Anti-inflammatory activity of the sesquiterpene lactone diacethylpiptocarphol in dextransulfate sodium-induced colitis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Sesquiterpene lactones are organic compounds derived mainly from plants that exhibit anti-inflammatory and antitumor activities being one of the key mechanism of action of NF-kB pathway and synthesis of cytokines such as IL-1 and TNF- α. AIM OF THE STUDY: The overall objective of the present study was to evaluate the anti-inflammatory action of a sesquiterpene lactone diacethylpiptocarphol (DPC) from Vernonia scorpioides (Lam.) Pers. and parthenolide (PTH) in Balb-c mice with DSS-induced colitis. MATERIALS AND METHODS: The anti-inflammatory effects of Intraperitonial administration of DPC (5 mg/kg/day) were evaluated in Balb/c mice with DSS-induced colitis, and further the body weight measurement, TNF-α and TGF-ß level was determined. RESULTS: After intraperitoneal treatment for one week, DSS-induced colitis was significantly reduced in mice treated with either of both sesquiterpenes lactones, as witnessed by reduced cellular infiltration, tissue damage, TNF-α production, and enhanced production of TGF-ß. CONCLUSIONS: Sesquiterpene lactone DPC, isolated from Vernonia scorpioides showed anti-inflammatory activity, in this experimental model of colitis the sesquiterpene lactones DPC and PTH exhibit equal anti-inflammatory activity.

Influence of mycotoxin binders on the oral bioavailability of tylosin, doxycycline, diclazuril, and salinomycin in fed broiler chickens.

The presence of mycotoxins in broiler feed can have deleterious effects on the wellbeing of the animals and their performance. Mycotoxin binders are feed additives that aim to adsorb mycotoxins in the intestinal tract and thereby prevent the oral absorption of the mycotoxin. The simultaneous administration of coccidiostats and/or antimicrobials with mycotoxin binders might lead to a reduced oral bioavailability of these veterinary medicinal products. This paper describes the influence of 3 mycotoxin binders (i.e., clay 1 containing montmorillonite, mica, and feldspars; clay 2 containing montmorillonite and quartz; and yeast 1 being a modified glucomannan fraction of inactivated yeast cells) and activated carbon on the oral bioavailability and pharmacokinetic parameters of the antimicrobials doxycycline and tylosin, and the coccidiostats diclazuril and salinomycin. A feeding study with 40 15 day-old broilers was performed evaluating the effects of long-term feeding 2 g mycotoxin binder/kg of feed. The birds were randomly divided into 5 groups of 8 birds each, i.e., a control group receiving no binder and 4 test groups receiving either clay 1, clay 2, yeast 1, or activated carbon mixed in the feed. After 15 d of feeding, both the control and each test group were administered doxycycline, tylosin, diclazuril, and salinomycin, consecutively, respecting a wash-out period of 2 to 3 d between each administration. The 4 medicinal products were dosed using a single bolus administration directly in the crop. After each bolus administration, blood was collected for plasma analysis and calculation of the main pharmacokinetic parameters and relative oral bioavailability (F = area under the plasma concentration-time curve (AUC0-8 h) in the test groups/AUC0-8 h in the control group)*100). No effects were observed of any of the mycotoxin binders on the relative oral bioavailability of the coccidiostats (i.e., F between 82 and 101% and 79 and 93% for diclazuril and salinomycin, respectively). Also, no significant effects could be noticed of any of the mycotoxin binders on the relative oral bioavailability of the antimicrobials doxycycline and tylosin (i.e., F between 67 and 83% and between 43 and 104%, respectively).

Genetic damage in humans exposed to extremely low-frequency electromagnetic fields.

