Role of somatostatins in gastroenteropancreatic neuroendocrine tumor development and therapy

The incidence and prevalence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have increased in the past 20 years. GEP-NETs are heterogeneous tumors, in terms of clinical and biological features, that originate from the pancreas or the intestinal tract. Some GEP-NETs grow very slowly, some grow rapidly and do not cause symptoms, and others cause hormone hypersecretion and associated symptoms. Most GEP-NETs overexpress receptors for somatostatins. Somatostatins inhibit the release of many hormones and other secretory proteins; their effects are mediated by G protein-coupled receptors that are expressed in a tissue-specific manner. Most GEP-NETs overexpress the somatostatin receptor SSTR2; somatostatin analogues are the best therapeutic option for functional neuroendocrine tumors because they reduce hormone-related symptoms and also have antitumor effects. Long-acting formulations of somatostatin analogues stabilize tumor growth over long periods. The development of radioactive analogues for imaging and peptide receptor radiotherapy has improved the management of GEP-NETs. Peptide receptor radiotherapy has significant antitumor effects, increasing overall survival times of patients with tumors that express a high density of SSTRs, particularly SSTR2 and SSTR5. The multi-receptor somatostatin analogue SOM230 (pasireotide) and chimeric molecules that bind SSTR2 and the dopamine receptor D2 are also being developed to treat patients with GEP-NETs. Combinations of radioactive labeled and unlabeled somatostatin analogues and therapeutics that inhibit other signaling pathways, such as mammalian target of rapamycin (mTOR) and vascular endothelial growth factor, might be the most effective therapeutics for GEP-NETs.

[Diagnosis and therapy of hyperthyreosis]

Hyperthyreosis, diabetes and calcium disorders are frequent endocrine diseases that are often encountered by the primary care physician. The diagnosis of hyperthyreosis can be established by many different laboratory and analytical tests. However, the clinical context can often guide a specific diagnostic approach. Graves disease and toxic adenomas are the most frequent causes of hyperthyreosis. Diagnosis of Graves disease is most frequent between age 35 and 60 and about 10-20% of patients show already initially signs of endocrine orbithopathy. Measurement of thyroid stimulating immunoglobulins (TSI) is especially valuable in unclear cases. Toxic adenomas are always diagnosed by thyroid uptake studies. Rare causes of hyperthyreosis include thyreoiditis, which is characterized by transient hyperthyreosis (<2 months), and thyrotoxicosis factitia. Here, we discuss diagnosis and therapy of different causes of hyperthyreosis based on three clinical examples.

[Prophylaxis and therapy of postdural puncture headache--a critical evaluation of treatment options]

Since the first description of spinal and epidural anaesthesia, postdural puncture headache (PDPH) is a well known complication. Its prophylaxis and treatment has been studied and discussed for more than 100 years, but the evidence is still limited. Due to relatively low prevalence of PDPH, prospective RCTs are often missing, and the frequently self-limiting character of PDPH impedes an adequate interpretation of results from studies without a control group. Taking side effects and complications into account, a prophylactic treatment of PDPH cannot be recommended. In case of PDPH, non-opioid analgesics are the first choice treatment. The epidural blood patch remains the mainstay of severe PDPH therapy. Noninvasive therapies like theophylline, sumatriptan and ACTH can be an alternative. However, an evidence-based recommendation is lacking. The development of standard operating procedures for accidental dural punctures and PDPH is recommended.

Use of human embryonic stem cells and umbilical cord blood stem cells for research and therapy: a prospective survey among health care professionals and patients in Switzerland

BACKGROUND: Scientific progress in the biology of hematopoietic stem cells (HSCs) provides opportunities for advances in therapy for different diseases. While stem cell sources such as umbilical cord blood (UCB) are unproblematic, other sources such as human embryonic stem cells (hESCs) raise ethical concerns. STUDY DESIGN AND METHODS: In a prospective survey we established the ethical acceptability of collection, research, and therapy with UCB HSCs versus hESCs among health care professionals, pregnant women, patients undergoing in vitro fertilization therapy, parents, and HSC donors and recipients in Switzerland. RESULTS: There was overall agreement about an ethical justification for the collection of UCB for research and therapy in the majority of participants (82%). In contrast, research and therapy with hESCs was acceptable only by a minority (38% of all responders). The collection of hESCs solely created for HSC collection purposes met overall with the lowest approval rates. Hematologists displayed among the participants the highest acceptance rates for the use of hESCs with 55% for collection, 63% for research, and 73% for therapy. CONCLUSIONS: This is the first study assessing the perception of hESCs for research and therapy in comparison with UCB HSCs in different target groups that are exposed directly, indirectly, or not at all to stem cell-based medicine. Our study shows that the debate over the legitimacy of embryo-destructive transplantation medicine is far from over as particularly hESC research continues to present an ethical problem to an overwhelming majority among laypersons and even among health care professionals.

Onychomycosis: The Current Approach to Diagnosis and Therapy, 2nd Edition

This new edition of a bestselling text illustrates the changes in attitudes towards fungal nail infections: previously attracting little interest, with a reputation for stubborn resistance to treatment, they have now reached the stage where there has been enormous recent scientific and medical progress, bringing with it a real possibility for a successful outcome of therapy for a growing population of patients. With this process has come the realization that there is now a clear choice of treatment determined by rational medical assessment. This book has been written by clinicians for clinicians, to provide a guide to the steps needed to identify and effectively manage the patient with onychomycosis. It is the first title in a new Series in Dermatological Therapy launched in conjunction with the Journal of Dermatological Therapy.

