Three-compartment pharmacokinetic models of radiotracers used in the GFR-determination - estimation of their parameters using the time-concentration curves.

BACKGROUND: In GFR measurements with radiotracers, there is evidence that a two-compartment model is unable to describe the full plasma curve, including early time points, but analyses generally focus on two-compartment models. AIMS: To analyze both the mammillary and catenary three-compartment model and to determine empirical relations between model constants and the overall GFR and ECV (extra-cellular volume). MATERIAL AND METHODS: Mathematical analysis of the three-compartment model. Full-curve patient data from 32 adults and 7 children were used to relate model parameters to GFR and ECV. RESULTS: Model volumes were found to be roughly proportional to ECV. In both models, the central (plasma) volume was V1 = 0.24 × ECV and elimination rate from V1 was k10 = 4.2 × GFR/ECV. In the mammillary model, the two parallel volumes were V2 = 0.28 × ECV, V3 = 0.48 × ECV, and intercompartmental clearances were Cl12 [mL/min] = 0.0058 × ECV [mL], Cl13 = 0.042 × ECV. In the catenary model, the serial volumes were V2 = 0.60 × ECV, V3 = 0.16 × ECV, with clearances Cl12 = 0.048 × ECV, Cl23 = 0.0036 × ECV. CONCLUSION: Insight into the three-compartment model was achieved, and empirical relations to ECV and GFR/ECV were determined.

Derivation and presentation of formulas for drug concentrations in two-, three- and four-compartment pharmacokinetic models.

Although compartment models are frequently used in pharmacokinetics, it is difficult to find complete analytical formulas describing the behaviour of drugs in universal simpler compartment models in the accessible literature. The paper presents derivations of formulas for general two- and three-compartment models, including the possibilities of original non-zero quantity in all compartments and elimination from all compartments. Formulas for four-compartment models are also derived with the restriction that original quantity is non-zero in only one compartment. Derivation uses Laplace transformation but does not require prior knowledge of the technique. The derived analytical formulas are verified numerically. These formulas can be easily simplified to less complex cases.

Bone scintigraphy hot-spot in projection to rib and kidney: role of single photon emission computer tomography/computer tomography in distinguishing a urine collection in renal calyx from a metastasis to rib.

On planar bone scintigrams, activity enhancement foci in projection to kidney and lower ribs can arise from the kidney, or from bone lesions. A differentiation based only on the exact location and shape of the hot spot can sometimes be misleading, resulting in a false qualification of a rib metastatic lesion as urine collection in the kidney or opposite. The authors illustrate the problem with three cases: In two patients, such a hot spot appeared to be the solitary metastatic focus; in one, highly suggestive for solitary metastatic focus, it was proven to be a urine collection.

Approximation of time-uptake curve to a modified Bateman equation based on three uptake tests - potential value for dosimetry of corpuscular radiation.

BACKGROUND: Many models of assessing radiopharmaceutical kinetics for dosimetry have been developed, starting from the formula of Marinelli. They are either inaccurate or require taking multiple patient uptake measurements. MATERIAL AND METHODS: Radiotracer behavior is approached to a modified Bateman equation ("biphasic model"). The calculated effective half time, maximum uptake and the cumulated uptake according to the biphasic model is compared to the values obtained with the most popular Marinelli's method ("simplified model"). The calculations can be performed by free online-accessible software on the site: www.nuk.bieganski.org ("Calculator"). RESULTS: Using of the software allows a direct comparison of the obtained effective half times according to both, the simplified and the biphasic, models. Further errors can come from imprecise measure of the maximum uptake value (especially, when the time of the measurement differs from the true point of the maximum uptake) and from neglecting of the ascending branch of the time-uptake curve. It is possible to compare the cumulated uptake values according to both models ("correction factor"). The results can be combined with the widely known formula of Marinelli. The operations require only one additional uptake measurement, which could be performed shortly after the i.v. administration of the radiotracer, i.e., during the same visit of the patient. CONCLUSION: The proposed theoretic model could be verified practically for some i.v.-administered radiopharmaceuticals.

Enhanced accumulation of bone seekers at superior lateral orbital margin: potential origin.

Enhanced accumulation of the radiotracer at superior lateral orbital margin is a common finding in bone scintigraphy. Its possible sources are discussed and illustrated with examples from own archive of the authors as well as from the literature. These sources include: Physiologically enhanced bone metabolism at frontozygomatic suture (normal variant), a metastasis at this suture (illustrated with an example of solitary metastasis from prostate cancer), lesions to the zygomatic bone or the greater wing of the sphenoid bone, deepened fossa for lacrimal gland and the gland itself.

Congenital vascular malformations in scintigraphic evaluation.

