The apparent increase in the β-parameter of the linear quadratic model with increased linear energy transfer during fast neutron irradiation

The issue of whether the β-parameter of the linear quadratic model changes with linear energy transfer (LET) remains controversial. Retrospective analysis of UK fast neutron experimental data using human cell lines at Clatterbridge shows that the β-parameter of the linear quadratic model probably does increase with LET during neutron irradiation. For cells without a deficiency in DNA damage repair and for experiments in which β-parameter estimates were considered to be unreliably low, a provisional relationship of β_H = 1.82 β_L was found (where the suffixes refer to high and low LET exposures, respectively). This implies that √β increases by around 1.35 in the specific case of 62.5 MeV neutrons relative to 4 MeV X-rays. Increments in the β-parameter with LET influence the relative biological effect (RBE), especially at high doses per fraction. Large fractions are being used in experimental carbon ion therapy, in which broadly similar RBE values to fast neutrons are found. These interesting findings after fast neutron exposure need to be studied further for applications in charged particle beam therapy using light ions, which is presently undergoing a worldwide expansion.Charged particle radiotherapy offers considerable promise because of the excellent dose distribution achieved owing to the Bragg peak effect [1–4]. However, it is important to take into account the relative biological effect (RBE) when the ionisation events at the microscopic level are especially close, i.e. if the linear energy transfer (LET) is high compared with the megavoltage X-rays.RBE is defined as the ratio of dose of a test radiation to a control radiation, such as cobalt γ-rays or megavoltage X-rays, required to achieve the same bio-effect. RBE varies with dose per fraction in radiotherapy, such that, at very low doses, RBE approaches a maximum value (R_max). This is expressed, in terms of the linear quadratic model of radiation effect, as the ratio of the α-parameters, whereas, at very high doses, it approaches R_min, the ratio of the square roots of the β-parameters (where the suffixes L and H refer to low and high LET radiation, respectively) as follows [5, 6]:(1)At all intermediate doses per fraction, the RBE has an intermediate value between these limits.There is some controversy regarding the theoretical prediction from microdosimetry considerations by Goodhead [7] that both α- and β-parameters increase with LET in order to fit experimental data. It is clear that the largest effect with LET is an increment in α [8]; longstanding in vivo experience has shown an increase in the α/β ratio or reduced fractionation sensitivity with the use of high-LET radiations, such as neutrons [9]. Some experiments have failed to show an increment in β with LET, e.g. Chapman et al [10, 11] showed no increase in √β with LET in plateau-arrested Chinese hamster ovary (CHO) cells. In contrast, experiments in Japan showed a probable increase in the β-parameter [12]. Further evidence from fast neutron studies in vivo has shown that, at the higher dose ranges needed for bio-effects in normal tissues, the value of RBE tends to reach an asymptotic lower (minimum) level, which exceeds unity in the higher dose range [7]. This provides an apparent justification for β increasing with LET. However, historical animal experiments can be criticised because dose cannot be increased further than certain biological limits (associated with death or severe radiation effects), and also because variations in experimental techniques, such as the use of priming doses, could influence the measured RBE.One alternative method for investigating this enigma is to use previously published experimental data of human cell line irradiation using megavoltage X-rays and fast neutrons on the Clatterbridge cyclotron [8]. These data were used to determine α and β values and the RBE, but are amenable to further analysis.     

Efficacy of “touch” DNA recovery and room-temperature storage from assault rifle magazines

Crimes committed with assault rifles are becoming increasingly prevalent in the United States. In the absence of other evidence, DNA analysis can often provide informative leads. Unfortunately, any DNA transferred to rifle components left behind at a crime scene is likely to be low in quantity and/or quality. Furthermore, collected evidence is unlikely to be processed immediately and may require storage. Long-term storage can subject DNA to damage and degradation, which ultimately affects DNA profile interpretation and may prevent the identification of potential suspects.This study assessed the ability of a new swab storage device, the SwabSaver®, to preserve “touch” DNA from AR-15 magazine rifles using three different collection devices. Three volunteers loaded bullet cartridges into plastic polymer and aluminum AR-15 magazines. DNA was collected with traditional cotton swabs, layered cotton paper swabs, or nylon-flocked swabs. Collection devices were then stored at room-temperature for up to two months in either the SwabSaver® device or an empty centrifuge tube. The results suggest that substrate and swab type had less of an effect on profile completeness than storage type. Furthermore, SwabSaver® storage yielded DNA quantities comparable to “touch” DNA extracted after 24 h.     

