tone with pyridostigmine bromide has been reported as a way to improve blood pressure (bp) regulation in neurogenic hypotension without causing supine hypertension. METHODS: This was a double-centre, double-blind, randomized, active-control, crossover, phase II non-inferiority trial of pyridostigmine bromide for OH in PD (clinicaltrials.gov NCT01993680). Patients with confirmed OH were randomized to 14 days 3 × 60 mg/day pyridostigmine bromide or 1 × 0.2 mg/day fludrocortisone before crossover. Outcome was measured by peripheral and central bp monitoring during the Schellong manoeuvre and questionnaires. RESULTS: Thirteen participants were enrolled between April 2013 and April 2015 with nine participants completing each trial arm. Repeated measures comparison showed a significant 37% improvement with fludrocortisone for the primary outcome diastolic bp drop on orthostatic challenge (baseline 22.9 ± 13.6 vs. pyridostigmine bromide 22.1 ± 17.0 vs. fludrocortisone 14.0 ± 12.6 mmHg; P = 0.04), whilst pyridostigmine bromide had no effect. Fludrocortisone caused an 11% peripheral systolic supine bp rise (baseline 128.4 ± 12.8 vs. pyridostigmine bromide 130.4 ± 18.3 vs. fludrocortisone 143.2 ± 10.1 mmHg; P = 0.01) but no central mean arterial supine bp rise (baseline 107.2 ± 7.8 vs. pyridostigmine bromide 97.0 ± 12.0 vs. fludrocortisone 107.3 ± 6.3 mmHg; P = 0.047). Subjective OH severity, motor score and quality of life remained unchanged by both study interventions. CONCLUSIONS: Pyridostigmine bromide is inferior to fludrocortisone in the treatment of OH in PD. This trial provides first objective evidence of the efficacy of 0.2 mg/day fludrocortisone for OH in PD, causing minor peripheral but no central supine hypertension. In addition to peripheral bp, future trials should include central bp measurements, known to correlate more closely with cardiovascular risk.

Alterations in vascular function in primary aldosteronism: a cardiovascular magnetic resonance imaging study.

Excess aldosterone is associated with increased cardiovascular risk. Aldosterone has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance imaging (CMR) allows study of vascular function by measuring aortic distensibility. We compared aortic distensibility in primary aldosteronism (PA), essential hypertension (EH) and normal controls and explored the relationship between aortic distensibility and pulse wave velocity (PWV). We studied PA (n=14) and EH (n=33) subjects and age-matched healthy controls (n=17) with CMR, including measurement of aortic distensibility, and measured PWV using applanation tonometry. At recruitment, PA and EH patients had similar blood pressure and left ventricular mass. Subjects with PA had significantly lower aortic distensibility and higher PWV compared with EH and healthy controls. These changes were independent of other factors associated with reduced aortic distensibility, including ageing. There was a significant relationship between increasing aortic stiffness and age in keeping with physical and vascular ageing. As expected, aortic distensibility and PWV were closely correlated. These results demonstrate that PA patients display increased arterial stiffness compared with EH, independent of vascular ageing. The implication is that aldosterone invokes functional impairment of arterial function. The long-term implications of arterial stiffening in aldosterone excess require further study.

Arabidopsis thaliana transgenics overexpressing IBR3 show enhanced susceptibility to the bacterium Pseudomonas syringae.

The gene, indole-3-butyric acid (IBA)-RESPONSE (IBR) 3, is thought to participate in peroxisomal ß-oxidation of IBA to indole-3-acetic acid. Here we show that IBR3 may also play a role in Arabidopsis thaliana defence response to microbial pathogens. IBR3 is up-regulated during infection by virulent Pseudomonas syringae pv. tomato (Pst) DC3000 bacteria. Although mutant ibr3-4 did not show a pathogen phenotype, lines overexpressing IBR3 demonstrated enhanced susceptibility to Pst DC3000. Increased susceptibility phenotypes of IBR3 overexpressors were correlated with defective SA defence signalling and impairment of pattern-triggered immunity (PTI) activation. Notably, reactive oxygen species production was reduced in IBR3 overexpressors after treatment with the microbe-associated molecular patterns flg22 and efl26. Later PTI responses, such as accumulation of FRK1 transcripts and callose deposition were also reduced in transgenics overexpressing IBR3 after inoculation with the Type III secretion system deficient bacterial mutant Pst DC3000 hrcC or treatment with flg22 or elf26. Importantly, overexpression of IBR3 did not affect indole-3-acetic acid content or auxin-responsive gene expression. These results suggest a novel role for IBR3 in A. thaliana defence response against bacterial pathogens.

[Pain in multimorbid internistic patients]. / Schmerzen bei multimorbiden internistischen Patienten.