BACKGROUND: Congenital vascular malformations are tumour-like, non-neoplastic lesions caused by disorders of vascular tissue morphogenesis. They are characterised by a normal cell replacement cycle throughout all growth phases and do not undergo spontaneous involution. Here we present a scintigraphic image of familial congenital vascular malformations in two sisters. MATERIAL/METHODS: A 17-years-old young woman with a history of multiple hospitalisations for foci of vascular anomalies appearing progressively in the upper and lower right limbs, chest wall and spleen. A Parkes Weber syndrome was diagnosed based on the clinical picture. Due to the occurrence of new foci of malformations, a whole-body scintigraphic examination was performed. A 12-years-old girl reported a lump in the right lower limb present for approximately 2 years, which was clinically identified as a vascular lesion in the area of calcaneus and talus. Phleboscintigraphy visualized normal radiomarker outflow from the feet via the deep venous system, also observed in the superficial venous system once the tourniquets were released. In static and whole-body examinations vascular malformations were visualised in the area of the medial cuneiform, navicular and talus bones of the left foot, as well as in the projection of right calcaneus and above the right talocrural joint. CONCLUSIONS: People with undiagnosed disorders related to the presence of vascular malformations should undergo periodic follow-up to identify lesions that may be the cause of potentially serious complications and to assess the results of treatment. Presented scintigraphic methods may be used for both diagnosing and monitoring of disease progression.

To what extent can diverse types of liver lesions mimic hemangiomas? A retrospective quantitative analysis of masses found to be positive in SPECT/CT with labeled blood cells - a preliminary report.

BACKGROUND: Although specificity of SPECT/CT examination using technetium-99m radiolabeled red blood cells (Tc-99m-RBC) for detection of liver hemangiomas is very high, it is still not perfect. It is possible to overlook a malignancy. Moreover, the difference in accumulation of RBCs between a hemangioma and uninvolved liver remains unknown. The aim of the study is to determine the quotients of accumulation of Tc-99m-RBC in hemangiomas and in normal liver parenchyma (HEM/liv), and to verify, whether the quotient could be potentially helpful in distinguishing hemangiomas from other RBC-accumulating liver masses. MATERIAL/METHODS: 34 liver lesions larger than 1.5 cm classified scintigraphically (qualitatively) in our Department as either typical or suspicious of hemangioma 1.5-4 years earlier were enrolled in this retrospective study. Their SPECT/CT images were acquired 1 hour after in vivo labeling of RBCs with Tc-99m. In reconstructed images, ellipsoidal regions of interest (ROIs) with diameters of about 1.5 cm were created in the assessed lesions (HEM) and in the uninvolved liver parenchyma (liv). The HEM/liv quotients were calculated for each mass. The results were compared with radiological data. RESULTS: 31 lesions were found to be clinically and radiologically typical for hemangiomas, their HEM/liv ratios were at least 1.6 (smaller masses) or 1.8 (larger masses). One lesion with HEM/liv ratio equal to 1.21 was classified as metastasis. Two lesions with HEM/liv 1.42 and 1.46 were classified as benign foci other than hemangioma. CONCLUSIONS: The quantitative analysis can be preliminarily proposed as a helpful tool in the assessment of possible liver hemangiomas.

Two hundred years after discovery of iodine--less known functions of the element in human organism.

The main role of iodine in human organism is related to biosynthesis of thyroid hormones. The less known metabolic pathway of the element is formation of iodolipids (mainly iodoaldehydes and iodolactones). One of the compounds, 6-iodo-5-hydroxy-eicosatrienoic acid delta-lactone (6-IL), is believed to inhibit goiter growth, to modulate the cell response on some growth factors, and to trigger apoptosis in some types of cells. Another one, 2-iodohexadecanal (2-IHDA), probably also inhibits goiter growth and mediates the Wolff-Chaikoff-effect. Epidemiological and experimental data suggest a relation of iodine to some tumor diseases. Preventing of iodine deficiency diminishes prevalence of goiter as well as some non-goiter diseases.

FDG-PET/CT in lung cancer: an update.

The prognosis of lung cancer patients mostly depends on the stage at which the disease is diagnosed. Contrast-enhanced CT (ceCT) and MRI play a significant role in initial staging, but often the morphological information is insufficient when compared to the metabolic or molecular information obtained by positron emission tomography (PET). [18]F-fluorine deoxyglucose (FDG) is based upon the increased demand of ATP leading to increased consumption of glucose in the tumor tissues. FDG-PET/CT has been proven to be of immense value in the initial diagnosis, evaluation of therapy reponse, detection of recurrent tumor, radiation therapy planning and in the multidisciplinary management of patients with non-small cell lung cancer as well as in patients with small cell lung cancer. The aim of this article is to present a concise summary of the present status of FDG-PET/CT.

[What is the origin of cerebral aneurysms?]. / Skad sie biora tetniaki tetnic mózgowych?

