Cytoprotective effects of amifostine in the treatment of tumors

An efficient therapy of patients with tumorous diseases should include maximum killing of malignant cells with minimal damage to cells in healthy tissues. Radiotherapy and chemotherapy are frequently associated with a series of undesirable effects. Side effects related to the therapy may unfavorably influence quality of life for a short or long period of time, may cause the need to decrease the dosage or shorten the overall period of treatment or survival of the patient. Therefore, particular attention has recently been paid to compounds, which mitigate or eliminate the undesirable effects of the therapy. A way to decrease toxicity is the administration of radioprotective or chemoprotective compounds. The cytoprotection of healthy tissues by compounds from the aminothiol group is one of the most promising directions of research and clinical practice. Amifostin protects healthy tissue from damage induced by radio- or chemotherapy. In comparison with patients treated by radiotherapy only, radiotherapy supplemented with amifostin proved to cause significantly less acute and late untoward effects of therapy. The paper describes the possibilities of using radioprotective drugs, especially amifostin, in the therapy of tumors with particular emphasis to the needs of physicians dealing with the problems of internal medicine.     

Hypothyroidism and heart failure

Effects of thyroid gland hormones on cardiovascular system have been known for many years. Thyroid gland hormones deficiency is connected with a range of metabolic and hemodynamic changes which can contribute to a genesis of heart failure. Recent works refer to an importance of connection of thyroid gland hormones metabolism with heart insufficiency pathophysiology. That is especially a syndrome of a low trijodthyronin level marked as euthyroid sick syndrome which is significantly more frequent in patients with chronic heart failure compared to a population of healthy individuals. Recent clinical works proved that treatment administration of thyroid gland hormones to patients with heart failure is connected with favourable hemodynamic changes and increased working capacity if the treatment is well tolerated.     

Budd-Chiari syndrome--hematologists' part in the multidisciplinary approach

Budd-Chiari syndrome presents a serious disease with a complex etiology and clinical manifestations, which is associated with high morbidity and mortality. An early diagnosis and therapy is mandatory due to the severity of disease and therapy contains the treatment of underlying disorder, anticoagulation therapy and therapy of liver impairment. We discuss hematologists' contribution to the diagnostic approach and therapy of this syndrome.     

Headache and Liver Disease: Is Their Relationship More Apparent Than Real?

Headache is regarded by patients as a disturbing (or unpleasant) symptom. It can be produced by either organic diseases or functional head abnormalities. Twenty-five years ago headache was supposed to be a psychosomatic angiospastic algia. Certain unusual forms were thought to be caused by triggers like anger, cough, exertion, and sexual activity. Experimental research explored the role of circulating serotonin, prostaglandin, estrogen levels, and platelet abnormalities. As computed tomography, helical computed tomography, and scanning or magnetic resonance imaging evolved, new data became available. None of the newer reports have demonstrated liver involvement as a cause of headache. This minireview intends to cover the spectrum of brain alteration in liver disease. It describes some of the pathophysiological characteristics of hepatic encephalopathy and, also, the relationship among migraine, constipation, and liver disease.     

Telomerase as a diagnostic and predictive marker in colorectal carcinoma

In a search for molecular markers providing both informative diagnostics of malignant disease, and rational stratification of a therapeutic strategy to achieve optimal response in a given patient, we examined the possibility of using telomerase for this purpose in colorectal cancer. Telomerase, a ribonucleoprotein enzyme complex catalysing synthesis of chromosome ends (telomeres), has been known as an almost universal tumor marker but its predictive value has been found in only a limited number of malignant tumor types. Telomerase activity and expression of its catalytic subunit hTERT was determined in 82 surgical specimens from 41 patients (a sample of tumor tissue and of adjacent morphologically normal tissue was obtained from each patient). Telomerase activity was present in tumor samples from 34 (83%) patients, reaching an average value of 47.6 telomerase units (T.U.), while adjacent tissue specimens were either negative (in 25 (61%) patients), or slightly positive (in 16 (39%) patients) showing 1.5 T.U. on average. In tumor samples from patients without lymphatic node metastases (pN0), an average of 37.1 T.U was found. In contrast, in tumor samples from patients with lymphatic node involvement (pN1 or pN2) the average activity was significantly higher (60.2 T.U., p<0.05). In patients with distant metastases a tendency towards higher telomerase activity, although lacking statistical significance, could be observed. Among patients that obtained chemotherapy with 5-fluoruracil, those with low telomerase activity showed a tendency to chemosensitivity. Expression of hTERT was detected not only in samples showing telomerase activity, but also in a considerable portion of telomerase-negative samples either from the tumor or the adjacent normal tissue. We demonstrate that some of these apparent discrepancies may be attributed to differential splicing of hTERT mRNA. We conclude that TRAP assay for telomerase activity is more informative than the common testing for hTERT expression. Telomerase activity is useful both as a diagnostic as well as a predictive factor in colorectal cancer.     

A lethal course of hypertrophic cardiomyopathy in Noonan syndrome due to a novel germline mutation in the KRAS gene: case study

Noonan syndrome is a relatively common and heterogeneous genetic disorder, including congenital heart defect in more than half of the cases. If the defect is not large, life expectancy is normal. Here we report on a case of an infant with Noonan syndrome and rapidly progressive hypertrophic cardiomyopathy with lethal outcome, in whom we identified a novel mutation in the KRAS gene. This heterozygous unclassified missense variant in exon 3: c.179G>T (p.Gly60Val) might be associated with a lethal form of Noonan syndrome. The malignant clinical course of the disease and the lethal outcome in an infant only a few months old might be connected to RAS-mitogen-activated protein kinase pathway hyperactivation, consequently promoting cell growth and proliferation, leading to rapidly progressive hypertrophic cardiomyopathy. Further biochemical and functional studies are needed to confirm this hypothesis.Noonan syndrome (NS; http://www.omim.org/entry/163950?search=163950&highlight=163950) is a relatively common genetic disorder with an incidence of 1 per 1000-2500 live births (1). Clinically it is a very heterogeneous disorder, predominantly characterized by dysmorphic facial features, congenital heart defect (CHD), post-natal short stature, webbed neck, chest deformity, cryptorchidism in men, lymphatic dysplasia, variable bleeding disorders, and intellectual disability. CHD is present in 50 to 80% of affected individuals and it is also very heterogeneous (2). Most commonly found are pulmonary valve stenosis with or without dysplastic pulmonary valve and hypertrophic cardiomyopathy. Providing the CHD is not large, life expectancy is in the normal range (3). NS and CHD are regularly connected with germline KRAS mutations. We describe a patient with NS and rapidly progressive hypertrophic cardiomyopathy with lethal outcome, in whom we identified a novel mutation in the KRAS gene.