Detection of the sentinel node in breast carcinoma using method of a single subcutaneous injection of radiopharmaceutical.

The objective of this work is retrospective evaluation of results of the intraoperative detection of sentinel node in breast carcinoma after a single subcutaneous injection of radiopharmaceutical (RF) within a two-day protocol. From May/2001 to June/2002, lymphoscintigraphy of the sentinel node (SN) and its subsequent radioguided intraoperative detection (RGS) was performed in 43 women having stage T1-T2, N0 breast carcinoma. The static scans in the anterior and relevant lateral projections were performed using a gamma camera at approximately 30-minute intervals after the subcutaneous administration of 15 MBq 99mTc Senti-Scint, until the SN was displayed. The localization of the SN was marked on the overlying skin with a water-resistant permanent marker in 1-2 projections. RGS was accessed within 18-24 hours after the injection of the RF and all patients underwent an axillary dissection. The SN was detected in all patients, and in all cases was localized in the ipsilateral axilla. In 26 patients (60%), no metastatic process was found either in the SN or in any other axillary node. However, in one node, deposits of the carcinoma were detected in surrounding fatty tissue with propagation along the vessels and nerve. In 16 patients (37%), metastases in the SN were proved, in 7 cases (16%), a metastatic process was proved at the same time even in further lymph nodes. A number of false negative findings (5.8%) is consistent with the literature data. The method fails in the detection of intramammary localized SNs.

In vitro autoreactivity against skin and synovial cells in patients with juvenile idiopathic and rheumatoid arthritis.

In the present study we compared specific lysis of various autologous target cells in patients with juvenile idiopathic arthritis JIA; n = 8) or rheumatoid arthritis RA; n = 17) with those of healthy controls (n = 15). (51)Cr-release cytotoxic assay with autologous peripheral blood mononuclear cells as effector cells was used. When compared with controls, effector cells of patients with JIA or RA were found to lyse significantly autologous synovial cells (p < 0.0005) and epidermal keratinocytes (p < 0.0005), however, no difference was found for autologous dermal fibroblasts.

In vitro autoreactivity against skin in rheumatoid arthritis: are peripheral blood mononuclear cells of patients with rheumatoid arthritis able to lyze autologous keratinocytes?

An in vitro skin explant model was originally developed to predict the occurrence and severity of acute graft-versus-host disease in allogeneic hematopoietic stem cell transplants. In previous studies we reported that peripheral blood mononuclear cells of patients with rheumatoid arthritis were able to induce graft-versus-host-like histopathological changes when co-cultured in vitro with autologous skin explants. The aim of the present study was to verify if observed skin damage was really of autoimmune origin. Using a 51chromium release cytotoxic assay we found that peripheral blood mononuclear cells of patients lyzed autologous keratinocytes (n=5 patients with rheumatoid arthritis) but not autologous lymphoblasts (n=4 with rheumatoid arthritis, n=8 patients with juvenile idiopathic arthritis). No specific lysis of keratinocytes or lymphoblasts was observed in healthy controls (n=15). We hypothesize that autologous peripheral blood mononuclear cells might recognize similar autoantigen(s) expressed on epidermal cells, which gives rise to an autoimmune response in the synovium.

[Pharmacokinetic and therapeutic monitoring of gentamicin serum concentration in neonates]. / Badania nad farmakokinetyka I terapia monitorowana stezeniem gentamycyny we krwi u noworodków.

Pharmacokinetic analysis of gentamicin in 355 neonates hospitalized in the Clinical Dept. of Neonatology of the National Institute of Mother and Child in Warsaw was performed. The patients' group consisted of 119 premature and 236 full-term neonates, who were receiving gentamicin i.v. in the mean doses 4.461 +/- 0.921 ing/kg and 4.706 +/- 0.676 mg/kg, respectively. With use of the non-compartmental method, the following pharmacokinetic parameters were measured: biological half-life (t 0.5), elimination rate constant (k el), area under the curve (AUC), volume of distribution (V d) and total clearance (C T). Results differ considerably in term and preterm neonates and amount to: 11.25+/- 3.40 h-1, 0.0673 +/- 0.02 h-1, 233.7+/- 95.44 ug h/ml, 1.22 +/- 0.79 l/kg, 0.086 +/- 0.077 l/h/kg - for premature neonates versus 8.19 +/- 2.58 h, 0.089 +/- 0.02 h-1, 157.5 +/- 60.2 ug h/ml, 0.637 +/- 0.316 l/kg, 0.060 +/- 0.042 l/h/kg for full- term neonates. The analysis of pharmacokinetic parameters suggests that these findings may be already used as a preliminary basis of gentamicin population pharmacokinetics in both groups of neonates. The obtained results confirm that monitoring of gentamicin serum concentration helps to improve the treatment of neonates with this antibiotic. It was also found that the use of the dosing schedule of gentamicin with the dose intervals 36 or 48 h should guarantee adequate Cmax and Cmin without the need of routine monitoring of each patient in the premature neonate group.