Prognostic value of left ventricular mechanical dyssynchrony by phase analysis in patients with non-ischemic cardiomyopathy with ejection fraction 35-50% and QRS < 150 ms

Background

Left ventricular mechanical dyssynchrony (LVMD) by phase analysis of gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a useful tool for predicting response to cardiac resynchronization therapy and has prognostic value. While most of the studies were done on patients with ischemic cardiomyopathy or those with LV ejection fraction (EF) < 35%, there are little data on the prognostic value of LVMD in patients with non-ischemic cardiomyopathy (NICM), particularly those with mildly decreased systolic function and narrow or intermediate QRS duration.

Methods and Results

From the stress SPECT-MPI database at Cleveland Clinic, we identified 324 consecutive patients (mean age 62 ± 13 years, 62% male, 36% diabetics) with NICM, LVEF 35-50% (median [Q1,Q3] 45 [41,49]), and QRS < 150 ms (13% with QRS 120-149 ms). LVMD was determined from gated stress images and expressed as phase standard deviation (SD) and histogram BW (% R-R cycle). For easier graphical illustration, patients were divided into tertiles of LVMD. All-cause death was the primary endpoint and determined using the Social Security Death Index. Cox proportional hazard model was performed to determine the independent predictive value of LVMD, and next Cox models for incremental value. After a mean follow-up time of 1,689 days, 86 (26.5%) of patients died. These patients were older, had more diabetes, more use of diuretics, with wider QRS duration, and with a trend for higher phase SD and BW. After adjusting for age, hypertension, diabetes, aspirin, beta-blockers, diuretics, QRS, and EF, phase SD was an independent predictor of all-cause mortality with hazard ratio [95% CI] 1.97 [1.06,3.66] for the highest tertile, and added incremental prognostic value (P = .025). Similar findings were obtained using histogram BW.

Conclusion

In patients with NICM, EF 35-50%, and QRS < 150 ms, increased LVMD on peak stress SPECT was an independent predictor of all-cause mortality. The utility and applicability of such findings in clinical practice need further evaluation in larger and prospective studies.     

Usefulness of <Superscript>123</Superscript>I-metaiodobenzylguanidine myocardial scintigraphy for predicting the effectiveness of β-blockers in patients with dilated cardiomyopathy from the standpoint of long-term prognosis

Purpose The usefulness of ¹²³I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in predicting the effectiveness of -blocker therapy in dilated cardiomyopathy (DCM) was investigated from the standpoint of long-term prognosis.Methods The subjects were 53 DCM patients in whom -blockers had been successfully introduced and used for 6 months or longer. When symptoms were stable before the introduction of -blockers and for up to 1 year thereafter, MIBG myocardial single-photon emission computed tomography was performed and the images analysed to obtain the extent score (EXT), severity score (SEV) and washout rate (WR). At the same time, echocardiography was performed to measure left ventricular ejection fraction (LVEF). Thereafter, patients were placed under observation for an average of 1,314±986 days, with the occurrence of cardiac events as the endpoint.Results The degree of improvement in WR after introduction of -blockers was a significant predictor of cardiac events. In fact, none of the patients whose improvement in WR was valued at 10 or higher had cardiac events. Accordingly, using improvement in WR of 10 as the cut-off value, the patients were divided into two groups, improved and unimproved. There were significant differences between the groups in respect of early EXT, early SEV and WR before the introduction of -blockers . As regards predictors of WR improvement, multivariate logistic regression analysis demonstrated that early EXT, WR and LVEF were significant predictors.Conclusion This study shows that, from the standpoint of long-term prognosis, DCM patients who would benefit the most from -blocker therapy are those with low early EXT and early SEV and high WR before -blocker introduction regardless of LVEF values.     

Clearance of99mTc-diisopropyl-IDA in the “steady state”

A 77-year-old man with a stent in place for biliary drainage was examined. Intravenously administered^99mTc-diisopropyl-IDA showed little accumulation of activity in the abdomen while the stent was draining internally. Upon switching the stent to external drainage, it was possible to monitor the slow movement of the bile which contained radioactivity. Imaging over the liver and comparing activity changes with a^99mTc standard showed that the decrease in hepatic radioactivity was identical to that occurring in the^99mTc standard. The liver was thus in a steady state for excretion of the^99mTc hepatobiliary agent, for it was extracting as much radioactivity from the circulation as it was excreting.Supported by grant no. USPHS CA 17802 from the National Cancer Institute     

Utility of the “buddy” wire in intracranial procedures

Patients undergoing neurointerventional procedures with excessively tortuous vascular anatomy often have limited treatment options. The ability to pass and maintain the stability of micro-guidewires, catheters, and interventional devices is often a product of guide catheter steadiness. A companion wire passed through the lumen of the guide catheter to increase the guide catheter’s stiffness can overcome the challenges associated with tortuous anatomy; this companion wire is referred to as a “buddy” wire. We demonstrate the technical success of this system by presenting a patient whose endovascular treatment would have otherwise been impossible without a “buddy” wire.     

