Localization dependent sensitivity of cerebral Na,K-ATPase to irradiation induced oxidative imbalance in rats.

Na,K-ATPase represents the key enzyme maintaining the ionic gradient across plasma membrane. It was documented that in directly irradiated organs the activity of this enzyme is decreased. The aim of present study was to clarify the remote effect of irradiation in mediastinal area on the activity of the Na,K-ATPase in selected brain regions in rats. Ionizing radiation in single dose 25 Gy induced alterations in oxidative status of blood plasma. Irradiation also decreased the activity of the Na,K-ATPase in cerebral cortex. Measurements of kinetic properties of the enzyme dependently on the concentration of energy substrate ATP or cofactor Na+ indicated that the lowered enzyme activity is probably a consequence of decreased number of active molecules of the enzyme, as suggested by lowered Vmax values (by 13 - 14%). Immunoblot analysis revealed that this effect is connected namely to decreased presence of α2 and α3 subunits (by 25% and 30% respectively). Considering the current concepts about involvement of the malfunction of α2 α3 subunits in development of primary brain dysfunctions, it may be hypothesized that the lowered functionality of those subunits of Na,K-ATPase may represent a predisposition to neurodegenerative disorders after irradiation. The observed effect seems to be localization dependent as the enzyme in cerebellum resisted to irradiation.

Possibilities of the exposure reduction of hands during the preparation and application of radiopharmaceuticals.

BACKGROUND: The current routinely used methods of estimating the skin equivalent dose relies on the finger dosimetry which usually largely underestimates the real maximum exposure and thus appropriate correction factors have to be used. METHODS: The group under the investigation consisted of 10 workers preparing and 5 workers administering radiopharmaceuticals labelled with 18F. The monitoring was carried out using 12 pairs of thermoluminiscent dosimeters (TLDs) placed on each hand of the worker. A total of 46 measurements were completed. The maximum exposure of the skin of hands, defined in terms of the quantity of the personal dose equivalent Hp(0.07), was related to the unit activity of radiopharmaceutical with which the worker came into the contact during the measurement. RESULTS: The exposure of the hands of workers handling 18F-labelled radiopharmaceuticals showed significant inhomogeneity. Out of 15 workers, in 53 % of cases, the maximum skin exposure was observed on the tip of their index finger. It was estimated that in about 60 % of the cases (during the preparation and administration of radiopharmaceuticals), the exposure may exceed the 3/10 of the annual dose limit. Moreover, in 40 % of all cases, the exposure may even be higher than this dose limit. The established relevant correction factors reached the values up to 8 (as for preparations) and 13 (as for administrations). CONCLUSIONS: The study resulted in the establishment of the appropriate correction factors and in the recommendations of procedures aimed at the further reduction of the exposure of extremities (Tab. 3, Fig. 2, Ref. 17).

ASSESSMENT OF THE LOCAL EXPOSURE OF SKIN ON HANDS OF NUCLEAR MEDICINE WORKERS HANDLING 18F-LABELLED RADIOPHARMACEUTICALS: PRELIMINARY CZECH STUDY.

The article summarises some preliminary results of the assessment of the exposure of hands of workers manipulating 18F-labelled radiopharmaceuticals based on personal monitoring at two nuclear medicine clinics in the Czech Republic. The measurements were carried out using special thermoluminescence dosemeters the readings of which could be interpreted in terms of the personal dose equivalent Hp(0.07) approximating the equivalent dose to the skin at various locations on the surface of both hands. The results have shown that out of 21 workers monitored, ∼43 % (preparation and applications of radiopharmaceuticals) may reach an exposure equal to three-tenth of the annual dose limit to the skin. At the same time, it can also be concluded that in ∼10 % cases of workers, the relevant dose limit may be exceeded.

A simple physical phantom for an intercomparison exercise on 241Am activity determination in the skull.