Improved prediction of therapeutic absorbed doses of radioiodine in the treatment of thyroid carcinoma.

UNLABELLED: We proposed an alternative to a monoexponential model of radioiodine kinetics to obtain a more accurate estimate of absorbed doses to postsurgical thyroid remnants. We suggested that part of the difference between the predicted and the actually absorbed therapeutic doses of (131)I, usually explained by radiation damage of thyroid cells, can be attributed to errors resulting from inadequate sampling of data and oversimplified modeling. METHODS: A standard monoexponential model and alternative biphasic model (incorporating both radioiodine uptake and clearance) were used on 2 sets of patient data to fit time-activity measurements after administration of diagnostic and therapeutic activities of radioiodine. One set of data consisted of 633 records of routine measurements, and the second set consisted of 71 prospectively collected records with measurements performed more frequently and for a longer time. The time-activity curves derived from the 2 models were used to calculate residence times for diagnostic and therapeutic activities of (131)I, and the respective residence times were compared using the paired t test. Errors of fitting and prediction of therapeutic time-activity data were also calculated. RESULTS: With both models, a statistically significant difference (P < 0.01) was found between residence times after diagnostic administration of (131)I and residence times after therapeutic administration of (131)I. However, the effects of biphasic modeling and of improved sampling substantially reduced the difference (P < 0.01). Errors of fitting and prediction were smaller with the biphasic model than with the monoexponential model (P < 0.01). CONCLUSION: The biphasic model more accurately predicts (131)I kinetics when applied to measurements in the short interval after diagnostic administration of radioiodine. The minimum requirement for the biphasic model is measurement twice a day at intervals > 6 h for at least 3 d after administration.

[Are the cytostatic drugs and their metabolites, excreted by patients during chemotherapy, hazardous for the family environment?]. / Czy leki cytostatyczne i ich metabolity, wydalane przez pacjentów poddawanych chemioterapii, stanowia zagrozenie dla srodowiska rodzinnego?

In recent years the problem concerning adverse effects of excreted drugs and their active metabolites on other people and the environment has been found to be an important aspect of clinical pharmacology and environmental health. It is commonly known that antineoplastic drugs are hazardous to medical personnel who handle them, but cytostatics administered during ambulatory care are always transferred via the patient's organism to his home and hypothetically generate potential risk to other family members. The patient s home is a sub-set of the family environment where genetically determined predisposition to neoplastic disease could additionally appear. This could intensify the effect of exogenous factors responsible for carcinogenesis (e.g. cytostatics), and increase late consequences (e.g. mutations). To assess the risk the authors elaborated an algorithm for hazard identification and assessment of consequences of the hazard. Preliminary results indicated passage a/significant amounts of excreted cytostatics and their metabolites to the natural, hospital and also family environment. After excretion, mutagenic properties of these drugs were still observed. Chemical inactivation of the excreta of patients on chemotherapy completely eliminates or strongly reduces their mutagenicity. At the present time it is difficult to assess the total risk level of cytostalic drugs and their metabolites excreted by patients on chemotherapy, for their home environment. Risk identification based on dose-response and exposure assessment, will allow to determine the health, social and economic hazards and to establish standards of procedures with regard to the risk factor.

[Pharmacokinetics of methotrexate and therapeutic drug monitoring in children with osteosarcoma. Computer simulation using a pharmacokinetic model]. / Farmakokinetyka metotreksatu a monitorowanie terapii stezeniem leku u dzieci z miesakiem kosciopochodnym. Symulacja komputerowa z zastosowaniem modelu farmakokinetycznego.

The pharmacokinetics of methotrexate (MTX) and the therapeutic drug monitoring (TDM) in children treated-with high-dose of MTX (HD MTX) have been discussed. The pharmacokinetics of MTX was studied in 15 children (54 courses) with osteosarcoma, treated with HD MTX (8, 10 and 12 g/m2; 4 h i.v. infusion). Pharmacokinetic analysis was performed by standard non-compartmental methods and using two-compartment nonlinear model with coexistence of additional, parallel linear route of elimination from the central compartment. This proposed model can be used for computer simulation and prognosis of the serum-level curve course depending on the simulated dosage, enhanced diuresis and simulated kidney or liver insufficiency during the dose individualisation. The usage of the pharmacokinetic model for computer simulations may improve the understanding of MTX kinetics and can optimalise dosage regimens for the next cycles of chemotherapy.