201Tl in the scintigraphic evaluation of the “cold” thyroid areas

²⁰¹Tl-chloride, which has a metabolic behaviour similar to that of potassium and cesium, has been used in 68 patients for the evaluation of thyroid nodules previously recognized as cold on ¹³¹I or ^99mTc scans.All patients were re-examined with gamma-camcra and/or sequential scintigraphic recordings during 60 min after i.v. administration of thallium. In some cases, simultaneous imaging and integral digital plot with ¹³¹I or ^99mTc and ²⁰¹Tl were performed.In all 12 malignant nodules, ²⁰¹Tl has showed a high uptake, while it did not concentrate in 47 benign nodules (cystic or macrofollicular adenomas); thallium uptake was nevertheless found in 10 solid neoformations in which histological pictures were negative for malignancy or atypical lesions.The computerized study of the ²⁰¹Tl intranodular concentration, with the analysis of its dynamic function curves, seems to offer further possibility in differentiating and in a more objective evaluation of the cold areas on the thyroid scan.     

Location of the “zero zone” and its role in the pathogenesis of cervical spondylosis

Summary Significant correlation between the location of the zero zone and spondylosis was found in the cervical spine. The possible role of the zero zone in the development of spondylosis is suggested and the deleterious effect of counteracting forces as compared with a unidirectional traction is stressed.

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Die Stelle der Nullzone und ihre Rolle in der Pathogenese der zervikalen Spondylose

Zusammenfassung Die Ergebnisse der dynamischen Studien scheinen darauf hinzuweisen, daß ein Zusammenhang zwischen den häufigsten Stellen der Nullzone und der Spondylose besteht. Es scheint, daß das Bindegewebssystem der Halswirbelsäule auf die Überlastung durch entgegengesetzte Zugkomponenten sehr empfindlich ist und durch diese stärker beschädigt wird als durch eine Traktion, die nur in einer Richtung ausgeübt wird.

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Localisation de la zone zero et son rôle dans la pathogenie de la spondylose cervicale

Résumé Il semble y avoir une corrélation entre la zone zéro et le développement d'une spondylose cervicale et que la détérioration discale se fasse spécialement au niveau des mouvements intervertébraux bidirectionnels opposés.

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From the annual congress of the European Society of Neuroradiology (Geilo, September 1975)     

“It's all in the history”: A service evaluation of the quality of radiological requests in acute imaging

IntroductionThe aim of this service evaluation project was to assess the quality of clinical details provided in radiological requests.MethodsA retrospective review of adult inpatient and emergency department radiological requests over a seven-day period was performed, using the local Clinical Radiological Information System (CRIS). Requests for plain film, CT, MRI and Ultrasound were assessed for the inclusion of a clinical question, lateralisation/localisation of signs or symptoms if required, and relevant past medical/surgical history if available.Results1548 imaging requests were analysed. 76% asked a specific clinical question. 74% of requests requiring localisation provided this. Of those cases with relevant past medical or surgical history available, 49% mentioned this. Emergency department (ED) requests provided localisation when required in 81% of cases compared to 62% of in-patients (p < 0.05). However, in-patient requests contained relevant past history in 53% of cases compared to 40% for ED requests (p = 0.00096). Compared to plain film requests, those for CT, MRI and Ultrasound studies were more complete in respect to inclusion of a clinical question (88% versus 72%, p < 0.05), localisation if required (83% versus 71%, p = 0.0007) and pertinent clinical history (67% versus 42%, p < 0.05). Requests from the weekend more often included a clinical question (83% vs 75%, p = 0.00054) and localisation if needed (84% vs 71%, p = 0.00188) compared with weekday requests.ConclusionThis large-scale service evaluation project shows that the quality of clinical details in requests for radiological investigations requires improvement, particularly in regard to inclusion of relevant past medical and surgical history.     