Pain and pain management in multimorbid patients is a subject which is mostly unknown. General rules in pain management like the WHO analgesic ladder and its recommendations are to be equally respected as with other patients. As multimorbidity is a common problem especially in the elderly population, some changes in physiology, pharmacodynamics and pharmacokinetics have to be taken into consideration. A careful and slow adoption of dosage leads to more safety and tolerability. Other main problems of multimorbidity are drug-drug, drug-disease or disease-disease interactions, which influence the choice of analgesic medication. As especially the number of drug-drug interactions is endless, available software is a valuable aid to become aware of interactions and help weight the compromises.

[Identification and clinical use of the Metabolic Syndrome]. / Wird das Metabolische Syndrom in der Klinik erkannt und die Diagnose aktiv verwendet?

The Metabolic Syndrome is characterised by the following components: atherogenic dyslipidemia, elevated blood pressure, elevated glucose and abdominal obesity. 22% of 415 patients of an outpatient clinic in internal medicine fulfilled the criteria of a Metabolic Syndrome. The most common components were abdominal obesity, elevated blood pressure and elevated triglyceride. Only one in five treating physicians diagnosed a Metabolic Syndrome. Our data show that the concept of the Metabolic Syndrome has limited utility in clinical practice.

Clinical proteomics: current techniques and potential applications in the elderly.

In Western societies the process of aging is closely related to the onset of chronic diseases, such as coronary artery disease, diabetic nephropathy or different types of malignancies. Novel biomarkers are urgently needed to assist in managing these diseases. Parallel to technical advancements possibilities for the analysis of the human proteome for biomarkers have recently made considerable progress. In a first part, this article attempts to describe the main proteomic platform technologies, their advantages and disadvantages and will critically review proteomic study design aspects necessary to obtain valuable data, such as choosing suitable clinical specimens, data processing and mining. Physiological age-related alterations in the human proteome have been described and were similar to indolent changes associated with chronic diseases, in particular of the kidneys. Therefore, in a second part this review will introduce several examples for the application of clinical proteomics to aging itself and age-related diseases. Several recent proteome studies with clinically sound designs are available. These performed careful validation in blinded cohorts. It is anticipated that a boost in disease-related proteomic data is expected in the very near future. However, lessons of the past teach the strict adherence to proper technological approaches, appropriate statistics, and large databases to fulfil these high expectations.

Angiogenesis and hypertension: an update.

The purpose of this review is to provide a basic understanding of the important relationship between microvascular remodelling, angiogenesis and hypertension, that is, provide an overview of recent experimental and clinical evidence from anti-hypertensive and pro- and anti-angiogenic therapy with respect to hypertension and microvascular structure. Microvascular rarefaction, that is, a loss of terminal arterioles and capillaries, is found in most forms of human and experimental arterial hypertension. This further increases peripheral resistance, and aggravates hypertension and hypertension-induced target organ damage. In some cases with a genetic predisposition, hypertension is preceded by a loss of microvessels. Therefore, new therapies aimed at reversing microvascular rarefaction potentially represent candidate treatments of hypertension. The microvasculature is formed by the continuous balance between de novo angiogenesis and microvascular regression. Imbalanced angiogenesis, in addition to functional shut-off of blood flow, contributes to microvascular rarefaction. Numerous clinical trials assessing anti-angiogenic agents in cancer patients show that this therapy leads to microvascular rarefaction and causes or aggravates hypertension. The development of specific pro-angiogenic treatment to correct hypertension or ischaemic disorders, however, it is still in its infancy. On the other hand, long-term treatment by classic anti-hypertensive therapies that present vasodilator activity can correct for hypertension-associated rarefaction in man.

Determination of effective tip geometries in Kelvin probe force microscopy on thin insulating films on metals.

In scanning probe techniques, accurate height measurements on heterogeneous surfaces are a major requirement. Different electrostatic potentials of various materials have a significant influence on the measured force/current and therefore a direct influence on the tip-sample distance. Kelvin probe force microscopy (KPFM) is based on a dynamic compensation of the electrostatic force while performing non-contact atomic force microscopy measurements. Thus, the influence of the electrostatic potentials can be minimized and accurate height measurements become possible. Here, the study of ultra-thin alkali halide films on Cu(111) investigated by KPFM is presented. This work is focused on the interface between areas of bare Cu(111) and the first layers of salt. The compensation of the electrostatic potential allow us to determine layer heights with high accuracy. The second objective was to elaborate on the characterization of tip geometries across suitable nanostructures. Simulations of measured images are performed with different input parameters, which gives a direct estimation of the effective tip radius and geometry used for the measurements.

Proteomics in gerontology: current applications and future aspects--a mini-review.