[Monitoring high dose methotrexate therapy (HD MTX) in children with osteosarcoma and computer simulation using a pharmacokinetic model]. / Monitorowanie terapii wysokimi dawkami metotreksatu (HD MTX) u dzieci z miesakiem kosciopochodnym a symulacja komputerowa z zastosowaniem modelu farmakokinetycznego.

The pharmacokinetics of methotrexate (MTX) was studied in 15 children with osteosarcoma, treated (54 courses) with high-dose methotrexate (8, 10 i 12 g/m2; 4 h i.v. infusion). Pharmacokinetic analysis was performed by standard non-compartmental methods and using two-compartment nonlinear model with coexistence of additional, parallel linear route of elimination from central compartment. The model was used for computer simulation and prognosis of the serum-level curve course depending on the simulated dosage, enhanced diuresis and simulated kidney or liver insufficiency during the dose individualization. The usage of the pharmacokinetic model for computer simulations may improve understanding of the MTX kinetics and can optimise dosage regimens for the next cycles of chemotherapy.

Positive thyroid cancer scintigraphy using technetium-99m methoxyisobutylisonitrile.

The aim of the study was to evaluate the possibility of detecting thyroid cancer recurrences without the need for withdrawal of thyroid suppressive treatment. Upper-body or whole-body scintigraphy was performed in a group of 200 patients evaluated for differentiated thyroid cancers in 1993 and 1994 using technetium-99m sestamibi. Scans were performed 20-30min following i.v. administration of 500MBq of 99mTc-methoxyisobutylisonitrile (MIBI). Bone and lung metastases were detected with very high sensitivity and specificity, with a very high predictive value of negative results and a somewhat lower predictive value of positive results. The sensitivity and specificity of findings in the neck were lower but the predictive value of negative results was high. Whole-body scans with 99mTc-MIBI are a useful tool in the follow-up of patients with differentiated thyroid cancer, for the detection of distant metastatic lesions.

Positive thyroid cancer scintigraphy using 99Tcm-tetrofosmin (Myoview): a preliminary report.

99Tcm-tetrofosmin imaging was performed in 23 thyroid cancer patients and compared with whole-body 131I scans, neck ultrasonography and plasma thyroglobulin levels. Of 22 patients with differentiated thyroid cancer, 8 showed identical images on 131I scan and tetrofosmin; 1 patient with medullary cancer had identical images with 99Tcm-DMSA and 99Tcm-tetrofosmin, the findings being confirmed by sonography. The potential usefulness of 99Tcm-tetrofosmin imaging in the follow-up of thyroid cancers is discussed.

Osteocalcin in congenital adrenal hyperplasia.

Osteocalcin in the serum reflects bone turnover. It is known that prolonged therapy with glucocorticoids inhibits bone turnover. The aim of this study was to evaluate the osteocalcin level in children with congenital adrenal hyperplasia treated by glucocorticoids and mineralocorticoids and to assess the influence of 1,25(OH)2D3. The subjects were 75 children with congenital adrenal hyperplasia, aged 1-18 years, treated with glucocorticoids and mineralocorticoids in substitution doses from birth. These children demonstrated low levels of osteocalcin and alkaline phosphatase, whereas calcium and phosphate were in the normal ranges. Despite these abnormalities, no osteoporosis was detectable and a normal growth rate was confirmed, most probably because of higher levels of androgens; 17-OH progesterone averaged 11.8 nmol/l. After treatment with 1,25(OH)2D3, the osteocalcin levels increased, followed later by increases of alkaline phosphatase and bone isoenzyme.

[Development of various technical modifications in diagnostic sonography of the thyroid gland and their possible clinical applications]. / Vývoj ruzných technických modifikaci diagnosické sonografie stínté zlázy a moznosti jejich klinického vyuziti.

The authors evaluate twenty-five years application of ultrasound in the diagnosis of thyrroid disease focused on the technical development and closely associated possibilities of morphological and functional interpretations of sonographic findings. They discuss future perspectives of the use of ultrasound in thryology, in particular duplex sonography and coloured coded Doppler sonography. Attention is devoted to perspectives aimed aspiration biopsy under sonographic control and extension of its indications. They discuss the possible asset of further in this country so far not applied modifications of diagnostic sonography in thyrology, incl. the development of mathematical and statistical methods of evaluation of the echogenity and echotexture of thyroid tissue.

[Subclinical hypothyroidism]. / Subklinická hypotyreóza.

