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[The female athlete triad].

This review offers some basic information on a syndrome described in 1992 as the female athlete triad. The increasing participation of women in competitive sports has led to significant accumulation of knowledge about potential pathological conditions due to strenuous exercise. Participation in sports that emphasize specific body image, psychological constitution of young female athletes and significantly lower daily calory intake cause the development of disordered eating, especially anorexia nervosa. Anorexia in combination with intensive training induces menstrual disorders, exercise-associated amenorrhea being the most important one. Low serum estrogen concentrations, as well as insufficient daily calcium intake have negative influence on bone mineral density, and the athletes have greater risk of developing osteoporosis and stress fractures. We described the diagnostic and therapeutic procedures necessary to detect and treat this syndrome. Education of physicians, female athletes and their coaches, as well as the screening during the annual examination, remain the most important measures of prevention.

Amenorrhea↗

Hospital discharge of patients with thyroid carcinoma treated with 131I.

UNLABELLED: A dose limit-based criterion was proposed to authorize hospital discharge of thyroid carcinoma patients treated with 131I. Evaluation of accumulated doses to determine the effective half-life, the expected accumulated dose at 1 m, and the hospitalization time was performed to ensure that the dose limit was satisfied for each patient. Situations involving different dose limits and occupancy factors were analyzed. This study dealt only with external exposure; the problem of internal contamination was not considered. METHODS: Fourteen patients treated postoperatively with 131I were studied. The range of activity was 1,110-8,175 MBq. Electronic dosimeters and thermoluminescent dosimeter chips were placed on the left pectoral muscle. Dose was measured for a mean of approximately 2.5 d. The accumulated doses were plotted as a function of time and then fitted using an exponential model to obtain the parameters of total accumulated dose and effective half-life. The doses to the public and relatives at 1 m were calculated with point source approximation and several occupancy factors. RESULTS: The fit function parameters of accumulated doses in the first 36 h predicted the behavior of the total accumulated dose within a 5% error in the parameters. Estimated values of the accumulated dose 1 m from the patient were generally <5 mSv, even for an occupancy factor of 100%. For more restrictive dose constraints, hospitalization times were calculated according to different occupancy factors, as suggested in the European Commission guide. From the fit of the measured data, values of effective half-life for each patient were obtained. CONCLUSION: To apply the dose limit-based criterion, one must calculate the patient-specific parameters, as can be done using the accumulated dose. Knowledge of patient-specific parameters ensures that the patient will not expose any individual to levels greater than the dose limit. The calculated hospitalization times were less than those recommended, especially for countries with more restrictive dose limits. The type of measurements performed in this study reveals more realistic doses for the treatment of thyroid carcinoma with 131I.

Adolescent↗

Liver regeneration: the emergence of new pathways.

The present overview summarizes important knowledge having accumulated during the last years. The liver maintains a steady mass which is basically controlled by a delicate balance between cell gain and cell loss. However, reconstitution of the organ after tissue loss does not only involve replacement of target cells, but also complex remodeling processes resulting in the reconstruction of the typical tissue architecture. Most information in liver regeneration refers to hepatocytes. It is important to note that hepatocytes are not terminally differentiated cells, but cells situated in the G0 phase that can undergo proliferation upon appropriate stimulation. In most situations, hepatic stem cells are not significantly involved in this response. Hepatocyte regeneration is accomplished by a sequence of distinct phases: an initiation phase, rendering cells in a state of replicative competence; a proliferation phase, where expansion of the cell population occurs; and a termination phase, where cell growth is suppressed to terminate regeneration at a set point. These three phases are regulated by a whole group of factors, mainly cytokines, the significance of which has in part been defined by use of animal models with target gene deletions (gene knockouts). It seems that several mechanisms are capable to sense the critical cell mass which has to be achieved. Hepatocyte regeneration is accompanied by a complex remodeling of hepatic tissue, with a transient breakdown of the lobular architecture. In contrast to hepatocytes, less is known for the the regenerative replacement of bile ducts, blood vessels and hepatic stellate cells.

Animals↗

Molecular-pathogenetic classification of genetic disorders of the skeleton.