Authors reviewed the literature on the ethology of saccular cerebral aneurysms. Nowadays the theories about inborn origin of the aneurysms are refuted. Numerous factors are involved in their formation. Two considered groups of the factors are the following: the hemodynamic ones and the ones related to particular cerebral artery histology. The first group comprises arterial hypertension and arterial blood flow disturbances in the brain. They increase the hemodynamic stress on arterial bifurcations. It has been also proven in the regions that the stagnation of blood flow may take place. It may induce a local arterial wall injury which may be caused either by anoxemic mechanism or by the release mediators from blood cells. The main factor in the second group is the particular make up cerebral artery walls, especially regions around their bifurcations, where a predominance of collagen fibers over elastic ones is found in connection with poorly developed muscular layer. The existing defects may be enhanced by disturbances in the process of connective tissue proteins synthesis which may be influenced by numerous endo- and exogenic factors. Apart from the genetic ones they may include: poisons like heavy metals and toxins present in cigarette smoke, medicines and hormones, especially steroidal ones. Unfortunately, experimental studies documenting the interdependencies between those substances and aneurysms are still scarce. Statistically proven risk factors of the malformations include: cigarette smoking, untreated arterial hypertension, female gender, collagen synthesis disturbances, and any disturbances in cerebral blood flow.

[Surgical treatment of Parkinson's disease]. / Chirurgiczne leczenie choroby Parkinsona.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Its pathogenesis is based on diminution of neurons in substantia nigra, that under normal conditions acts as the source of dopamine in nigrostriatal circuit. The decline of dopamine concentration caused by death of dopaminergic neurons is responsible for the appearance of symptoms typical for the mentioned disease. Along with pharmacotherapy, with its most impressive success - that is delivery of the precursor of dopamine (L-DOPA) to the central nervous system--surgical methods are developed for treatment of PD. The basis of these approaches consist of "switching off" the nigrostriatal structures that are overactive due to lack of inhibiting action performed normally by dopamine. Stereotactic neurosurgery - enabling safe access to the region of basal ganglia, thalamus and subthalamic nucleus can be an important solution for many patients with the PD unresponding to pharmacological therapy. Depending on the procedure irreversible lesions or stimulation leading to reversible block can be done in order to restore physiological functional conditions within nigrostriatal circuit. The new, experimental method of curing PD is transplantaton of dopaminergic rich neurons from fetal mesencephalic tissue. Despite very promising results, this procedure is very controversial due to ethical problems concerning aspects of fetal graft acquisition. In the authors' point of view, the only chance for making the concept of neurotransplantation applicable is the use of neural stem cells that are able not only to renew dopaminergic neuron population, but also, thanks to gene therapy--introducing key substances (e.g. thyrosine hydroxylase, glial cell line-derived neurotrophic factor) and elimination the cause of parkinsonian disturbances.

[Is the brain a postmitotic organ? -- current knowledge on neural stem cells]. / Czy mózg jest organem postmitotycznym?--stan wiedzy o nerwowych komórkach macierzystych.

All the attempts for regeneration in the central nervous system (in clinical conditions) are still a failure. Hence the bulk of clinicists are convinced that the brain is a postmitotic organ. Are the pessimists right? In the recent few years some knowledge break-throughs have been made. It has been noticed in many places of adult mammals' brains there are cells capable of proliferating, including asymmetric divisions, and differentiating into neurons and glia when suitably stimulated. Such cells, called neural stem cells, are present also in the brains of adult humans, especially in the subventricular zone. It has been recently discovered that also cells derived from bone marrow are capable of differentiating into neurons. The authors reviewed world-wide literature devoted to this topic. They focused mainly on the biology of the newly discovered cells, and especially on their mitotic and differentiating potential. The authors critically assess the discoveries discussed.

[Neural stem cells: perspectives of clinical application]. / Nerwowe komórki macierzyste--perspektywy zastosowan klinicznych.

The prognosis for many patients with central nervous system (CNS) diseases has recently improved, especially due to enormous development of medical sciences. Nevertheless there are still pathologies very difficult to cure. It is caused mainly by the irreversibility of CNS lesions, that even after ceasing the primary pathological process--lead to deep functional deterioration. Hopefully this will change in the future thanks to the discovery of the stem cell population located in the CNS. These cells have to reproduce cytoarchitecture and CNS function. The range of possible use of the therapy based on neural stem cells (NSC) appears unlimited. The most advanced laboratory trials are focused on neurodegenerative diseases with very promising results The second field of clinical neuroscience that NSC can play a key role in are injuries of the CNS, with special emphasis on spinal cord injuries which are still an unresolved problem of neurotraumatology. Adding to the possible roles of NSC--they may act as transporters of transgenes in case of metabolic or neoplasmatic diseases. The interest of many groups of scientists in biological and clinical use of NSC appears to be justified. Authors present advancement and possible ways of development of therapeutic methods based on NSC.

[Misdirected nerve regeneration: clinical implications]. / Nieprecyzyjna regeneracja nerwów--implikacje kliniczne.

Although peripheral nerve regeneration is not a precise renewal of primary connections, it often leads to successful return of their function. Moreover, in some cases, an injured nerve is aimly stitched to another one. A good example of such a procedure is intercostal neurotization of avulsed brachial plexus. Despite the fact that neural centers are not primarily suitable for their new function, they often fulfill it successfully. This respecification of function requires some changes in the central nervous system called "plasticity". Discussed are the potential mechanisms controlling these changes. The role of hypothetic proteins reversely transported from the target organ to the neuron's body, proprioceptive fibers and volitional control is mentioned. The punctual understanding of these mechanisms may appear not only very scientifically wonderful but also useful in clinical practice.