Half-time Values Research Articles

Exercise capacity and oxygen recovery half times of skeletal muscle in patients with fibromyalgia

It is known that increased muscle fatigability and exercise intolerance is a major symptom of fibromyalgia (FM) [1]. Although many models have been proposed, the patho-physiology of exercise intolerance in FM remains unclear. Up to now, muscle fatigue and exercise tolerance can be explained by numerous central and peripheral mechanisms [1]; however, the exact patho-physiological role of the microvascular involvement in FM is still unclear. As a peripheral mechanism, there are few reports on abnormalities of the microcirculation in patients with fibromyalgia. Continuous wave near-infrared spectroscopy (NIRS) technology is based on the fact that light in the wavelength range 650–950 nm is weakly absorbed by tissues and signal intensity changed mainly due to hemoglobin. Since light passing through the large vessels is mostly absorbed, light that reaches the detector comes mainly from small blood vessels (arterioles, capillaries and venules) [2]. Thus, it gives dynamic balance information between oxygen supply and consumption of skeletal muscles. The objective of the present study was to evaluate association with exercise intolerance and oxygen recovery half times of skeletal muscle in patients with FM. Thirty-three female subjects (18 consecutive female patients with FM), aged between 21 and 36 years, were investigated. All subjects were fully informed of any risks and discomforts associated with the experiments before giving their informed written consent to participate with ethical approved. All have taken examination by near-infrared spectroscopy and cardiopulmonary exercise testing. In the experiment protocol, brachial ischemia was used for detecting muscular oxygen kinetics by NIRS method before cardiopulmonary exercise testing. A continuous wave NIRS device was used (Niroxcope 201, Biophotonics Lab) and the probe containing multiple source-detectors was placed on the subjects’ lower half of left forearm and arterial blood flow is restricted by placing a tourniquet on the upper arm at a pressure of 250 mmHg after a 5 min baseline measurement, and then post-ischemic measurement was taken. In both rest and post-ischemic traces, change of difference of oxyhemoglobin and deoxyhemoglobin concentrations between minimum point and maximum point was taken as the full range and time to reach half of the 95% of the full range was calculated as half-time value (t1/2) [2]. Then, all participants underwent a standard Bruce multistage maximal treadmill protocol with metabolic measurements. All exercise testings were discontinued due to fatigue. Peak oxygen conM. Dinler AE C. Aksoy AE A. Oncel AE E. Berker Department of Physical Medicine and Rehabilitation, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

Halftime for repair of sublethal damage in normal bladder and rectum: an analysis of clinical data from cervix brachytherapy

The halftime for repair of sub-lethal damage is an important radiobiological parameter in analysing radiation responses and in designing new treatments involving different dose rates. This work is to resolve an inconsistency existing in the repair halftime for the bladder and rectum, two of the most dose limiting critical structures for pelvic irradiation. Both long (1.5–2 h) and short (0.3–1 h) repair halftimes have been reported previously. In this work, by reconciling clinical data from cervical brachytherapy of different dose rates and by introducing a sparing factor to consider the dose sparing occurring for critical structures, we have estimated that the most likely value of the repair halftime for bladder and rectum is short, 0.2–0.4 h if assuming α/β = 2–4 Gy. The present analysis does not support the long repair halftimes reported previously for the bladder and rectum and for other normal structures.

Primary sclerosing cholangitis: Correlation of hepatobiliary scintigraphy with clinical and laboratory status

The aim of this study was to determine whether hepatobiliary scintigraphy using (99m)technetium based di-isopropryl-imino-diacetic acid correlated to clinical or laboratory status of patients with primary sclerosing cholangitis (PSC). We carried out a retrospective case-control study involving 15 patients with proven PSC. Fifty-seven hepatobiliary scintigraphic studies were reviewed by consensus of two experienced observers using a semiquantitative scheme to score liver size and degree of radiopharmaceutical uptake, intrahepatic or extrahepatic biliary stasis, segmental liver clearance half-times and gall bladder visualization. The results were compared with age; disease duration; weight loss; serum bilirubin, alkaline phosphatase and albumin levels; antipyrine clearance; number of biliary stents and episodes of cholangitis and history of transplantation. Sixteen age-matched and sex-matched individuals with PSC, who did not undergo hepatobiliary scans, were selected for comparison. Among the scintigraphic variables, right lateral and superior liver clearance half-time values showed a significant linear correlation with disease duration and serum alkaline phosphatase levels (P < 0.05) but not with other clinical or biochemical indices. Other scintigraphic variables showed no correlation. An abnormal, hepatobiliary scan liver clearance half-time in patients with PSC correlates to disease duration and increased serum alkaline phosphatase levels, and this variable may be used to identify some subjects with more advanced disease.