The classification of extremely low-frequency magnetic fields by the International Agency for Research on Cancer in the group of 'possible human carcinogens' (group 2B) is essentially based on epidemiologic evidence showing an association between MF exposures and childhood leukaemia. Despite many in vitro and in vivo investigations, there is no established causal relationship yet. However, human cytogenetic biomonitoring studies that were conducted in the past show predominantly positive results, i.e. increased cytogenetic damage in peripheral blood lymphocytes or buccal cells of ELF-MF-exposed subjects. This is important given the established link between observed cytogenetic damage in cells of people and an increased cancer risk. We here conducted an evaluation of the published investigations and found that many of the studies clearly have shortcomings, which often prevent any firm conclusion. As a matter of fact, there are reasons to believe that effects are not that impressive. However, the totality of the studies cannot simply be disregarded warranting further caution and the application, to a certain extent, of the precautionary principle.

How peer conversations about HIV/AIDS media messages affect comprehension and beliefs of young South African women.

Most existent research on the effects of interpersonal discussions about health campaign messages is based on surveys. In this study, we analysed actual conversations about an HIV/AIDS poster to find out possible effects. Young South African women in 59 dyads (n = 118) participated in conversations about a deliberately puzzling HIV and AIDS poster that cautioned the target group to be faithful to one sexual partner. We measured their comprehension of the poster and beliefs about the message, before and after the conversations. Overall, actual comprehension (AC) was low, and we observed a large discrepancy between actual and perceived comprehension. In general, conversations did not improve AC. It proved to be even more probable that a correct interpretation before a conversation turned into an incorrect interpretation than the other way around. However, having a well-informed conversation partner increased the chance of acquiring adequate subsequent comprehension. We found, in general, that conversations did not decrease undesirable beliefs. One important undesirable belief even became reinforced after the conversations. Conversations among peers might be valuable in health campaigns, but our study shows that intended positive effects do not automatically follow.

Topical distribution of acyclovir in normal equine skin and equine sarcoids: An in vitro study.

Topical acyclovir application is an owner-friendly treatment for occult equine sarcoids, without the caustic side-effects other topical treatments have. Variable clinical success rates have been described, but it is not known to what rate and extent acyclovir penetrates in and through equine skin from a topical formulation. In the current study, an in vitro Franz diffusion model was used to determine the permeation parameters for a generic 5% acyclovir cetomacrogol cream for both healthy and sarcoid equine skin. The distribution of acyclovir between different layers of both skin types was also evaluated. While acyclovir penetrated through both skin types, significantly less acyclovir permeated to the deep dermis of sarcoid skin (197.62ng/mm(3)) compared to normal skin (459.41ng/mm(3)). Within sarcoid skin samples, significantly higher acyclovir concentrations were found in the epidermis (983.59ng/mm(3)) compared to the superficial dermis (450.02ng/mm(3)) and the deep dermis. At each sample point, significantly more acyclovir permeated to the receptor fluid through normal skin compared to sarcoid skin, which is reflected in the significantly higher permeation parameters of normal skin. Normal skin was found to be more permissive for acyclovir, but even in sarcoid skin, enough acyclovir reached the deep dermis to treat a Herpes simplex virus infection. In the case of equine sarcoids, the treatment is aimed at the Bovine papillomavirus and no information is available on the susceptibility of the DNA polymerase of this virus for acyclovir. Therefore, further research is needed to determine the efficacy of acyclovir to treat equine sarcoids.

An accessory skull suture mimicking a skull fracture.

This paper describes an investigation of the sudden and unexpected death of a five-and-a-half-month-old boy. As in every Dutch case of sudden unexpected death in infancy (SUDI), a multidisciplinary diagnostic approach was used. This included post-mortem radiography, showing a linear discontinuity of the parietal bone. Originally this was interpreted as a skull fracture, but autopsy indicated no signs of mechanical trauma. Instead the defect was defined as a unilateral accessory suture of the parietal bone. The initial erroneous diagnosis had severe adverse consequences and thus every health care professional or forensic specialist dealing with paediatric mechanical traumas should be cautious of this rare anomaly.

Protein S-nitrosylation in photosynthetic organisms: A comprehensive overview with future perspectives.