Analysis of the prevalence and coexistence of synthetic cannabinoids in “herbal high” products in Poland

“Herbal highs” are a group of products marketed in recent years as legal substitutes for marijuana. This article presents the results of examinations performed on samples seized in “head shops” and from individuals during a 3.5-year period, between mid-2008 and the end of 2011 in Poland. Of over 2000 samples delivered for analysis, 420 preparations were selected for this study. Gas chromatography–mass spectrometry and liquid chromatography–quadrupole-time-of-flight–mass spectrometry were used for identification of psychoactive components, and high-performance liquid chromatography was used for their quantitation. The most common ingredients of herbal highs were: JWH-081 (144 products), JWH-018 (103), RCS-4 (92), JWH-073 (89), JWH-250 (75), JWH-122 (69), cannabicyclohexanol (55), and JWH-210 (38). Over 50 % of the products contained two or more active ingredients; 136 products (32.4 %) contained two; 56 products (13.3 %) contained three; and 22 (5.2 %) contained more than three. Common combinations of ingredients were investigated by the graph method; substances coexisted mainly with those introduced into the drug market in a similar period of time. The most common dual combinations were JWH-081 + RCS-4 (18 products), JWH-073 + JWH-250 (16), and JWH-081 + JWH-250 (12). JWH-081 was blended with almost all detected synthetic cannabinoids. The main risks of the use of these substances were due to ignorance of great variation in the content and composition of synthetic cannabinoids even if the products had identical labels. This inconsistency could cause serious health damage to users, while ignorance of the fact that more than one third of the products being sold at head shops contain illicit compound(s) could result in unexpected arrest.     

Ossification and pseudoepiphysis formation in the “nonepiphyseal” end of bones of the hands and feet

Metacarpals, metatarsals, and phalanges were studied to assess the developmental morphology of secondary ossification in the nonepiphyseal ends of these bones as well as the formation of the pseudoepiphysis as an epiphyseal ossification variant. Both direct ossification extension from the metaphysis into the epiphysis and pseudoepiphysis formation preceded, and continued to be more mature than, formation and expansion of the classic epiphyseal (secondary) ossification center at the opposite end of each specific bone. Direct metaphyseal to epiphyseal ossification usually started centrally and expanded hemispherically, replacing both physeal and epiphyseal cartilage simultaneously. In contrast, when remnants of physis were retained, while juxtaposed epiphyseal cartilage was replaced, a pseudoepiphysis formed. There were three basic patterns of pseudoepiphysis formation. First, a central osseous bridge extended from the metaphysis across the physis into the epiphysis and subsequently expanded to create a mushroom-like osseous structure. In the second pattern a peripheral osseous bridge formed, creating either an osseous ring or an eccentric bridge between the metaphysis and the epiphysis. In the third pattern, multiple bridging occurred. In each situation the associated remnant physis lacked typical cell columns and was incapable of significantly contributing to the postnatal longitudinal growth of the involved bone. Pseudoepiphyses were well formed by 4–5 years and coalesced with the rest of the bone months of years before skeletal maturation was attained at the opposite epiphyseal end, which ossified in the typical pattern (i.e., formation of a secondary center de novo completely within the cartilaginous epiphysis). This process may also affect the development and appearance of ossification within the longitudinal epiphyseal bracket (delta phalanx).     

Quantitative angioscopy: A novel method of measurement of luminal dimensions during angioscopy with the use of a “lightwire”

Purpose To determine the accuracy and reproducibility of luminal dimension measurements of a newly developed method of quantitative angioscopy.Methods A method was developed for quantitation of luminal dimensions during angioscopy, as variation in magnification with lens-object distance and ambiguity associated with identification of corresponding points about the circumference of a given discrete cross-section render subjective estimates unreliable. A transverse ring of fiberoptically transmitted light was emitted from a guidewire or its housing at a known distance from the distal end of an angioscope and discrete cross-sections of interest were observed as the ring of light was reflected from the luminal surface. Caliper measurement of the diameter of the light ring image (< 50 mW at 488/515 nm), obtained on angioscopic video recordings of cylindrical phantom vessels of known dimensions, was performed by three observers on five occasions.Results The mean absolute difference between measured and known luminal diameter (n = 405 observations) was 65 m±35 m and the mean coefficient of variation was 4.2%, and the mean difference between measured and known areas (n = 195 observations) was 0.4 mm², with a mean coefficient of variation of 6.5%.Conclusion By use of this new lightwire method, luminal dimensions can now be measuredin vitro with a high degree of accuracy and reproducibility during angioscopy.Presented in part at the 41st Annual Scientific Session of the American College of Cardiology, Anaheim, California, March 1993.     