Metabolism of perfused pig intercostal muscles evaluated by 31P‐magnetic resonance spectroscopy

This study presents a perfused preparation for evaluation of metabolism in pig intercostal muscle in vitro. Preserved vessels and nerves to an intercostal segment including two adjacent ribs allowed for tissue perfusion and electrical stimulation with measurement of contraction force, oxygen consumption and 31P-magnetic resonance spectroscopy (31P-MRS). When perfused at rest with Krebs-Ringer buffer, the preparation maintained physiological levels of phosphocreatine (PCr), inorganic phosphate (Pi), ATP and pH at a stable oxygen consumption of 0.51 +/- 0.01 micromol min(-1) g(-1) for more than 2 h. Tonic stimulation of the nerve caused anaerobic energy consumption as PCr and pH decreased, and both variables recovered after the contraction with half-time values of approximately 7 min. Force increased to 0.040 N g(-1) (range, 0.031-0.103 N g(-1)) and it gradually decreased by about 70% during the subsequent 5 min of stimulation. The calculated free ADP concentration increased from 7.4 +/- 2.1 nmol g(-1) at rest to 28 +/- 12 nmol g(-1) (mean +/- s.d.) by the end of the stimulation. Thus anaerobic ATP turnover was zero at rest, 6.1 +/- 2 micromol min(-1) g(-1) during the first minute of stimulation and 3.5 +/- 0.5 micromol min(-1) g(-1) during the two last minutes, corresponding to the drop in force. When the preparation was left unperfused, anaerobic ATP turnover averaged 0.40 +/- 0.15 micromol min(-1) g(-1) for the first 10 min. The preparation can also be applied to human intercostal muscles, as demonstrated in one preliminary experiment. The results demonstrate a stable and functional in vitro preparation of intact perfused intercostal muscles in the pig.

A micellar model system for the role of zeaxanthin in the non-photochemical quenching process of photosynthesis—chlorophyll fluorescence quenching by the xanthophylls

To get an insight to the mechanism of the zeaxanthin-dependent non-photochemical quenching in photosystem II of photosynthesis, we probed the interaction of some xanthophylls with excited chlorophyll-a by trapping both pigments in micelles of triton X-100. Optimal distribution of pigments among micelles was obtained by proper control of the micelle concentration, using formamide in the reaction mixture, which varies the micellar aggregation number over three orders of magnitude. The optimal reaction mixture was obtained around 40% (v/v) formamide in 0.2–0.4% (v/v) triton X-100 in water. Zeaxanthin in the micellar solution exhibited initially absorption and circular dichroism spectral features corresponding to a J-type aggregate. The spectrum was transformed over time (half-time values vary—an average characteristic figure is roughly 20 min) to give features representing an H-type aggregate. The isosbestic point in the series of spectral curves favors the supposition of a rather simple reaction between two pure J and H-types dimeric species. Violaxanthin exhibited immediately stable spectral features corresponding to a mixture of J-type and more predominately H-type dimers. Lutein, neoxanthin and β-carotene did not show any aggregated spectral forms in micelles. The spectral features in micelles were compared to spectra in aqueous acetone, where the assignment to various aggregated types was established previously. The specific tendency of zeaxanthin to form the J-type dimer (or aggregate) could be important for its function in photosynthesis. The abilities of five carotenoids (zeaxanthin, violaxanthin, lutein, neoxanthin and β-carotene) to quench chlorophyll-a fluorescence were compared. Zeaxanthin, in its two micellar dimeric forms, and β-carotene were comparable good quenchers of chlorophyll-a fluorescence. Violaxanthin was a much weaker quencher, if at all. Lutein and neoxanthin rather enhanced the fluorescence. The implications to non-photochemical quenching process in photosynthesis are discussed.

