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.

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.

[Check-up-examinations in internal medicine]. / Der internistische Check-up.

A growing body of evidence supports or rejects preventive interventions in asymptomatic adults. Thus, counseling for smoking cessation and some immunizations have been shown to be cost-effective. Evidence supports screening for body weight (obesity), hypertension, hyperlipidemia, cervical cancer, colorectal cancer and breast cancer. Screening for lung, pancreatic and ovarian cancer has no effect on outcome and should not be performed. Controversial preventive interventions include general screening for diabetes mellitus in the young adult, thyroid disorders and prostate cancer. Physicians should be aware of a possible hidden agenda in patients presenting for a check-up.

Value of gonadotropin-releasing hormone testing in the differential diagnosis of androgen deficiency in elderly men.

Elderly men with low testosterone (T) levels are increasingly diagnosed to have partial androgen deficiency of the aging male (PADAM). Frequently, magnetic resonance imaging is performed to exclude pituitary adenoma. The value of GnRH testing to differentiate PADAM from secondary hypogonadism is unknown. Serum levels of T as well as LH and FSH at baseline and after GnRH were evaluated in the following groups: 1) 24 elderly men with low serum T (<11.7 nmol/liter), 2) 25 elderly men with normal serum T levels (>11.7 nmol/liter), 3) 10 men with primary hypogonadism, 4) 24 men with secondary hypogonadism, and 5) 13 healthy young volunteers. In elderly men, T levels were lower (P < 0.001) and gonadotropin levels higher (P = 0.03) compared with younger controls. LH and FSH response to GnRH was higher in elderly men with low T levels (PADAM) compared with elderly men with normal T levels (P = 0.02 and P < 0.001) in the presence of similar basal gonadotropin levels. To differentiate secondary hypogonadism from PADAM with a sensitivity of 100%, a T less than 10 nmol/liter had a specificity of 50%. This specificity was improved to 75% by using a cutoff of less than or equal to 15 mU/liter increase of LH upon GnRH stimulation. Overall, decreased T levels and increased LH levels in elderly men suggest a primary Leydig cell dysfunction. In the subgroup of elderly men with low T levels, an increased LH response to GnRH with normal basal LH levels suggests additional, possibly hypothalamic changes. To exclude secondary hypogonadism in PADAM, diagnostic accuracy can be improved by using GnRH testing.

Risk factor control and perceptions of risk factors in patients with coronary heart disease.

Treatment of hypertension and hyperlipidaemia improves cardiovascular and overall mortality in patients with coronary heart disease. Adequate awareness of atherogenic risk factors is a key first step that enables patients to address their risk factors. In a recently completed study in coronary heart disease patients at coronary angiography and 18 months later, we found that skewed views about atherogenic risk factors in general were expressed. In addition, awareness of the patients' own hypercholesterolaemia or diabetes mellitus was often inadequate or lacking, in contrast to their awareness of blood pressure or bad smoking habits. Awareness of risk factors had only marginally improved 18 months after the initial investigation. Smoking habits, total cholesterol, and HDL values had improved over 18 months but lipid values were far from reaching target values of accepted guidelines. A majority of our patients remained with at least one treatable and insufficiently controlled atherogenic risk factor, usually hypercholesterolaemia. Interestingly, higher awareness of risk factors correlated with better risk factor control. These observations suggest that systematic interventions are necessary to further ameliorate secondary prevention in coronary heart disease. Successful standardized programmes of high or perhaps medium intensity, that include systematic screening of risk factors, reasoned educational interventions, and methodical management of treatable atherogenic risk factors according to accepted, guidelines, therefore require further attention in daily medical practice.