The “mini brain” appearance of plasmacytoma in the appendicular skeleton

We report on the case of a 70-year-old woman presenting with right hip pain. Radiographs of the right hip demonstrated a well-defined large lytic lesion in the proximal right femur, with prominent trabeculae situated peripherally and extending into the lesion in a "spoke-wheel" pattern. Magnetic resonance imaging (MRI) demonstrated solid enhancing marrow-replacing lesion, with intervening linear nonenhancing areas of low T2 signal intensity. The MRI appearance resembled that of a small brain or "mini brain". Biopsy specimen demonstrated predominantly mature plasma cells, with occasional admixed immature forms. A diagnosis of plasmacytosis, consistent with myeloma, was made. This case illustrates a rare but seemingly characteristic "mini brain" appearance of plasmacytoma, which, to date, has only been reported in the spine and has not been observed in other bony lesions.     

Optimization and Standardization of the “Comet Assay” for Analyzing the Repair of DNA Damage in Cells

BACKGROUND: The "comet assay" has become an interesting and a very useful tool for the analysis of the induction and amount of DNA damage in single cells thus offering the opportunity to measure the effectiveness of DNA repair. On the basis of the Ostling and Johanson protocol we have developed a modified method with increased sensitivity and high reproducibility. MATERIAL AND METHODS: Human tumor cells or isolated human peripheral blood lymphocytes were analyzed in the experiments. The amount of DNA damage and the effectiveness of DNA repair was measured after X-irradiation using the "comet assay" technique. RESULTS: In this presentation the influences of different methodological factors like agarose concentration, buffer pH, electrophoresis time, electric field strength on the applicability of the "comet assay" are described in detail and optimum conditions for "comet assay" experiments have been evaluated. Additionally the authors will show a comparison of different fluorescent DNA dyes pointing out their advantages or disadvantages for "comet" analysis. The usefulness of this technique and its capabilities are exemplified by showing DNA repair kinetics of human lymphocytes of different healthy or radiosensitive donors after in-vitro irradiation with 2 Gy X-rays. CONCLUSIONS: This paper presents data on the optimization and standardization of the original "comet assay" leading to an extremely fast and practicable protocol in the field of single cell gel electrophoresis. After irradiation with 0.1 Gy an increase in the amount of DNA damage can be measured with high statistical significance and the DNA repair capacity of individual cells after X-ray doses of 2 Gy can be analyzed with high reproducibility. The results comparing DNA repair capacities of different donors point out that the "comet assay" may have the potential for the estimation of individual radiosensitivity.     

201Tl gated single photon emission computed tomographic myocardial perfusion imaging in the assessment of global and regional left ventricular function. Would it be favoured over equilibrium radionuclide angiography?

BACKGROUND: This study investigates the clinical performance of routine 201Tl gated single photon emission computed tomographic (201Tl GSPECT) myocardial perfusion imaging. Equilibrium radionuclide angiography (ERNA) was used as the standard for comparison. METHODS AND RESULTS: One hundred and seventy-two consecutive patients were submitted to both myocardial 201Tl GSPECT imaging, at stress and in redistribution, and ERNA. Left ventricular ejection fractions (LVEF) and regional wall motion were assessed from both stress and redistribution 201Tl GSPECT datasets, and from ERNA. Linear regression analysis showed a good correlation between LVEF calculated by ERNA and 201Tl GSPECT (r=0.73 at stress, r=0.75 in redistribution, P<0.0001). However, the 95% prediction intervals of 201Tl GSPECT LVEF from ERNA LVEF were wide (minimum 35.4% at stress and 33.2% in redistribution). Moreover, a difference in LVEF > or =10% between ERNA and 201Tl GSPECT was found in 26.4% of cases at stress and 28.6% of cases in redistribution. A fair agreement between ERNA and 201Tl GSPECT was found in regional wall motion assessment in segments with normal or mildly reduced tracer uptake (kappa=0.32 at stress and kappa=0.33 in redistribution). In segments with moderately to severely reduced tracer uptake, a moderate agreement was found in regional wall motion assessment between ERNA and 201Tl GSPECT (kappa=0.44 at stress and kappa=0.42 in redistribution). CONCLUSIONS: Left ventricular function may be misinterpreted in a significant proportion of patients if the calculation of LVEF is based on 201Tl GSPECT. Moreover, the evaluation of regional wall motion by 201Tl GSPECT appears unsatisfactory.     

Usefulness of the “Rendezvous” Technique in Living Related Right Liver Donors with Postoperative Biliary Leakage from Bile Duct Anastomosis

This is a report on two cases of large bile leak following right hepatectomy performed for living related liver transplantation, originating from the stump of the ligated right bile duct, and treated with the placement of large percutaneous biliary catheters through a combined percutaneous transhepatic and endoscopic approach (rendezvous technique).