Genetic disorders of the skeleton (skeletal dysplasias and dysostoses) are a large and disparate group of diseases whose unifying features are malformation, disproportionate growth, and deformation of the skeleton or of individual bones or groups of bones. To cope with the large number of different disorders, the "Nosology and Classification of the Osteochondrodysplasias," based on clinical and radiographic features, has been designed and revised periodically. Biochemical and molecular features have been partially implemented in the Nosology, but the rapid accumulation of knowledge on genes and proteins cannot be easily merged into the clinical-radiographic classification. We present here, as a complement to the existing Nosology, a classification of genetic disorders of the skeleton based on the structure and function of the causative genes and proteins. This molecular-pathogenetic classification should be helpful in recognizing metabolic and signaling pathways relevant to skeletal development, in pointing out candidate genes and possible therapeutic targets, and more generally in bringing the clinic closer to the basic science laboratory and in promoting research in this field.

Bone Diseases, Developmental↗

[Phylogeny of Triticum L. and Aegilops L. genuses inferred from a comparative analysis of nucleotide sequences in promoter rDNA regions of individual species].

The process of accumulation of knowledge on wheat and related wild species during the 20th century is briefly reviewed with special reference to the evidence of the recent years on evolution of polyploid wheats and the role of diploid species. The latter serve as potential donors of the genomes, detection of which is particularly important because of the continuing speciation in the tribe Triticeae and artificial development of synthetic forms. The arguments in favor of the donor role for various diploid wheat species and aegilopses from the section Sitopsis are compared. It is stated that in the formation of the both lines of polyploid wheats turgidum-aestivum and timopheevi, diploid Aegilops speltoides acted as a maternal form. In addition to plasmatic genomes, this aegilops species introduced into them also the B and G nuclear subgenomes. A comparison of nucleotide sequences in the variable part of the promoter of evolutionary conserved rRNA genes in polyploid wheats with their counterparts in diploid wheats and aegilopses confirmed the accepted wheat phylogenies.

Base Sequence↗

[Surgical education in medical school].

Progress of medicine and technology is quick. Accumulation of knowledge is immense and advancement of surgical technologies is vast. Curriculum and methods of surgical education in medical school should be modified accordingly. Our society has not actively participated in surgical education in medical school but considering the importance of surgical education in medical school for the future of surgery and surgical practice, and society (JSS) should more actively participate in surgical education for medical students by starting a special committee for this particular purpose within the society. A desirable curriculum in surgical education in medical school is presented.

Education, Medical, Undergraduate↗

[Outcome predictors in patients with normal pressure hydrocephalus].

Despite the accumulation of knowledge over the years, the postoperative results of shunt implantation in patients with normal pressure hydrocephalus (NPH) have shown little improvement. This means that reliable predictors of the course of the disease need to be identified. In a prospective study carried out between 1982 and 2000 we re-examined 155 (78%) of 200 NPH patients treated by shunt implantation, 7 months after their operation. On the basis of the results of the intrathecal infusion test NPH was graded early stage (no brain atrophy) or late stage (brain atrophy). We looked at the following factors as possible predictors: patient's age, disease duration, idiopathic or secondary aetiology, clinical signs such as gait ataxia, dementia and urinary incontinence, results of spinal tap, valve type and valve infection, and resistance to cerebral spinal fluid outflow and postoperative changes in ventricular size. As a measure for outcome we used the NPH recovery rate, and the Pearson chi-square test for statistical evaluation. 80 patients with early stage NPH, a history < 1 year, absence of dementia and an implanted Miethke dual-switch valve proved to be significant predictors of a positive outcome. Outflow resistance proved to have only minimal impact on outcome. The 75 patients with late-stage NPH had better outcome when dementia was absent, outflow resistance was > 20 mmHgmin/ml, the CSF tap test was positive, and a Miethke dual-switch valve was implanted.

Atrophy↗

[Regulation of proliferation and differentiation of hematopoietic cells by cytokines].

Recent studies on the hematopoietic system have revealed that both constitutive and inducible hematopoiesis are regulated by complicated networks composed of various kinds of cytokines and that there are some general rules for hematopoietic cytokine biology. Further accumulation of knowledge about the regulation of proliferation and differentiation of hematopoietic cells by cytokines will serve to clarify the pathophysiology of hematological diseases, resulting in the development of therapeutic strategy for these diseases.

Cell Differentiation↗

[Structure, function and the role of factor XIII in human pathology].

Modern views on the functioning of coagulation system are constantly replenished with the facts obtained using the newest methods of molecular biology and medicine. The purpose of many components of this system is non-uniform and covers the whole spectrum of biochemical reactions responsible for homeostasis. Current data on one of such components--the factor XIII (fibrin stabilizing factor) are stated. Except for the description of the enzyme structure and functions, information is presented about the methods of its detection, which development has resulted in accumulation of knowledge on the role of fibrin stabilizing factor in bleedings and thrombosis genesis. Data are given on hereditary and acquired deficiency of the factor XIII, as well as on conditions accompanied with the increase of its activity.