Radiation‐induced DNA damage and repair in peripheral blood mononuclear cells from Nijmegen breakage syndrome patients and carriers assessed by the Comet assay

Nijmegen breakage syndrome (NBS) patients and carriers are predisposed to malignancy and are often treated with X-irradiation. In the present study, the single-cell gel electrophoresis (Comet) assay was used to examine radiation-induced DNA damage and repair in peripheral blood mononuclear cells from NBS patients (n=13) and carriers (n=36) of six unrelated families. Cells from apparently healthy donors (n=10) and from breast cancer patients with normal clinical radiosensitivity (n=10) served as controls. Cells were irradiated with 5 Gy of X-rays and assayed for initial DNA damage and for residual DNA damage after 40 min of repair; the kinetics of DNA repair also was estimated. In addition, the nuclear area of unirradiated cells was extracted from the Comet data. The initial radiation-induced DNA fragmentation indicated that cells from members of two out of six NBS families were significantly more sensitive to X-irradiation than cells from the controls. Cells from four NBS families had longer DNA repair half-time values, while cells from five NBS families had significantly increased residual DNA damage following repair. The mean nuclear area of unirradiated cells processed in the Comet assay was 1.3-fold higher in cells from all NBS families than in the controls (P<0.05). Notably, the Comet assay parameters (initial and residual DNA damage and the repair kinetics) of irradiated NBS cells predicted the carrier status of the majority (86%) of blindly tested individuals. The prediction of NBS status was higher if the nuclear area of unirradiated cells was used as the endpoint. The results of this study suggest that the impaired radiation response of NBS cells should be taken into account if radiotherapy of NBS patients and carriers is required.

Management of 131I therapy for thyroid cancer: cumulative dose from in-patients, discharge planning and personnel requirements

To provide a comprehensive overview with regard to the hospitalization/discharge planning and nursing staff requirements for the management of patients treated with radioiodine for differentiated thyroid carcinoma. A statistical analysis of the fast clearance phase of 131I was performed in 265 hospitalized patients treated after total thyroidectomy with fixed doses ranging from 2590 to 9250 MBq. Two hundred and twenty-five cases were post-surgical ablation treatments and 40 cases were follow-up treatments. The 131I clearance was studied during hospitalization of 2-4 days. No clearance differences were found between the two groups. The median value of the biological half-time (T1/2bio) was 0.65 days, with a variability range of 0.30-2.03 days. A statistical model for the distribution of T(1/2bio) was reported. Some patients on maintenance haemodialysis were also studied, with T(1/2bio) values ranging from 1.6 to 2.6 days. The weekly cumulative dose to personnel from external exposure, corresponding to the 95th percentile, ranged from 0.1 mSv per GBq of administered activity (mSv x GBq(-1)) with a totally ambulant patient to 5.4 mSv . GBq with a totally helpless patient. With patients on maintenance haemodialysis, these values could increase from 1.2 to 1.7 times. The cumulative dose to close relatives was also estimated. The hospitalization times associated with 75% and 95% probabilities of patient discharge were calculated by varying the residual activity limit from 100 to 800 MBq. Finally, using the median T(1/2bio), personnel requirements were evaluated. With totally ambulant and semi-ambulant patients, about 0.5 and 1.0 personnel units per GBq of weekly administered activity were needed so as not to exceed an annual planning dose of 6 mSv per year. The treatment of patients with higher degrees of dependency was impractical. On the basis of statistical analysis, a better organization of in-patient treatment may be obtained, as well as more accurate preliminary evaluations of the cumulative doses to nursing staff and attending personnel, for the management of patients treated with radioiodine for differentiated thyroid carcinoma.