BACKGROUND: The free radical nitric oxide (NO) and derivative reactive nitrogen species (RNS) play essential roles in cellular redox regulation mainly through protein S-nitrosylation, a redox post-translational modification in which specific cysteines are converted to nitrosothiols. SCOPE OF VIEW: This review aims to discuss the current state of knowledge, as well as future perspectives, regarding protein S-nitrosylation in photosynthetic organisms. MAJOR CONCLUSIONS: NO, synthesized by plants from different sources (nitrite, arginine), provides directly or indirectly the nitroso moiety of nitrosothiols. Biosynthesis, reactivity and scavenging systems of NO/RNS, determine the NO-based signaling including the rate of protein nitrosylation. Denitrosylation reactions compete with nitrosylation in setting the levels of nitrosylated proteins in vivo. GENERAL SIGNIFICANCE: Based on a combination of proteomic, biochemical and genetic approaches, protein nitrosylation is emerging as a pervasive player in cell signaling networks. Specificity of protein nitrosylation and integration among different post-translational modifications are among the major challenges for future experimental studies in the redox biology field. This article is part of a Special Issue entitled: Plant Proteomics--a bridge between fundamental processes and crop production, edited by Dr. Hans-Peter Mock.

Secondary non-Hodgkin lymphoma of the ethmoid sinus after temozolomide.

The paranasal sinuses are rarely the site of malignancy, especially non-Hodgkin lymphoma. In such cases, the ethmoid sinus is the second most frequently involved paranasal sinus. Diagnosis of these malignancies is difficult because the early symptoms often mimic benign sinus pathology. Thus, most cases are diagnosed at an advanced stage, and their prognosis is poor. Here we describe the case of a 58-year-old man with a secondary high-grade B-cell non-Hodgkin lymphoma of the ethmoid sinus. This malignancy was diagnosed two years after the patient had received treatment with temozolomide for a glioblastoma multiforme. This case highlights that malignant tumours of the paranasal sinuses should always be included in the differential diagnosis of sinus disease. Additionally, patients treated with temozolomide should receive regular follow-up care including vigilant evaluation for secondary tumours, such as non-Hodgkin lymphoma.

Reproducibility of FDG PET based metabolic tumor volume measurements and of their FDG distribution within.

AIM: The aim of this study was to report on the reproducibility of F-18-fluorodeoxyglucose (FDG) PET MTV (metabolic tumor volume) 40% and MTV2.5, as well as on the intratumor reproducibility in patients, predominantly suffering from lung cancer and squamous cell carcinoma of the head and neck (SCCHN). METHODS: Nineteen patients (14 men) who underwent a baseline staging FDG PET-CT examination and a second radiotherapy treatment planning FDG PET-CT examination prior to treatment initiation within 17 days (range: 7-37 days) from each other were included. Bland-Altman analysis was performed on MTV40% and MTVSUV2.5 values obtained of the primary tumor. For voxelwise comparison of the FDG distribution within tumors the transformation matrices, defined on the CT images, were applied to the corresponding FDG images. Accordingly, the MTV40% of the primary tumor volume was defined and copied on the second FDG image. The coordinates and SUV values of each pixel in the corresponding volumes in both FDG images were used for paired comparison. RESULTS: The standard deviation of the percentage spread around the means of both measurements was respectively 32.5% for MTVSUV2.5 versus 18.8% for MTV40%. Using a cut-off value of 1.96 SD, differences exceeding 64% in MTVSUV2.5 and 37% in MTV40% may be considered to be clinically relevant. Correlation coefficients derived from the voxelwise paired comparison of SUV values within MTV40% volumes delineated on scan 1 and scan 2 ranged from 0.67 to 0.96 (mean: 0.83). Bland-Altman plots demonstrated a low reproducibility for low SUV values and a high(er) reproducibility for high SUV values (inverted triangular shape) in all tumor volumes under study. CONCLUSION: The reproducibility of MTV40% proved better than that of MTVSUV2.5 with a cut-off of 37% (increase or decrease) in MTV allowing to define clinically significant changes. Furthermore, intratumoral voxelwise FDG distribution did not change significantly in most of the patients during the time interval studied.