Subclinical hypothyroidism was detected in 5.7% of 853 patients referred for ambulatory examination to a department in Prague. In patients referred with a mild degree of subclinical hypothyroidism with an evaluated level of thyrotropic hormone in serum (TSH) no significant deviations of serum thyroxine and triiodothyronine (T4 and T3) were found nor different values of the Achilles tendon reflex time, as compared with patients with normal thyroid function. In case of a more marked grade of subclinical hypothyroidism with an elevated TSH level without stimulation the patients have on average significantly lower T4 vales, significantly longer Achilles tendon reflex times and preejection stage of left ventricular contraction, and of Rodbard's Q-Kd interval (Q-Kd) than euthyroid patients. The values are, however, still within the reference range for normal function and in individual cases cannot be decisive for establishment of the diagnosis. The authors discuss the differential diagnosis and views on treatment of this disease.

[The effect of fenoterol (partusisten) on cAMP and cGMP concentrations, acetylcholine esterase and choline acetyltransferase activities in rat placenta]. / Wplyw podawania fenoterolu (partusisten) na stezenie cAMP i cGMP, aktywnosci acetylotransferazy cholinowej i esterazy acetylocholinowej w lozysku szczura.

Several observations indicate a possible role of the placental cholinergic system in the modulation and maintenance of placental function and subsequently fetal growth and development. We have investigated the effect of Partusisten (1 mg/kg p.o., twice daily, since the 15th to the 20th day of gestation) on cAMP and cGMP concentrations, acetylcholine esterase and choline acetyltransferase activities in rat placenta. The obtained results show that Partusisten increased cAMP concentration and decreased cGMP concentration (see Tab. 1; Fig. 1, 2). Choline acetyltransferase activity was elevated (Tab. 2; Fig. 3) whereas Partusisten had no effect on acetylcholine esterase activity (see Tab. 2; Fig. 4). The results indicate disorders in placental cholinergic system after chronic Partusisten administration to pregnant rats. On the other hand, the marked increase in choline acetyltransferase activity suggested the high adaptability of placenta.

Sonography in the evaluation of treatment of differentiated thyroid cancer. First results in 158 patients.

Sonographic examination of soft tissues of the neck was used to search for recurrent thyroid cancer in 158 patients. Two hundred and thirty-six sonographic findings were evaluated. Specificity of the method, regardless of the type of recurrence, was 0.96, sensitivity 0.66, precision 0.81, predictive value of negative finding 0.72. This compares favorably with the results of examination by palpation (sensitivity 0.32 to 0.52, according to the type of recurrence), or with those of palpation combined with thyroglobulin estimation (sensitivity 0.50 to 0.60). Most important was the possibility of early detection of unpalpable recurrent lesions showing no radioiodine uptake, or relapses with low thyroglobulin production. Systematic evaluation of out-patients using sonography could lower the need for radioiodine scans that are necessarily connected with thyroid hormone therapy withdrawal and that are usually performed in in-patients.

[Diurnal fluctuations in plasma carbamazepine level in children with epilepsy]. / Dobowe wahania poziomów karbamazepiny w osoczu u dzieci z padaczka.

After determination of carbamazepine level in plasma by means of gas chromatography 23 profiles of 24-hour concentrations were plotted in children aged from 20 months to 15 years treated for epilepsy. In 12 of them monotherapy was given (Amizepin-Polfa in a mean daily dose of 18.7 mg/kg) while polytherapy was given to 11 children (mean daily dose was 21.1 mg/kg). Considerable fluctuations of the level of the drug were found in the plasma over 24 hours in various children, and individual differences after the administration of carbamazepine alone or with other drugs. The 24-hour fluctuations of total carbamazepine in the plasma and individual differences are due, probably, to pharmacokinetic factors due to physiological differences between patients and were correlated more to the age of the child than to the administered dose.

[Carbamazepine dosage and its blood serum level in children]. / Dawkowanie karbamazepiny a jej poziom w surowicy krwi u dzieci.

Evaluating in 62 children aged from 4 months to 14 years (mean age 3 years 7 months) the correlation between the carbamazepine dosage (carbamazepine was given as the only drug in 21 cases, and as one of several drugs in 41) the authors failed to find a simple correlation. Nevertheless, most children receiving the "proper" doses had therapeutic plasma carbamazepine levels. Moreover, it was found that carbamazepine dose increase over 25 mg/kg daily caused on further rise of its plasma level.

Analysis of the 1,4-benzodiazepines by methods based on hydrolysis.

The analytical applications of the hydrolysis of 1,4-benzodiazepines to the corresponding benzophenone derivatives are reviewed according to the analytical methods used for their final determination. The scope and limitations of the individual methods for the hydrolysis products are discussed: Colour reactions, photometry, fluorimetry, thin-layer chromatography, gas chromatography and high-performance liquid chromatography. Published data on the kinetic parameters and mechanisms are summarized in an attempt to explain the problems involved in exploiting this reaction for analytical applications.