A simple hemispherical phantom has been designed and prepared for the EURADOS intercomparison exercise on (241)Am activity determination in the skull (2011-13). The phantom consists of three parts that substitute bone and soft tissues. (241)Am is deposited on the surfaces of the bone-substituting part. The design and assumed composition of phantom parts are discussed. A preparation of the voxel representation of the phantom is described. The spectrum of a real measurement of the physical phantom agrees well with the simulation. The physical phantom, and its voxel representation, is provided to the participants of the intercomparison exercise.

Effects of γ-irradiation on Na,K-ATPase in cardiac sarcolemma.

Previous studies showed that adverse effect of ionizing radiation on the cardiovascular system is beside other factors mostly mediated by reactive oxygen and nitrogen species, which deplete antioxidant stores. One of the structures highly sensitive to radicals is the Na,K-ATPase the main system responsible for extrusion of superfluous Na(+) out of the cell which utilizes the energy derived from ATP. The aim of present study was the investigation of functional properties of cardiac Na,K-ATPase in 20-week-old male rats 6 weeks after γ-irradiation by a dose 25 Gy (IR). Irradiation induced decrease of systolic blood pressure from 133 in controls to 85 mmHg in IR group together with hypertrophy of right ventricle (RV) and hypotrophy of left ventricle (LV). When activating the cardiac Na,K-ATPase with substrate, its activity was lower in IR in the whole concentration range of ATP. Evaluation of kinetic parameters revealed a decrease of the maximum velocity (V max) by 40 % with no changes in the value of Michaelis-Menten constant (K m). During activation with Na(+), we observed a decrease of the enzyme activity in hearts from IR at all tested Na(+) concentrations. The value of V max decreased by 38 %, and the concentration of Na(+) that gives half maximal reaction velocity (K Na) increased by 62 %. This impairment in the affinity of the Na(+)-binding site together with decreased number of active Na,K-ATPase molecules, as indicated by lowered V max values, are probably responsible for the deteriorated efflux of the excessive Na(+) from the intracellular space in hearts of irradiated rats.

Extremity exposure in nuclear medicine: preliminary results of a European study.

The Work Package 4 of the ORAMED project, a collaborative project (2008-11) supported by the European Commission within its seventh Framework Programme, is concerned with the optimisation of the extremity dosimetry of medical staff in nuclear medicine. To evaluate the extremity doses and dose distributions across the hands of medical staff working in nuclear medicine departments, an extensive measurement programme has been started in 32 nuclear medicine departments in Europe. This was done using a standard protocol recording all relevant information for radiation exposure, i.e. radiation protection devices and tools. This study shows the preliminary results obtained for this measurement campaign. For diagnostic purposes, the two most-used radionuclides were considered: (99m)Tc and (18)F. For therapeutic treatments, Zevalin(®) and DOTATOC (both labelled with (90)Y) were chosen. Large variations of doses were observed across the hands depending on different parameters. Furthermore, this study highlights the importance of the positioning of the extremity dosemeter for a correct estimate of the maximum skin doses.

N-Methyl-D-aspartate receptor antagonism decreases motility and inflammatory activation in the early phase of acute experimental colitis in the rat.