Evaluation of Nasal Mucociliary Functions with Rhinoscintigraphy in Coal Workers’ Pneumoconiosis

Objective: To compare nasal mucociliary clearance (NMC) functions in coal workers with pneumoconiosis, coal workers without pneumoconiosis and healthy controls by using technetium-99m-labeled macroaggregated albumin rhinoscintigraphy. Methods: Sixty-five of the 86 coal workers were clinically documented as suffering from coal workers’ pneumoconiosis (CWP group). CWP workers were divided into two groups according to smoking status: 44 smokers (CWP-S) and 21 nonsmokers (CWP-NS). Twenty-one workers without pneumoconiosis (NCWP group) were similarly divided into two groups: 12 smokers (NCWP-S) and 9 nonsmokers (NCWP-NS). Thirty-three healthy male volunteers were selected for the control group [15 smokers (control-S), 18 nonsmokers (control-NS)]. The half-time (t_½) value for the clearance of the radiopharmaceutical was calculated for each patient. Results: Mean t_½ values for CWP-S, CWP-NS, NCWP-S, NCWP-NS, control-S and control-NS were 25.10 ± 7.75, 10.97 ± 3.24, 14.68 ± 4.98, 9.17 ± 3.71, 19.15 ± 5.04 and 15.08 ± 5.11, respectively (p < 0.001, Kruskal-Wallis variance analysis). Further, mean t_½ values of smokers versus nonsmokers in CWP, NCWP and control groups were compared, and it was found that although smoking prolonged nasal transport time in all three groups, the difference was significant only in the CWP group (p < 0.001, p < 0.023 and p < 0.027, respectively, Bonferroni-adjusted Mann-Whitney test). Conclusion: Our findings demonstrated a synergistic detrimental effect of smoking with coal dust exposure on nasal transport time.

Non-isothermal crystallization kinetics of silane crosslinked polyethylene

The non-isothermal crystallization kinetics of silane crosslinked polyethylene (SXPE) and dicumyl peroxide (DCP) modified polyethylene (DMPE) were studied by differential scanning calorimetry at different cooling rates. Three methods, namely, the Avrami, the Ozawa, and the Mo, were applied to describe the crystallization process of virgin LLDPE, DMPE and SXPE under non-isothermal conditions. The values of half-time of crystallization t 1/2, and the parameter Z c in the Avrami method which characterize the kinetics of non-isothermal crystallization, show that the crystallization rates of virgin LLDPE and DMPE are faster than that of SXPE at the same cooling rate, and crystallization rates of all samples increase as the cooling rate increases. The Ozawa model is also suitable to describe the process of the non-isothermal crystallization kinetics of all samples. In the Mo method, it has been found that the F( T) values of virgin LLDPE and DMPE are lower than that of SXPE, meaning that the crystallization rate of virgin LLDPE and DMPE is faster than that of SXPE.

Low-dose-rate brachytherapy is superior to high-dose-rate brachytherapy for bladder cancer

Purpose To determine the efficacy and safety of a high-dose-rate (HDR) brachytherapy schedule in the treatment of bladder cancer and to investigate the impact of different values of repair half-times and α/β ratios on the design of the HDR schedule. Methods and materials Between 2000 and 2002, 40 patients with T1G3 and T2 bladder carcinoma were treated with 30 Gy external beam radiotherapy followed by interstitial HDR brachytherapy to a total dose of 32 Gy in 10 sessions of 3.2-Gy fractions in two fractions daily with a 6-h interfraction interval. The local control rate and toxicity were compared with a historical group of 108 patients treated with 30 Gy external beam radiotherapy followed by 40-Gy interstitial low-dose-rate (LDR) brachytherapy. The HDR schedule was designed to be biologically equivalent to the previously used LDR schedule with the linear-quadratic model, including incomplete mono-exponential repair. Results The local control rate at 2 years was 72% for HDR vs. 88% for LDR brachytherapy ( p = 0.04). In the HDR group, 5 of 30 evaluable patients encountered serious late toxicity: 4 patients developed a contracted bladder with inadequate capacity (<100 mL), and 1 patient required cystectomy because of a painful ulcer at the implant site. In the LDR group, only 2 of 84 assessable patients developed serious late toxicity. One patient developed a persisting vesicocutaneous fistula and the other a urethral stricture due to fibrosis. The difference in observed late toxicity for HDR vs. LDR was statistically significant ( p = 0.005). The increased late toxicity with the HDR schedule compared with the LDR schedule suggests a short repair half-time of 0.5–1 h for late-responding normal bladder tissue. Conclusion Local control of HDR brachytherapy for bladder cancer was disappointing and late toxicity unexpectedly high. The increase in late toxicity suggested a short repair half-time of 0.5–1 h for late-responding normal bladder tissue, which would not support HDR brachytherapy in the treatment of bladder cancer. The analysis demonstrated that the calculation of equivalent HDR schedules on the basis of the LDR schedules used in clinical practice might be hazardous.