[Pancytopenia and hemolysis--diagnosis, differential diagnosis and therapy of pernicious anemia]

Pernicious anemia and Vitamin B12 deficiency have a wide range of symptoms and are a common finding in the elderly. A 73 year old female is admitted to the hospital because of dyspnea, fatigue and loss of appetite and weight. While previous medical history and physical examination are inconspicuous, laboratory findings show severe pancytopenia with macrocytosis, low reticulocyte count and marked signs of hemolysis. A very low serum level of vitamin B12 and chronic atrophic type A gastritis upon endoscopy with presence of parietal cell antibodies in the serum lead to the diagnosis of pernicious anemia. Complete restitution is achieved by parenteral vitamin B12 substitution. Nowadays, severe pernicious anemia is only rarely seen. The differential diagnosis of pancytopenia (with macrocytic anemia) combined with hemolysis and the essential hints to the diagnosis of pernicious anemia are discussed, and thereby practical aspects including therapy actualized.

[The nasopalatine duct cyst--epidemiology, diagnosis and therapy]

The nasopalatine duct cyst is the most frequent nonodontogenic cyst of the jaws. The cyst originates from epithelial remanents from the nasopalatine duct. The cells may be activated spontaneously during life, or are eventually stimulated by the irritating action of various agents (infection, etc.). Generally, patients present without clinical signs and symptoms. Therefore, the tentative diagnosis "nasopalatine duct cyst" is often based on a coincidental radiological finding on a routine panoramic view or occlusal radiograph. The definite diagnosis should be based on clinical, radiological and histopathologic findings. The therapy of nasopalatine duct cysts consists of an enucleation of the cystic tissue, only in rare cases a marsupialization needs to be performed. The present review of the literature presents and discusses the epidemiology, etiology, diagnostic work-up, differential diagnostic aspects, histopatholgy, and therapeutic strategies for nasopalatine duct cysts.

[Systematic aspects and therapy of diabetic neuropathy]

Diabetic neuropathy (DN) is an important complication contributing to high morbidity and morbidity of diabetic subjects. Primarily, interventional strategies aim at normalization hyperglycemia (to prevent development and progression of DN), at early diagnosis and at prevention of ulcers and amputations. In addition, an increasing number of pharmaceutical agents is used to symptomatically treat dysesthesia and pain associated with DN. During recent years attempts have been made to pharmacologically treat DN by acting on underlying patho-physiological mechanisms (e.g. sorbitol pathway, non-enzymatic glycation, microvascular abnormalities). So far, these strategies have not changed clinical praxis. This review will give a systematic overview of DN and summarize current pharmacological options to symptomatically treat dysesthesia and pain associated with DN.

[Diagnosis and therapy of depression in the heart disease patient]

Even though depressions and depressive symptoms are frequently observed in patients with medical diseases, their psychological problems are often neither diagnosed nor treated. Diagnosis of mood state might be easy in isolated cases yet it often is not since the precise nature of normal mood cannot be expressed in quantitative terms. Furthermore, depression can only be diagnosed based on the doctor's clinical appraisal and the patient's own description of his/her complaints. There is no gold standard on which depressive symptoms can be based on--and further on, depression is not a diagnosis. Instead, it is a syndrome that calls for differential diagnoses before treatment can be offered. Diagnosing depressive comorbidity in patients with medical complaints is even more difficult because of the overlap between symptoms of depression and accompanying symptoms of the somatic illness e.g. lack of energy. Although depressive states have been known to be a risk factor for the prognosis of patients with coronary heart disease for a long time, there is a paucity of research about the therapy these patients undergo due to the fact that tricyclic anti-depressants can have cardiotoxic effects on patients with heart disease. The treatment of depression in these patients has become a much lower risk since the introduction of serotonin reuptake inhibitors. There is widespread evidence that depressive comorbidity has a negative impact on the prognosis of medical disorders. Despite the complex nature of diagnosing depression, proper diagnosis and treatment is increasingly important in internal medicine and especially cardiology.

[Systemic ANCA-associated vasculitis--diagnosis and therapy]

ANCA-associated vasculitis represents a group of small-vessel vasculitides, including Wegener's granulomatosis, microscopic polyangiitis and the Churg-Strauss-syndrome. These diseases affect mainly small arteries, venules and capillaries, showing a lack of immunocomplex formation on immunohistology, the so-called "pauci-immune" vasculitis. Nevertheless, Anti-Neutrophil Cytoplasmatic Autoantibodies (ANCA's) are pathogenic for this type of disease. In spite of important advances in technical diagnostic tools, careful medical history and clinical examinations often give the clues for the correct diagnosis. Recent collaborative therapeutic studies have lead to therapeutic schemas that are much more adapted to the individual disease state. Besides the acute and sometimes life-threatening form of ANCA-vasculitis, chronic disease and relapses become more important in clinical practice. Thus, therapeutic efficacy must be outweighed against long-term toxicity to make the right choice for therapeutic intervention in ANCA-associated vasculitis.