Lege Artis Medicinae

[A Poem Cycle by Zsuzsa Tamás – Pictures by Tímea Fodor]

MARCH 19, 2007

Lege Artis Medicinae - 2007;17(03)

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Lege Artis Medicinae

[BISPHOSPHONATES IN THE TREATMENT OF BONE METASTASES]

NAGYKÁLNAI Tamás

[Bisphosphonates are used in the treatment of malignant diseases with bone metastases and of osteoporosis. The currently available bisphosphonates have a wide range of effectiveness, tolerability and dosing profiles. In metastatic disease, bisphosphonate therapy is aimed at the correction of hypercalcaemia and the reduction of skeletal-related events due to malignancy metastatic to bone. Large clinical trials have shown that long-term administration of bisphosphonates can reduce skeletal-related events by 30 to 40% and significant analgesic effect is reached in at least 50% of the patients. The superiority of zoledronate to the old standard pamidronate has been proved in large randomized trials. Despite the fact that bisphosphonates are generally well tolerated, certain toxicities such as renal toxicity and osteonecrosis of the jaw should be considered with prolonged use.]

Lege Artis Medicinae

[THE ROLE OF SIMVASTATIN IN THE TREATMENT OF DIABETIC DYSLIPIDAEMIA]

BALOGH Zoltán, PARAGH György

[Patients with type 2 diabetes have markedly increased cardiovascular morbidity and mortality. Type 2 diabetes is typically associated with atherogenic dyslipidaemia, which is characterized by elevated triglycerides, low plasma levels of high-density lipoprotein cholesterol, and an increased ratio of small, dense lowdensity lipoprotein particles. Current treatment guidelines stress the importance of lipidlowering therapy in reducing cardiovascular risk in diabetic patients. Statins currently represent the cornerstone of dyslipidaemia management, based on their ability to efficiently reduce cardiovascular risk through lowering low-density lipoprotein cholesterol. They have, however, a relatively modest effect on the components of atherogenic dyslipidaemia, since they reduce triglycerides by only 15 to 35% and elevate high-density lipoprotein cholesterol by less than 10%. This raises the need for combining statins with other lipid-lowering drugs (ezetimibe, nicotinic acid, fibrate) at an early stage of type 2 diabetes. Authors review the role of simvastatin monotherapy in the treatment of diabetic dyslipidaemia and summarize the results of studies on simvastatin as part of a combined lipid-lowering treatment.]

Lege Artis Medicinae

[The Command of Self-Awareness Work A Discussion with dr. Emőke Bagdy]

FERENCZI Andrea

Lege Artis Medicinae

[From pharmacogenetics to ecogenomics]

SCHLAMMADINGER József

Lege Artis Medicinae

[Cesarean Section in Islamic Culture]

dr. SZABÓ András

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Clinical Neuroscience

[Differential diagnosis of atypical Parkinsonian syndromes]

CSÓTI Ilona, FORNÁDI Ferenc

[Atypical Parkinson syndromes are distinguished from idiopathic Parkinson disease by insufficient or missing response to dopaminergic replacement therapy and therefore they have significantly unfavorable prognoses. Early differential diagnosis is very important for the patient. It enables the therapist to give suitable consults, to avoid unnecessary or inappropriate therapy, which are not free of medication side effects and furthermore facilitates the selection of adapted symptomatically medical and physical measures of treatment. In case of future development of neuroprotective or causally therapy strategies correct diagnosis will allow an early start of therapy. The differential diagnosis separation of the three clinical pictures from the idiopathic Parkinson disease with clinical criteria might be difficult in the early stage of disease. Additional neuroimaging and nuclear medical investigations may support the clinical probable diagnosis.]

Hungarian Radiology

[Ethiopathogenesis of polycystic ovarian syndrome and imaging diagnostics of polycystic ovary]

ifj. JAKAB Attila, MOLNÁR Zsuzsanna, TÓTH Zoltán

[Polycystic ovarian syndrome is a heterogenous syndrome with a wide variety of endocrine and metabolic abnormalities and clinical symptoms. It is considered as the most frequent endocrine disorder in women in reproductive age and the most common cause of anovulatory infertility. Key features include menstrual cycle disturbance, hyperandrogenism and obesity. There are many extraovarian aspects to the pathophysiology of polycystic ovarian syndrome, but ovarian dysfunction is central. The underlying unique feature of the ovarian morphology gives the significance of the ultrasound examination. At a recent consensus meeting, a refined definition of the polycystic ovarian syndrome was agreed, encompassing a description of the morphology of the polycystic ovary. The subjective appearance of polycystic ovary should not be substituted for the definition. Further, a woman having polycystic ovary in the absence of menstrual disorder or hyperandrogenism (asymptomatic polycystic ovary) should not be considered as having polycystic ovarian syndrome, until more is known about the situation. Since ultrasound description of polycystic ovary morphology has central role in the diagnosis, and untreated polycystic ovarian syndrome carries long term health risks, the increasing attention to ovarian morphology may offer an effective tool to decrease women`s morbidity. This review outlines the background and feature of ovarian morphology in polycystic ovarian syndrome, and details the current ultrasound definition of polycystic ovary.]