PE/Org-MMT nanocomposites

The non-isothermal crystallization kinetics of polyethylene (PE), PE/organic-montmorillonite (Org-MMT) composites were investigated by differential scanning calorimetry (DSC) with various cooling rates. The Avrami analysis modified by Jeziorny and a method developed by Mo were employed to describe the non-isothermal crystallization process of these samples very well. The difference in the exponent n between PE and PE/Org-MMT nanocomposites, indicated that non-isothermal kinetic crystallization corresponded to tridimensional growth with heterogeneous nucleation. The values of half-time, Zc and F(T) showed that the crystallization rate increased with the increasing of cooling rates for PE and PE/Org-MMT composites, but the crystallization rate of PE/Org-MMT composite was faster than that of PE at a given cooling rate. The method developed by Ozawa did not describe the non-isothermal crystallization process of PE very well. Moreover, the method proposed by Kissinger was used to evaluate the activation energy of the mentioned samples. The results showed that the activation energy of PE/Org-MMT was greatly larger than that of PE.

Cesium-134 and strontium-85 in strawberry plants following wet aerial deposition.

The understanding of the processes that control the behavior of radionuclides in crops can support policymakers to take actions to protect the environment and safeguard human health. Data concerning the behavior of radionuclides in fruits are limited. Strawberry (Fragaria x ananassa Duchesne) plants were contaminated on the aboveground part by sprinkling an aqueous solution of 134Cs and 85Sr at three growing stages: predormancy, anthesis, and beginning of ripening. Intercepted activity was more affected by the posture and physical orientation of leaves rather than by leaf area or biomass. Fruit interception ranges from 0.2 to 1.2% of the sprinkled activity. Translocation coefficients from leaf to fruit are on the order of 10(-4) for 134Cs and 10(-5) for 85Sr. Translocation reaches its highest intensity between anthesis and ripening. If deposition occurs when plants are bearing fruits, the fruit activity will be affected by the activity initially deposited on the fruit surfaces. This is important for 85Sr as it is not translocated in the phloem. The loss of the dead leaves at the resumption of growth causes high plant decontamination, but a fraction of both radionuclides remains in the storage organs, roots, and shoots, which is retranslocated to fruits in the following spring. The values of the environmental half-time, t(w), after deposition at predormancy are 114 d for 134Cs and 109 d for 85Sr. Cesium-134 tends to be allocated to fruits, while 85Sr remains in leaves and crowns. Translocation of radionuclides to roots results in soil contamination.

Normal values for Doppler echocardiographic assessment of heart valve prostheses

Assessment of normal and abnormal function of heart valve prostheses remains challenging. Doppler echocardiography has been shown to allow hemodynamic evaluation in various clinical settings and has become the most widely used tool to assess prosthetic valve function. Prosthetic valves, even when they function normally, are to some degree obstructive to the blood flow. The normal values of gradients, pressure half-time, and effective orifice area depend on valve type and valve size. Doppler assessment of prosthetic valve function, thus, requires specification of valve type and valve size, and knowledge of the normal values. This study provides an updated overview on the available data of normal values to facilitate adequate interpretation of Doppler data.

Pressure effects on the GTPase activity of brain membrane G proteins of deep-living marine fishes

In marine fishes, heterotrimeric guanyl nucleotide binding proteins (G proteins), which couple cell surface membrane receptors to their effector elements, are sensitive to hydrostatic pressure. The intrinsic high affinity GTPase activity of the α subunits of G proteins in three signaling systems coupled to adenylyl cyclase, the A 1 adenosine receptor, the muscarinic cholinergic receptor and the β-adrenergic receptor, was tested at pressures up to 340 atm. Brain membrane preparations from four members of the deep-sea teleost fish family Macrouridae were studied. Coryphaenoides armatus, C. filifer, C. rupestris and Macrourus berglax have depth distributions which together span 100–5810 m. Increased pressure inhibited basal GTPase activity only in M. berglax, which of the four species has the shallowest center of abundance. Increased hydrostatic pressure did not alter the response of GTPase activity to the β-adrenergic receptor agonist isoproterenol. Increased pressure decreased the stimulation of GTPase activity by the A 1 adenosine receptor agonist cyclopentyladenosine (CPA) in C. armatus and M. berglax, and by the muscarinic cholinergic receptor agonist carbamyl choline in C. armatus, C. filifer and M. berglax. Decreased agonist-stimulation of the GTPase activity at elevated pressure may result from pressure-induced changes in conformational states or inhibition of agonist binding. The binding of the non-hydrolyzable GTP analog guanosine 5′-[γ-thio]triphosphate (GTP[S]) in response to CPA was determined at 5 °C and atmospheric pressure. Six macrourid species and a morid were studied. The halftime ( t 1/2) values for GTP[S] binding, ranging from 20.8 to 40.9 min, are similar to values previously reported for two other cold-adapted fishes.