CA 15.3 measurements for separating FDG PET/CT positive from negative findings in breast carcinoma recurrence. Factors influencing the area under the ROC curve.

UNLABELLED: In breast cancer CA 15.3 is considered the tumour marker of choice. CA 15.3 is directly related to the disease extent and to hormone status (estrogen receptor ER+/ ER-, progesterone receptor PR+/PR-). This study was designed to assess the impact of disease extent, hormone receptor and HER2-status, and circulating blood volume on the area-under the ROC-curve of CA 15.3 to separate FDG PET positive from negative findings. PATIENTS, METHODS: We retrospectively evaluated 379 FDG PET/CT examinations performed in 80 patients with breast cancer. Blood volumes were derived using the formulas by Nadler and multiplied by their corresponding CA 15.3 measurement. RESULTS: ROC-curve analysis revealed an AUC of 0.695 (p = 0.0001) for CA 15.3 to separate FDG PET positive from negative findings. AUC measurements to separate normal scan findings from loco-regional disease and metastatic disease were 0.527 (p = 0.587) and 0.732 (p = 0.0001), respectively. AUC measurements for CA 15.3 to separate positive from negative FDG PET findings, in ER+ and ER- patients, were respectively 0.772 (p = 0.0001) and 0.596 (p = 0.143). AUC measurements for CA 15.3 to separate positive from negative FDG PET findings, in PR+ and PR- patients, were respectively 0.675 (p = 0.0001) and 0.694 (p = 0.0001). In HER2-positive and -negative patients, the AUC measurements were respectively 0.594 (p = 0.178) and 0.701 (p = 0.0001) to separate positive from negative FDG PET findings. CONCLUSION: The AUC for CA 15.3 measurements to separate FDG PET positive from negative findings in breast cancer patients with suspected recurrence proved to be directly related to the extent of the recurrent disease and hormone receptor status and inversely related to HER2-status. Correcting CA 15.3 measurements for blood volumes did not impact the AUC.

Targeting monocytes and macrophages by means of SPECT and PET.

Monocytes have been isolated from patient's blood and directly radiolabelled in vitro using a variety of radiopharmaceuticals such as 99mTc-HMPAO, 111In-oxine, 99mTc-colloids and 18F-FDG. Overall, the best labeling results were obtained using 99mTc-HMPAO. The wide availability of 99mTc and of the ligand HMPAO in kit-formulation makes it the most versatile procedure for imaging localized inflammation using in-vitro labeling. Injection of 99mTc-HMPAO labeled monocytes in adult patients has proven safe with an effective dose of 0.011 mSv/Mbq, equivalent to that of 99mTc-HMPAO labeled mixed white blood cells. Furthermore, in a proof of concept studies, in-vitro labeled monocytes were shown to specifically accumulate in the bowels of patients suffering from inflammatory bowel disease as well as in inflamed joints of rheumatoid arthritis patients. Inversely, the decrease in disease activity of inflamed joints of rheumatoid arthritis patients treated by Adalimumab could not be substantiated using 99mTc-HMPAO labelled monocytes suggesting this type of treatment does not reduce monocyte influx. In spite of their wide availability, in-vitro labeling procedures are cumbersome and time-consuming. Furthermore, cell activation may occur during the labeling process and it cannot be excluded that the radiopharmaceuticals used for labelling interfere with ongoing cellular processes. As such, various authors turned towards the development of radiopharmaceuticals for in-vivo labeling of both monocytes and more importantly macrophages, many of which were subsequently validated in animal models. Targets studied in this regard include amongst others the folate receptor, the mannose receptor, the peripheral benzodiazepine receptor as well as more general characteristics of macrophages such as phagocytosis. Various of these novel molecules appear promising and clinical studies using these radiopharmaceuticals are awaited in the near future. Some of these radiopharmaceuticals also reached the clinical stage, respectively the translocating protein targeting radiopharmaceutical 11C-PK11195 and the folate receptor targeting radiopharmaceutical 99mTc-EC20. Uptake of 11C-PK11195 in inflamed joints and sites of atherosclerosis in patients proved to be directly related to the number of peripheral benzodiazepine binding receptors available as well as to the severity of ongoing inflammation. Comparable results were obtained using 99mTc-EC20 in rheumatoid arthritis patients. In spite of these promising results, additional studies are warranted demonstrating that in vivo, quantitative visualization of monocyte trafficking and accumulation of M1 or M2 macrophage subtypes in sites of ongoing inflammation by means of SPECT and PET will contribute to a better understanding of human inflammatory diseases as well as to diagnosis, treatment planning and the development of targeted treatment strategies.