Blood Coagulation↗

A new concept of skeletal dysplasias.

The skeletal dysplasias form a large group of hereditary disorders characterized by abnormal growth and malformations of bone and cartilage. The clinical severity ranges from mildly affected short stature to lethal forms. Spranger classified approximately 200 different skeletal dysplasias in 1992, based on the clinical and radiographic features and the mode of genetic transmission. Etiopathogenesis of skeletal dysplasias is better documented now, with rapid accumulation of knowledge concerning defective genes and proteins causing this group of disorders. Mutations responsible for skeletal dysplasias may cause defects in the synthesis of structural proteins and in metabolic pathways, degradation of macromolecules, growth factors and receptors and transcription factors. Classifications by the International Working Group on Constitutional Diseases of Bone were based on the mutations in the same group gene taking into consideration the clinical and radiological findings (achondroplasia group, dysplasia with decreased bone density group and type II collagenopathies...). Clinical manifestations and radiological investigations are crucial for the differential diagnosis in skeletal dysplasias. However, prenatal diagnosis and postnatal definitive diagnosis are most often achieved by molecular analysis of the patient. Therefore, these groups of disorders require management by a multidisciplinary team of specialists, including pediatricians, genetic specialists, orthopedists and psychiatrists.

Bone Diseases, Developmental↗

[Supplementary sensory-motor seizures--symptomatology, etiology, and surgical management with illustrative case reports].

In the past decade, owing to the advance of epilepsy surgery, growing knowledge has accumulated on the role of the supplementary motor area, described by Penfield and coworkers in the early fifties, in movement regulation and on the characteristics of seizures involving this area. In the Hungarian neurological literature this topic--despite its neurophysiological and practical clinical importance--has been hardly touched. The authors, based on their own experience obtained from surgeries performed within the framework of the "Co-operative Epilepsy Surgery Program", describe the electrophysiological features of this area, its role in movement regulation and the symptoms of epileptic seizures stemmed from or spread onto this area. Using cases as illustrations, they demonstrate the reasoning and various algorithms of the multidisciplinary examination necessary to explore the seizure onset zone and the pathways of seizure spread. Details of the surgical solution are also described.

Adolescent↗

[Epidemiologic, pathologic, diagnostic and clinical features and therapy of Helicobacter pylori infection based on latest data].

Helicobacter pylori is one of the most common human microorganisms. The outcome of its acquisition is not predictable, nevertheless a great amount of knowledge has accumulated concerning the virulence factors of the bacteria and the diseases associated with the infection. In most cases, this indigenous bacterium of the human stomach does not cause serious illnesses and the consequences of the infection depend on host and environmental factors. A more comprehensive insight into bacterial pathogenic and immunogenic mechanisms and host immune response may result in a more reasonable, cost-effective therapy and disease prevention.

Anti-Bacterial Agents↗

The application of the theory of systems in internal medicine. State of the art and perspectives.

The application and contribution of Cartesian methodology to the development of medicine in physiology, pathophysiology and therapy have been overwhelming. The accumulation of knowledge over the last 3 centuries in scientific research is largely attributed to Cartesian methodology. This method, which in the past was used for the acquisition of nosological data is no longer sufficient for the interpretation of complex phenomena which modern science nowadays requires. The solution to these complex problems is only possible by means of the application of the theory of systems especially for the functional evaluation of biological feedback.

Feedback↗

Lack of permissivity of human monoclonal CD4+ lymphocytes to HIV.

Although knowledge has accumulated about GP110-CD4 interaction, viral penetration into human CD4+ lymphocytes remains unclear, in spite of the fact that all studies on HIV infection were performed on cell-transformed lineages, or on human polyclonal CD4+ cells. In order to investigate this viral entrance into susceptible cells, we studied the permissivity of 13 human monoclonal CD4+ lymphocytes by means of reverse transcriptase (RT) assay and immunocapture. We demonstrated a differential susceptibility to HIV of these CD4+ clones. In a second experiment, HIV infection was studied: (1) sequentially by RT assay and P24 immunocapture on several clones; (2) by cocultivation of infected clones with umbilical cord lymphocytes. These experiments suggested existence of permissive and "nonpermissive" CD4+ monoclonal lymphocytes. Slot blot, then PCR, revealed that proviral DNA sequences were detectable in all clones, but were present at lower levels in nonpermissive clones.