Preparation and crystallization behaviour of PP/PP-g-MAH/Org-MMT nanocomposite

The melt-direct intercalation method was employed to prepare polypropylene (PP)/maleic anhydride grafted polypropylene (PP-g-MAH)/organic-montmorillonite (Org-MMT), X-ray diffractometer was used to investigate the intercalation effect and crystallite size in composites and TEM micrograph to observe the dispersion of Org-MMT interlayers in polypropylene. The results showed that by introducing maleated polypropylene in PP/Org-MMT composite, macromolecule segments had intercalated into interlayer space of Org-MMT. As a result, Org-MMT interlayers were dispersed evenly in polypropylene and PP/PP-g-MAH/Org-MMT nanocomposite was synthesized. The crystallite size of nanocomposite perpendicular to the crystalline plane such as (0 4 0), (1 3 0), (1 1 1), (0 4 1) is smaller than that of pristine PP, which indicated that the crystallite size of PP in nanocomposite can be diminished by adding PP-g-MAH and Org-MMT in PP. Moreover, the nonisothermal crystallization kinetics of PP and PP/PP-g-MAH/Org-MMT nanocomposite was investigated by differential scanning calorimetry (DSC) with various cooling rates. The Avrami analysis modified by Jeziorny, Ozawa method and a method developed by Liu were employed to describe the nonisothermal crystallization process of these samples. The difference in the exponent n between PP and nanocomposite, indicated that nonisothermal kinetic crystallization corresponded to tridimensional growth with heterogeneous nucleation. The values of half-time, Z c, F( T) and K( T) showed that the crystallization rate of composites was faster than that of PP at a given cooling rate.

Time-resolved crystallization study of absorbable polymers by synchrotron small-angle X-ray scattering

Changes in the lamellar morphology that occurred during the quiescent isothermal crystallization of absorbable poly(p-dioxanone) (PDS) and PDS/poly(glycolide) block copolymer were studied by synchrotron small-angle X-ray scattering. Important morphological parameters such as the lamellar long period, the thicknesses of the crystal and amorphous phases, and the scattering invariant were estimated as a function of time, and trends observed over a wide range of experimental conditions are discussed. Thicker but more perfect lamellae were detected at higher crystallization temperatures. The breadth of the normalized semilog Lorentz-corrected intensity peak systematically decreased with increasing temperature. In addition, the values of the crystallization half-time and the Avrami exponent (n = 2.5), determined from the real-time changes in the lamellar development, showed superb agreement with the bulk crystallinity data generated from other experimental techniques, such as calorimetry and dielectric relaxation spectroscopy. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 39: 153–167, 2001

Modelling of continuous low dose rate and accelerated fractionated high dose rate irradiation treatments in a human glioma cell line

The Incomplete-Repair model of Thames in its original and in its two-repair processes forms is used to analyse continuous and fractionated irradiation of a glioma cell line treated in vitro. Furthermore, the Incomplete-Repair model is rederived based on the linear-quadratic model bearing a cubic term. Our results show a potentially enhanced but nonsignificantly improved fit to the data when comparing the cubic to the original form of this model. The repair half-time values showed a decrease, followed by an increase, as a function of small doses (< 1.5Gy) per fraction. This is observed using both the original and the cubic forms of the model. We propose this behaviour to be due to an induced resistance of the repair system followed by a saturation process. Two-repair processes were not seen directly due to the large scatter in the fast and the slow components of repair. Repair half-time values are estimated for various dose per fraction protocols using the original and extended forms of the Incomplete-Repair model. Two-repair processes that are consistent as a function of dose per fraction were not detectable in a glioma cell line treated in vitro.