BACKGROUND: Aging is closely related to the onset of chronic diseases, such as coronary artery disease, diabetic nephropathy or different types of malignancies, reflecting the demand for novel biomarkers to manage theses diseases. OBJECTIVE: The analysis of the human proteome for biomarkers has made considerable advances in the last years. METHODS: We describe the main technological approaches taken, their advantages and disadvantages. RESULTS: We will review the different clinical sources of material and attempt to highlight the different challenges and approaches associated with these. Age-related changes in the proteome have been described and were found to be highly similar to changes associated with chronic diseases. We will give several examples on the successful application of proteomics in the diagnosis, prognosis and therapy of these chronic diseases. CONCLUSIONS: A boost in disease-related proteomic information is expected in the very near future, and will also result in its broad clinical application. However, this view appears to be dependent on the strict adherence to proper technological/analytical parameters, correct statistics, and large databases that allow comparison of datasets provided by different scientists. Clearly, the proteome is by far too complex to be tackled by one laboratory on its own.

[Non-controllable blood pressure peaks--pheochromocytoma?]. / Nicht kontrollierbare Blutdruckspitzen--Phäochromozytom?

A 59-year old patient presented with a history of arterial hypertension, refractory to combined antihypertensive treatment with ACE-inhibitors, diuretics, calcium channel blockers and beta blockers. Blood pressure values ranged from 180/100mmHg to 90mmHg systolic after medication intake. Diagnostic work-up revealed renal artery stenosis on duplexsonography that was treated by percutaneous transluminal angioplasty and stent implantation. After the intervention, blood pressure values remained normal even without antihypertensive treatment.

[Diffuse abdominal pain and eosinophilia]. / Diffuse Bauchschmerzen und Eosinophilie.

Eosinophilic gastroenteritis is a rare clinical condition of unknown aetiology and heterogenic etiopathology. Important differential diagnoses are intestinal parasitic infections, hypereosinophilic syndrome, malignancies such as lymphoma and allergic diseases. The diagnosis can be made in most cases by patient history, routine laboratory testing and endoscopic biopsies or paracentesis. Patients with only mild diarrhea can be treated with antidiarrheal medications. More symptomatic patients are usually treated with corticosteroids.

[Premature coronary disease]. / Vorzeitige koronare Herzkrankheit.

The family history in a sportive 49 year old patient with coronary artery disease reveals several members with cardiovascular events. The diagnosis of dyslipidemia could be made in all the patient's children. Genetic analysis of the patient shows a heterozygous mutation of the apolipoprotein B-100 genotype. An accurate family history and screening for cardiovascular risk factors are mandatory in all patients with a history of premature coronary artery disease.

[Hypertension and hyperhidrosis. Pheochromocytoma]. / Hypertonie und Schwitzen. Phaochromozytom.

A 39-year-old woman was referred to our hypertension clinic with refractory hypertension. The patient history gave certain clues for pheochromocytoma. The diagnosis was proven with elevated metanephrines and computer tomography. The tumor was surgically removed.

[Chronic fatigue. IV--Assessment of a 40-year-old patient]. / Chronische Müdigkeit. IV-Abklärung eines 40-jährigen Exploranden.

A forty year old patient was referred by the federal insurance for medical assessment. His presenting complaint was chronic fatigue. The patient had been an intravenous drug user for years and had been infected with hepatitis C. He was treated with interferon. The patient history showed that he also suffered from anaemia and depression. He participated in a methadone substitution program. Our diagnostic procedures showed that he also has Hashimoto's thyroiditis.

[Schnitzler's syndrome with urticaria vasculitis]. / Schnitzler-Syndrom mit Urtikaria-Vaskulitis.

Schnitzler's syndrome is a rare disease characterized by the association of chronic urticaria, intermittent fever, bone pain, arthritis, and monoclonal IgM gammopathy. It was first described by the French dermatologist Liliane Schnitzler in 1974. Because of the variety of clinical signs, the syndrome is of concern to doctors of different specialties and is of special interest to internists, rheumatologists, hematologists and dermatologists. Up to now, treatment was often difficult and disappointing. Interleukin-1 receptor antagonists offer a new therapeutic option.

[Muscle pain. De Quervain throiditis]. / Muskelschmerzen. Thyreoiditis de Quervain.

A 62-year-old female patient presents with myalgia, dysphagia and daytime fatigue. Clinical examination is normal. Laboratory results show a hyperthyroidism and an increased erythrocyte sedimentation rate. Clinical presentation, an ultrasound and further examinations suggest a thyroiditis de Quervain. A treatment with NSAR is started. After eight weeks the thyroid hormones return to normal and the patient is asymptomatic.

[Orthostatic hypotension and hypertension lying down: a clinical dilemma. 56-year-old patient with multiple system atrophy]. / Orthostatische Hypotonie und Hypertonie im Liegen: Ein klinisches Dilemma. 56-jähriger Patient mit Multisystematrophie.

A 56-year-old patient with multisystem atrophy of Parkinson type presents himself with severe, symptomatic and orthostatic hypotension and concomitant arterial hypertension while in a recumbent position. Etiology and pathophysiology of orthostatic hypotension and concomitant hypertension in recumbent position is discussed as it relates to this specific patient. Specific indications for antihypertensive therapies and other potential therapeutic options are also discussed.