The value of post-mortem CT in neonaticide in case of severe decomposition: description of 12 cases.

INTRODUCTION: In cases of neonaticide with delayed finding of the body, interpretation of autopsy results can be difficult because of decomposition. Postmortem computed tomography (PMCT) has become an increasingly popular tool in the (pediatric) forensic field. We performed a retrospective study to compare the outcome of PMCT with autopsy results in suspected neonaticide, in neonates found more than one week after their demise. We compared the performance of both methods on (1) determining gestational age, (2) differentiating between live birth and still birth and (3) determining cause of death. METHOD: We selected all consecutive neonaticide cases with an estimated postmortem interval longer than one week, who underwent a forensic autopsy including a total body PMCT in the Netherlands Forensic Institute in the period 2008-2012. Both a pathologist and radiologist scored gestational age, signs of live birth and cause of death for each case. RESULTS: 22 cases of neonaticide were identified in the study period, of which 15 cases were estimated to be found more than 1 week after death. In 12 of these a total body PMCT was performed. In all cases, late postmortem changes were present. Gestational age could be assessed with PMCT in 100% of the cases and with autopsy in 58% of the cases. In all cases neither PMCT nor autopsy was able to assess live birth and cause of death. CONCLUSION: PMCT is a better tool for estimating gestational age in case of suspected neonaticide with late postmortem changes compared to autopsy and should therefore be a standard part of the work-up. Signs of live birth and cause of death could not be determined with neither of the methods, an adjusted post mortem examination including limited autopsy for these cases might be developed.

Quantitative p retreatment VOI analysis of liver metastases. (99m)Tc-MAA SPECT/CT and FDG PET/CT in relation with treatment response to SIRT.

UNLABELLED: Using quantitive VOI analysis, the percentage (99m)Tc-MAA uptake and SUVmax and mean values of liver metastases obtained prior to SIRT were related to treatment response using both a lesion-based and clinical dichotomous approach. Based on the VOI % of (99m)Tc-MAA activity, the estimated (90)Y-microspheres activity/cc (MBq/cc) was calculated from the effective dose injected. Baseline VOI FDG PET SUVmean and max values and estimated MBq/cc values were related to treatment response using a lesion-based approach (% change in SUVmean ≥ 50%) and a clinical dichotomous approach. Fifteen treatment sessions were analyzed (13 patients). Using the lesion-based approach (12 treatment sessions) 40 lesions responded and 37 did not. SUVmax and mean values proved significantly different between non-responding and responding lesions; 18.6 (SD 10.8) versus 13.5 (SD 8.4 ) for SUVmax (p = 0.02) and 11.4 (SD 3.8) versus 6.3 (SD 4.5) for SUVmean (p = 0.002). Using the clinical dichotomous approach (15 treatment sessions / 11 responding), 91 lesions were analyzed; 57 responded. VOI volumes and estimated (90)Y-loaded glass microspheres activity (MBq/cc) did not differ between responders and non responders; 24 cc (SD 27) versus 21 cc (SD 21 cc) (p = 0.4) and 1.95 MBq/cc (SD 1.1 MBq/cc) versus 1.90 MB/cc (SD 2.7 MBq/cc) (p = 0.92). On the contrary, SUVmax and mean values proved significantly different between responders and non-responders; 23.7 (SD 9.8) versus 9.4 (SD 3.8 ) for SUVmax (p = 0.0001) and 13.1 (SD 8.1) versus 4.9 (SD 1.4) for SUVmean. CONCLUSION: These findings suggest that in patients presenting with high baseline SUVmax and mean values, the administration of higher activities or alternatively, other potentially more useful treatment options might be considered.