BACKGROUND: Inflammatory bowel diseases are accompanied by severe motility disorders. The aim of our study was to investigate whether the blockade of peripheral N-methyl-D-aspartate (NMDA)-sensitive glutamate receptors (NMDA-Rs) alters motility changes in chemically induced acute colitis and how this modulation is accomplished. METHODS: The inflammatory and motility changes in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis were studied in anaesthetized Wistar rats following treatment with the natural NMDA-R antagonist kynurenic acid (KynA) or SZR-72, a blood-brain barrier-permeable synthetic KynA analogue. The macrohaemodynamics, serosal microcirculation (visualized by intravital videomicroscopy), plasma levels of tumour necrosis factor alpha (TNF-alpha), inflammatory enzyme activities (xanthine oxidoreductase (XOR), myeloperoxidase (MPO) and nitric oxide synthase (NOS)), and colonic motility (with a strain-gauge technique) were evaluated 17 h after colitis induction and compared with the control conditions. KEY RESULTS: The TNBS enema induced a systemic hyperdynamic circulatory reaction, increased the serosal capillary blood flow, significantly elevated the mucosal XOR, MPO and NOS activities and augmented the colonic motility relative to the controls. The NMDA-R antagonist treatment with KynA or SZR-72 significantly reduced the XOR, NOS and MPO activities, decreased the motility and increased the tone of the colon. CONCLUSIONS & INFERENCES: These data demonstrate a potential modulatory mechanism of NMDA-R in altered colonic motility in TNBS colitis. Inhibition of the enteric NMDA-Rs may provide a therapeutic option via which to influence intestinal hypermotility, microcirculatory changes and inflammatory activation simultaneously.

Role of antibody to lipopolysaccharide in protection against low- and high-virulence strains of Francisella tularensis.

Mice immunised with lipopolysaccharide (LPS) from Francisella tularensis were protected against challenge with the live vaccine strain (LVS). However, when similarly immunised mice were challenged using the fully virulent F. tularensis strain Schu4, only an increase in the time to death was observed. Passive transfer of serum from LPS-immunised mice to naive mice afforded protection against F. tularensis LVS. LPS-immunised mice depleted of either CD4+ or CD8+ T-cells survived a F. tularensis LVS challenge although the rate of clearance of bacteria from the spleen was significantly reduced in the CD8+ depleted group. LPS-immunised mice boosted with F. tularensis LVS were re-challenged with F. tularensis Schu4. This cohort was significantly protected (LD(50) increased from <1 to >1000 CFU). However, passive transfer of serum did not confer protection and mice depleted of CD4+ or CD8+ T-cells did not survive.

[Radial forearm and fibula free flap reconstruction after radical resection of head and neck malignancies] / Alkari és fibula értengelyû szabadlebenyek alkalmazásával végzett tapasztalataink a fej-nyaki régióban.

The incidence of head and neck cancer has been rapidly increasing in Hungary during the last decade. Most of these tumors are discovered in advanced stage, consequently, surgical removal of the tumor results in large complex defects in the soft tisses and bone elements of the face and neck. For optimal anatomical and functional reconstruction we perform free flap transfer in increasing number of cases. Between December 1993 and March 2001 in the Head and Neck Surgery Department of the National Institute of Oncology the defects after resection of head and neck tumors were reconstructed with free flaps in 85 cases. Radial forearm flap in 64 cases, fibula osteoseptocutaneous flap in 14 cases were used. In 87% of the patients the postoperative period was uneventful, the surgical complications were not more numerous than following traditional reconstructions. The average duration of operations became shorter by 2.5 hours during the last two years than before. In most of the cases we achieved good functional and esthetic results. The quality of life of the patients was excellent in 14%, almost normal in 73% and bad with serious problems of social life in 13%. It is surprising that there was no significant difference between the survival of neck node positive and negative patients. In our practice the replacement of large defects in the head and neck region with free flaps is a reliable and useful method for reconstruction.

[Neoadjuvant chemotherapy in head and neck cancer] / Neoadjuváns kemoterápia fej-nyaki laphámrákban.