Acute reaction parameters for human oropharyngeal mucosa

The purpose of this study was to determine the influence of changes in dose rate over the range 0.8-240 Gy/h on acute oropharyngeal mucosal reactions in human subjects, and to estimate the values of the important parameters that influence these reactions. Sixty-one patients requiring radiotherapy to palliate incurable head and neck cancer were treated on a telecaesium unit, using opposing lateral portals to total midline doses, varying between 30 and 42 Gy in 10 daily fractions over 2 weeks, at dose rates of 0.8, 1.8, 3.0 and 240 Gy/h according to a central composite study design. The severity and time course of reactions were charted at least twice weekly for each patient, using the EORTC/RTOG acute mucosal reaction grading system. Duration of reaction at each grade was observed to provide a more sensitive reflection of effect than the proportion of patients reaching any particular reaction grade. Analysis of duration by direct and indirect methods suggest alpha/beta ratios in the range 7-10 Gy and half-time (t1/2) values in the range 0.27-0.5 h, if mono-exponential repair kinetics are assumed. The t1/2 values are short and raise the question as to whether the repair kinetics of this tissue are well described by a mono-exponential function. Further prospective studies involving multiple daily fraction treatment regimes delivered at high dose rate, in which interfraction interval is deliberately varied, are needed to find out whether the parameters derived from this project are applicable to fractionated treatment courses at high dose rate.

In vivo turnover of 1,2-dipalmitoylphosphatidylcholine and sphingomyelin in rabbit erythrocytes

The in vivo turnover of both 1,2-dipalmitoylphosphatidylcholine (DPPC) and sphingomyelin (SM) in rabbit erythrocytes was studied. DPPC, either 14C-labelled in the fatty acyl chain at the 2-position of the glycerol moiety or 3H-labelled in the choline's methyl group, and [ N- methyl- 14C]SM (bovine) were introduced into the membrane of freshly isolated rabbit erythrocytes by using phospholipid transfer proteins. Thereafter, the labelled erythrocytes were reinjected into the bloodstream of the animal. Analysis of blood samples shows that both labels disappear from the circulating cells with the same rate, resulting in a half-time value of about 6.4–6.6 days. This result demonstrates that the loss of DPPC from the cells is due to transfer of intact molecules to the plasma and that a deacylation process is of no or minor importance as mechanism of renewal of DPPC. Labelled sphingomyelin, introduced into the rabbit erythrocyte membrane in a similar way, disappears from the circulating red cell with a half-time value of 15.5 days. This accounts for a daily replacement of the total SM pool by 3.2 %.

Factors influencing the degree of erythematous skin reactions in humans

Dose-response relationships have been studied using an ordinal visual scale and reflectance spectrophotometry data from 123 treatment sites on 110 patients treated with 10 dose fractions over 12–14 days. Dose rates varied between 3 and 240 Gy/h and total doses of between 25 and 41 Gy were given using teletherapy apparatus. We found qualitative scoring of erythematous skin reactions to be subject to considerable inter- and intra-observer variation. Reflectance spectrophotometry provided more reproducible information, some of which was undetectable by naked eye. Baseline erythema readings were significantly higher in male patients and at anatomical sites of previous heavy UV exposure. In addition, a pronounced decline in erythema readings during the second week of therapy and ‘reciprocal vicinity’ (abscopal) effects adjacent to the field, undetected by the eye, were observed in a subset of patients. Meaningful dose-response relationships could be derived only from reflectance data with peak change from the pretreatment baseline measure providing the best discrimination. Peak erythema measures following treatment were found to depend on the age and gender of the patient as well as the treatment site and its baseline erythema measurement. This was independent of the total dose administered or the instantaneous dose rate at which it was delivered. The rate of erythema development was also dose rate dependent but only weakly dependent on the biological dose intensity (Gy equiv./day) of the treatment course. The data raise the question of whether irradiation-induced erythema is exclusively a secondary phenomenon occurring as a result of basal cell killing. The short repair half time value of 0.06 h obtained by direct analysis is perplexing and may reflect a dose rate-dependent physiological vasodilatory response to irradiation and/or a multi-component cellular repair process.