Testing chemical agents with the cytokinesis-block micronucleus cytome assay.

In order to evaluate the applicability of the cytokinesis-block micronucleus cytome assay in routine mutagenicity testing we investigated with this method different chemicals having different mechanisms of action: non-mutagens, direct-acting basealtering mutagens, direct-acting cross-linking mutagens, clastogens including a radiomimetic chemical, indirect-acting spindle poisons and indirect-acting enzyme inhibitors. We looked at the presence of micronuclei as biomarkers for either the loss of chromosome fragments (clastogen) or the loss of a whole chromosome (aneugen), nucleoplasmic bridges as biomarkers for complex rearrangements (e.g., dicentric chromosomes) and nuclear buds as biomarkers for gene amplification. The cytome assay proved to be a suitable tool to investigate genetic effects of environmental agents and to provide insight into their working mechanisms as all chemicals tested showed the expected response.

FDG uptake in lymph-nodes of HIV+ and tuberculosis patients: implications for cancer staging.

AIM: The incidence of non-AIDS-related cancers (NADCs) in the AIDS-population has surpassed that of the general population. HIV significantly increases an individual's chances of reactivation of latent tuberculosis (TB) infection and progression to active TB disease. Both HIV, TB and CA present with increased FDG uptake in involved lymph nodes (LNs). The aim of this study was to assess the existence of quantitative differences in FDG uptake by lymph nodes in HIV+/TB-/CA- patients, TB+/HIV-/CA-, TB+/HIV+/CA- patients and HIV-/TB-/CA+ patients. METHODS: Sixteen consecutive referred patients suffering from HIV-1, 21 suffering from HIV-1 and TB and 16 suffering from TB alone were prospectively included. In addition, 30 consecutively referred, previously untreated, HIV and TB negative cancer patients were included. All patients underwent FDG PET imaging. Mean standardized uptake values (SUV mean values) were obtained for involved lymph nodes using region growing and a threshold of 30% in all patients. Results obtained were compared using non-parametric statistics. RESULTS: SUVmean values of involved LNs of HIV+/TB+/CA- patients were significantly higher than SUVmean values of involved LNs of HIV-/TB+/CA- patients and HIV+/TB-/CA patients (P<0.05). Also, SUVmean values of involved LNs of HIV-/TB-/CA+ patients were significantly higher than SUVmean values of involved LNs of HIV+/TB-/CA- patients. HIV+/TB+/CA- patients presented with a significantly higher number of sites of LN involvement when compared to the HIV+/TB-/CA- patient group. CONCLUSION: FDG PET is not useful for assessing malignant lymph node involvement in HIV+, TB+ or HIV+/TB+ patients.

Collaborative study for the standardisation of the histamine sensitizing test in mice and the CHO cell-based assay for the residual toxicity testing of acellular pertussis vaccines.