BACKGROUND: Neoadjuvant chemotherapy has an increasing role in multimodality treatment of advanced head and neck cancer. In this paper we summarize our first results with this treatment. METHOD: Thirty-five, previously untreated, mostly inoperable head and neck cancer patients were given two cycles of Cisplatin and 5FU chemotherapy. We continued the therapy only in case of regression until four cycles, then the patients received surgical and/or radiotherapy according to their status. After the treatment patients' status was regularly evaluated. RESULTS: We detected 4 complete and 20 partial responses after the chemotherapy. Three patients became eligible for a radical operation. At this moment 10 patients are free of tumor, 8 patients died in consequence of the tumor, we have no data in 3 cases, 3 patients are given palliative therapy because of progression, 4 patients are receiving radiotherapy and 7 patients with partial response are candidates for further active oncotherapy. CONCLUSIONS: Although the number of the patients we treated is too small for a statistical analysis, our results are similar to the conclusion of the large randomized studies: after neoadjuvant chemotherapy of advanced head and neck cancer partial response can improve the result of surgical or radiological treatment. Neoadjuvant chemotherapy does not improve survival in advanced head and neck cancer, but it is of great importance because of better quality of life of patients, especially those who had organ preserving therapy.

Serum beta-hydroxybutyrate measurement in patients with uncontrolled diabetes mellitus.

OBJECTIVE: To assess whether routinely measuring serum beta-hydroxybutyrate (beta-OHB) concentration might help judge the severity of or assist in treating patients with suspected ketoacidosis. METHODS: Serum beta-OHB level was estimated by a standard enzymatic method in 64 episodes in adults admitted to a municipal hospital. Of the 85 specimens analyzed, 60 were taken before treatment from a nearly consecutive group of diabetic patients with ketosis, 21 were follow-up specimens, and 4 were from nondiabetic patients with ketosis. RESULTS: In the 85 specimens, the correlation between serum carbon dioxide and beta-OHB levels was -0.69, and that between anion gap and beta-OHB level was 0.75. For just the initial specimens, the respective correlation coefficients were -0.60 and 0.52. CONCLUSIONS: The correlations between serum beta-OHB and carbon dioxide levels and the anion gap were close, but not sufficiently so for the beta-OHB measurements to be routinely useful alone to assess the severity of the ketoacidosis. Full laboratory assessment of the severity and characteristics of ketoacidosis also requires knowledge of serum carbon dioxide level, anion gap, often blood pH, and ideally serum acetoacetate and lactate concentrations as well as serum beta-OHB concentration.

The efficacy of ciprofloxacin and doxycycline against experimental tularaemia.

The efficacy of doxycycline and ciprofloxacin against an experimental tularaemia infection was assessed by comparing the median lethal dose (MLD) of Francisella tularensis Schu4 biotype A strain given intraperitoneally to antibiotic-treated and untreated mice. In untreated Porton outbred mice this was <1 cfu. Ciprofloxacin and doxycycline given at 40 mg/kg bd, initiated 48 h before infection and continued for 5 days after infection, afforded protection against intraperitoneal challenges of 3.7 x 10(6) cfu and 6.0 x 10(6) cfu, respectively. Protection was reduced when both antibiotics were given over a similar period at a lower dose regimen (20 mg/kg bd) to 8.8 x 10(5) cfu and 3.5 x 10(2) cfu, respectively. The greater reduction in protection offered by doxycycline was a reflection of the higher in-vitro MIC. Protection also decreased when the antibiotics were initiated 24 h after challenge. The MLD was 3.2 x 10(5) cfu and 1.6 x 10(6) cfu for ciprofloxacin and doxycycline respectively given at 40 mg/kg bd and was reduced further using the lower dose regimen. Overall, 90% of the deaths occurred following the withdrawal of antibiotic, irrespective of the antibiotic dose or type. It was possible to prevent this relapse by extending the antibiotic administration to 10 days after challenge. Ciprofloxacin and doxycycline may be useful for treating tularaemia, although the possibility of relapse should be considered.

Body potassium content and radiation dose from 40K to the Slovak population.