Clinical Oncology

[Cell cycle as therapeutic target – CDK4/6 inhibition]

KOPPER László

[One of the most important decision of a cell: to live or die. If survival is the choice, there are three options: proliferate, to stay in sleeping state for a while, or differentiate in order to perform its specifi c function. These decisions are under a very strict molecular regulation infl uenced by internal and external factors. Tumor cells more and more disregard the regulations, and move into independency for a continuous proliferation, which has a very similar program in normal and tumor cells. The main route towards mitosis is the cell cycle, under the supervision of positive and negative regulators, forming checkpoints, telling to the cell - under the infl uence of mitogenic signals - to go or to stop. The most critical checkpoint is at the border of G1 and S phases where the main players are cyclinD, CDK4/6 and RB1. It turned out that the best targets to inhibit cell proliferation are the CDKs, but this approach, when used unselected targets, was unsuccessful due to the toxicity. To improve the clinical results, the selection of CDK4/6 as a therapeutic target seems to fulfi l most of the hopes. Today three drugs are the most promising: palbociclib (with an acceptance by FDA and EMA to treat breast cancer patients), abemaciclib and ribociclib (underclinical trials). Now, most of the data concern breast cancer, especially the combinations of CDK4/6 inhibitors and endocrine therapy, but many other malignancies are studied (e.g. liposarcoma, mantel cell lymphoma, melanoma, renal cancer, lung cancer, pancreatic cancer, ovarian cancer, teratomas etc.). The key points are the side-effects, the most frequently observed is neutropenia, but so far it is managed without serious toxicity.]

Hypertension and nephrology

[The history of diuretic treatment in Hungary. Part I. Imre Fodor]

RADÓ János

[The diuretic effect of mercurial compounds was discovered in 1920. However, the term of “mercurial diuresis” was created 36 years earlier by Ernő Jendrassik. Imre Fodor published his experiences with the mercurial diuretic, which has been cited by several authors worldwide. The Hungarian pharmaceutical industry also took its part from the production of the mercurial diuretic with Novurit that proved to be an excellent and worldwide well known preparation in the next 40 years. Even Imre Fodor required the repeated administration of mercurial diuresis because of his severe cardiac oedema in the last period of his life. When the drug became ineffective, i.e. developed refractory oedema, he made a “self-experiment” with the administration of ACTH to restore the sensitiveness to the mercurial diuretic on the basis of most recent American literature at that time. His experience has been published by his colleagues just before his death. Imre Fodor was an eminent clinician, a school creating internist who entered his name into the science dealing with the use of diuretics.]

Clinical Oncology

[Hematopoietic stem cell transplantation for solid tumors in adults]

GOPCSA László Zsolt, MASSZI Tamás

[We revised the medical literature regarding autologous and allogeneic hematopoietic stem cell transplantation (HSCT) in the setting of solid tumors. Autologous-HSCT for solid tumors in adult patients show changing patterns in past decades with decreases numbers for many types of solid tumors. Most marked is the previously well-described increase and decrease in autologous HSCT for breast cancer (BC). Autologous-HSCT for BC has been an area of intense controversy. The role of autologous-HSCT for BC at high risk of recurrence (at least four involved axillary lymph nodes) has been assessed by several randomized trials. Overall, it was shown that high-dose therapy prolonged disease-free survival when used as adjuvant therapy, and showed a benefi t on overall survival in only selected cohorts of patients. In second or further relapsed or primary refractory germ cell tumor, highdose therapy is considered to be a standard therapeutic option, especially when poor prognostic factors are present. In addition, sequential therapy with two to three cycles is felt to be superior to single cycle of HSCT. High-dose therapy can be regarded as a potential clinical option in selected adult patients with Ewing’s sarcoma and medulloblastoma. Currently, in other types of solid tumors the autologous- HSCT is generally not recommended or developmental and only used in the context of prospective studies. Numbers of allogeneic HSCT for solid tumors remained stable low number throughout the recent years. Transient increase is observed over the last decade and is primarily due to renal cell carcinoma, BC and colon cancer. Concepts of allogeneic HSCT for solid tumors do not rely on highdose chemotherapy and tumor load reduction but rather on a graft-versus-tumor effect. Attempts to improve the therapeutic effect of allo-HSCT or other cellular therapies in solid tumors by innovative clinical strategies are underway.]