The European Pharmacopoeia (Ph. Eur.) and the World Health Organisation (WHO) require the performance of extensive quality and safety control testing before the release on the market of vaccine products for human use. Safety testing with regard to residual pertussis toxin (PT) in acellular pertussis combination vaccines is performed through assessment of fatal sensitisation of mice to histamine challenge by the vaccine product under test. Currently, use of different in-house procedures and no requirement for the inclusion of a standard reference in each assay render comparisons of results obtained for identical vaccine batches between different control laboratories very difficult. At the initiative of the European Directorate for the Quality of Medicines and HealthCare (EDQM), an international collaborative study was organised for the standardization of the Histamine Sensitizing Test (HIST) in mice and the Chinese Hamster Ovary (CHO)-cell-based assay (performed at the bulk product level) for the residual toxicity testing of acellular pertussis vaccines or acellular pertussis-based combination vaccines. The study was run under the aegis of the Biological Standardisation Programme, jointly supported by the Council of Europe and the European Commission under the project code BSP076. Ten (10) laboratories participated in the study and were requested to perform 3 independent Histamine Sensitizing Tests in mice and to report results of the lethal end-point measurement as prescribed by the Ph. Eur. monographs. Some of them also reported data from an in-house validated CHO-cell-based assay. In addition, some of the laboratories reported concomitantly data obtained by measurement of the drop in temperature induced after the histamine challenge, a method currently under investigation to be added as an alternative end-point for the HIST in the Ph. Eur. monographs for acellular pertussis-based combination vaccines in order to alleviate animal suffering (in application of the 3Rs principle). Based on the results of the collaborative study, a potency of 7500 IU/vial (International Units per vial) was assigned to the current Ph. Eur. Biological Reference Preparation (BRP) for PT. The results of the study also show that 1) intra- and inter-laboratory variations can be improved by the use of a validated standard operating procedure; 2) inclusion in each assay of a standard reference sample, calibrated in IU, can increase comparability of results among laboratories and thus help to reduce repeat testing; 3) a correlation between mortality data and temperature data was observed although, due to the limited number of data sets and the lack of a common method for the temperature end-point, further investigation of this point is required; 4) the CHO-cell-based assay did not yield comparable results and further standardisation of the assay procedure may be investigated in a follow-up project.

Impact of FDG PET on the management of TBC treatment. A pilot study.

UNLABELLED: The aim of this study is to assess the potential impact of double-phase FDG PET versus routine staging in HIV-negative patients suffering from tuberculosis. PATIENTS, METHODS: 16 consecutive patients suffering from tuberculosis underwent contrast-enhanced CT and double-phase FDG PET imaging (45 min, 120 min). Early (E) and delayed (D) SUVmax values were determined for all identified lesions and % change in SUV calculated (DeltaSUV). RESULTS: Seven patients presented with lung lesions on PET as well as CT (mean SUVmaxE 8.2, mean SUVmaxD 11.1, (p = 0.002), DeltaSUV 35%. In two patients, lesions were judged as non-active on CT. In nine patients, 18 sites of LN involvement were identified on both early and delayed FDG PET images (mean SUVmaxE 6.3, mean SUVmaxD 7.9, (p = 0.0001), DeltaSUV: 25%). 9 out of 18 sites of LN involvement, occurring in five patients, were missed on CT. In four of these five patients, sites of LN involvement were the only sites of extra-pulmonary involvement identified. In 6 out of 16 patients, pleural involvement was identified, respectively in 5 on FDG PET and in 6 on CT imaging (mean SUVmaxE 1.3, mean SUVmaxD 1.7, (p = 0.06), DeltaSUV 21%). In 4 patients, osseous involvement was identified by both FDG PET and CT (mean SUVmaxE 7.2, mean SUVmaxD 10.7, (p = 0,06), DeltaSUV 45%). Finally, in 3 patients, joint involvement was identified on both FDG PET as well as on CT imaging (mean SUVmaxE 4.7, mean SUVmaxD 5.2, DeltaSUV 23%). FDG PET did not identify CT-additional sites of involvement that would have resulted in a prolonged treatment. CONCLUSION: In HIV-negative patients suffering from tuberculosis, FDG PET images suggested a more extensive involvement by Mycobacterium tuberculosis when compared to contrast enhanced CT.

Support for the hypothesis that electro-stimulation is responsible for Lipoatrophia semicircularis.