A group of 219 subjects of Slovak adults from both sexes were studied for potassium body content by measuring the whole body activity of naturally occurring 40K using a whole body counter. The average body potassium value is 1.68 +/- 0.33 g kg(-1) body weight for males and 1.60 +/- 0.30 g kg(-1) for females. For both sexes the average body content of K was 1.62 +/- 0.30 g kg(-1). The concentration of potassium varies inversely with age. The specific activity of 40K varies inversely with slenderness. The total body potassium varies directly with body-build index for males, while its value is essentially constant for young females and tends to decrease with body-build index for old females. The average annual dose from 40K is 150 +/- 30 microGy for males and 140 +/- 30 microGy for females. For both sexes the average annual dose is 142 +/- 30 microGy. Both total potassium body content and annual dose from 40K for older subjects are below the values reported by the UNSCEAR.

Flow diagrams for the diagnosis of acid-base disorders.

This article discusses flow diagrams and tables intended to provide a systematic approach to the rapid laboratory differential diagnosis of acid-base disorders in the emergency department.

Algorithms for diagnosing some electrolyte disorders.

The differential diagnosis of electrolyte disorders has traditionally been framed in terms of pathophysiology, and analysis of clinical problems has usually proceeded in the same way. However, easier access to rapid-response laboratory analysis has prompted physicians who encounter patients with serious electrolyte abnormalities to try to establish the cause by quickly obtaining further simple tests. In that vein, this article and the algorithms that are presented are intended to assist the preliminary laboratory differential diagnosis of low and high serum levels of sodium, potassium, and calcium.

In-situ measurements of 137Cs in soil by unfolding method.

An improved in-situ spectrometry measurement of 137Cs concentration in soil is introduced. The method uses the information contained in the pulse spectrum in order to forego the need for soil sampling. The approach is based on the unfolding of responses of a collimated and uncollimated HPGe detector to primary 0.662 MeV photons and to photons scattered forward in the soil. The calibration of the in situ equipment has been performed by Monte Carlo calculations and by experiments. For unfolding of experimental detector responses the code SAND II has been found reliable and capable of calculating distribution of 137Cs in soil profile with adequate accuracy for environmental monitoring purposes. The analysis of the spectra indicates that 137Cs concentration in soil 10 y after Chernobyl accident would be measurable using a middle HPGe detector (20-30% relative efficiency) and a counting time on the order of 1 h. Even with smaller detectors, 137Cs concentrations of 5 kBq m(-2) are measurable, and the depth distribution of 137Cs activities above 10 kBq m(-2) in the soil can be estimated by the presented method when a counting time on the order of 3 h is used.

Health risk behaviors among California college students.

Health risk behaviors among students attending 4-year colleges in California were examined. The Youth Risk Behavior Survey for College Students was administered in a two-stage (29 universities, 5,652 students) random sample. All campuses and 3,810 (69%) students participated in the survey. In the 30 days preceding the survey, 36.7% of the students had binged at least once while drinking; 25.3% had driven after consuming alcohol; 32% had ridden in a car with someone who had been drinking; 17.6% had used marijuana; and 6% had carried a knife, gun, or club. More than half of the students who were sexually active and not married or living with a primary partner had not used a condom the last time they had sexual intercourse. Only 5% of regular bicycle riders always wore a helmet. Fewer than half (44%) reported aerobic physical activity on 3 or more of the preceding 7 days. The results of this study indicate a substantial amount of serious, risky health behaviors among California college students.

Binge drinking among college students: a comparison of California with other states.

California college students (1,864 students from 15 colleges) were compared with students who participated in the Harvard School of Public Health College Alcohol Study, which surveyed 17,592 students in 140 colleges nationwide. California college students, in comparison with the remainder of the nation, were less frequent drinkers; less frequent binge drinkers; exhibited fewer personal problems and risks associated with heavy episodic drinking, including drinking and driving; and reported fewer "secondhand" effects of binge drinking, such as being physically assaulted or experiencing an unwanted sexual advance. Many of these differences appear to be related to the California college students' being older, more likely to be married, and less likely to live on campus than those in the Harvard study. The findings suggest that, in developing programs tailored to local needs, there is significant value in augmenting national surveillance of college student health risk behaviors with the development of regional, state, and local surveillance systems.