Antibodies, Monoclonal↗

The tissue metalloproteinase family and the inhibitor TIMP: a study using cDNAs and recombinant proteins.

Loss of connective tissue integrity occurs in many disease processes, including rheumatoid arthritis and osteoarthritis. Although there is a high incidence of these diseases in the developed world, there is no treatment that prevents the tissue damage that occurs. Several lines of evidence suggest that uncontrolled connective tissue metalloproteinase activity is responsible for the damage, and as a consequence the inhibition of these enzymes has become the target for therapeutic intervention. Several connective tissue metalloproteinases, including collagenase, stromelysin, and gelatinase, together with tissue inhibitors of metalloproteinases (TIMPs), have been described. Because of difficulties in isolating the metalloproteinases in sufficient quantity as pure separate enzymes, however, very little knowledge has accumulated about their detailed biochemistry. For similar reasons the way in which TIMPs inhibit tissue metalloproteinases is not yet fully understood. In this article it is shown how cloning metalloproteinase and TIMP cDNAs can provide information about the structure of these enzyme and inhibitor families and how the cDNAs can be used to generate recombinant cell lines from which enzymes and inhibitors can be readily purified for further studies.

Amino Acid Sequence↗

[The role of inducing factors in early embryonic development].

In the field of early embryonic induction and differentiation we can observe an exponential increase of research activities over the last three years. The reasons for this rapid exploration are the application of powerful techniques of molecular biology and molecular genetics and the recent accumulation of knowledge about the close functional correlation between growth factors, embryonic induction factors, the products of oncogenes (or proto-oncogenes), and transcription factors. The highly probable role of the cellular and viral oncogenes in regulation of the differentiation and function of normal and malignant cells has stimulated the interest of scientists working on the molecular basis of malignant cell transformation. An excellent model to study mesoderm and neural induction and differentiation on the cellular and molecular level is the embryo of the south African clawed frog (Xenopus laevis), which is now a favored vertebrate system in many laboratories.

Animals↗

Rheumatic diseases in the U.S.S.R.

Despite our inability to precisely prognosticate disease, accumulation of knowledge about risk factors allows us to form a real basis for attempts at primary prevention of rheumatic disease. Because rheumatic diseases are multifactorial in nature, it may be suggested that the more factors an individual has the higher is the risk of disease. Relative risk values are certain to have a known limitation, since they are not independent. In addition, the number of risk factors may be significantly more than that known today. Increasing our knowledge in disease etiology and pathogenesis will definitely increase the number of risk factors. At the same time, available data may serve as a basis for developing a system for individual and group prognosis, the latter being to a certain degree tentative for the majority of diseases. All factors affecting disease development and course are divided into the controllable and the uncontrollable. The majority of the factors mentioned--especially, the environmental--are controllable ones. So the challenge facing practitioners and scientists involves development of a comprehensive system of recommendations aimed at elimination or maximum lessening of unfavorable risk factors, which is the only real basis for primary rheumatic disease prophylaxis.

Humans↗

Analytical review of structure and regulation of hemopoiesis.

Historical aspects of the accumulation of knowledge on the structure and kinetics of hemopoiesis are considered. Particular emphasis is placed upon kinetics of granulopoiesis based upon labeling of human granulocyte progenitors by tritiated thymidine (3HTdR) and the flow of labeled cells through mitosis and from a terminal mitosis through the non-dividing granulocytic pool into the blood. DNA synthesis time in myelocytes is 12-14 hours. The time from labeling of the myelocyte by 3HTdR to the appearance of labeled granulocytes in the blood is about 100 hours. Lobar pneumonia reduced the transit time from 100 to 48 hours in one patient. The deterministic model for granulopoiesis in human beings is described. Sterile inflammation and its effects on granulopoiesis was studied in the dog. Inflammation in tissue far from the bone marrow resulted in: 1. recruitment of a larger fraction of myelocytes into DNA synthesis; 2. increase in the rate of DNA synthesis in myelocytes; 3. increase in the number of mitoses in myelocytes; 4. increase in the rate of messenger transcription and translation so that a process involving synthesis of dozens of enzymes with their packaging into granules is shortened from 40 to 8 hours. It is likely that intramedullary production of GM-CSF and G-CSF are involved in the above processes. The nature of the chemical signal that mobilizes stored granulocytes from the marrow is not clear. Is there a factor produced in the inflammatory zone which circulates to the marrow and stimulates intramedullary production of GM-CSF and G-CSF? If so, are these the sole molecular regulators responsible for increasing the rate of granulopoiesis upon demand?

Animals↗