Lipoatrophia semicircularis (L.s.) is a idiopathic condition characterised by semicircular impressions of the skin, usually at the front and sides of both thighs. It was first described some 35years ago but only as a case study where a few subjects with L.s. were described. Later on some more cases were diagnosed and described but their number remained low. It is only over the past ten years that an outburst of L.s. was observed. This was first seen in Belgium, later on also in other countries (e.g., Spain) where several hundreds of individuals were diagnosed with L.s. All these subjects belonged to the administrative personnel of diverse companies indicating that this condition is essentially office and job related. Afflicted subjects were mainly women working with computers or with other electrical devices placed on their desk. Furthermore, L.s. was invariably diagnosed after moving into new or renovated office buildings. Hypotheses have been put forward to explain the appearance of L. semicircularis. These hypotheses involve mechanical pressure, blood circulation problems, disturbance of thermal energy exchange and electrostatic discharges or other electric phenomena. In this paper, these hypotheses are considered and new data presented in favour of an "electric" origin of L.s. Earlier published observations on the influence of electric fields from 50Hz, 230V electrical cables and cables for data transmission remain valid, whereas other hypotheses seem to be invalidated by experience. The fact that for example electric devices are a constant factor in the appearance of L.s., that the cable type apparently plays an important role as well as the electric conductivity of the desktops on which L.s. subjects are sitting and that the presence of ionisators and the ambient relative humidity also proved to be determinative are arguments that the electric environment is on the origin of the L.s. condition. However, evidence was obtained that L.s. is most probably not related to electrostatic discharges but other phenomena of electro-stimulation are nevertheless possible. For example, formation of atmospheric air ions at the edge of the desk or on dust particles on their surface and consequently charging of the skin followed by discharges in the skin may be proposed as the main cause of L. semicircularis. This means that it is essential to control the electric environment of offices to minimize the risk of L. semicircularis.

FDG PET for monitoring response to local and locoregional therapy in HCC and liver metastases.

UNLABELLED: Local ablative therapies and loco-regional therapies are being increasingly used for the purpose of providing local control of primary liver tumors and liver metastases while sparing normal liver tissue. In this manuscript, literature on the use of fluorodeoxyglucose positron emission tomography (FDG PET) to monitor local and loco-regional treatment for hepatocellular carcinoma (HCC) and liver metastases, mainly limited to radiofrequency ablation (RFA) and selective internal radiation therapy (SIRT) is reviewed. Available data obtained primarily in secondary liver tumors and to a lesser extent in HCC support the notion that FDG PET performed early after RFA provides additional information about the efficacy of local tumor ablation by differentiating post-treatment changes from residual or recurrent malignant tumor. In addition, FDG PET was shown to have an added value for the detection of tumor recurrence. Thus, FDG PET imaging may not only improve treatment evaluation but also provide an opportunity for early re-intervention following RFA. Potential problems that might occur when using FDG PET for the purpose of evaluation of RFA are false negative results due to partial volume effect when dealing with small lesions (<1 cm) or due to diabetes and false positive results due to abscess formation. Larger studies are warranted to confirm these promising RESULTS: With regard to SIRT, several studies, almost exclusively performed in patients suffering from liver metastases, have addressed the feasibility of using FDG PET for the assessment and quantification of metabolic response of SIRT with (90)Y-microspheres. These studies consistently show that traditional morphological imaging, computed tomography/magnetic resonance imaging, is insensitive in monitoring response, owing to the presence of necrosis, edema, hemorrhage and cystic changes, when compared to metabolic imaging. Thus, in view of the lack of reliability of tumor markers and/or the potential for delineating the presence of extra-hepatic metastatic cancers in these patients, when confirmed by additional studies, FDG PET may prove to be an excellent adjunct for assessing response following SIRT of liver metastases.

Effect of different durations of ketoconazole dosing on the single-dose pharmacokinetics of midazolam: shortening the paradigm.

Given the prominent role of cytochrome P450 3A (CYP3A) in the metabolism of drugs, it is critical to determine whether new chemical entities will be affected by the inhibition of this enzyme system and result in clinically relevant drug interactions. Ketoconazole interaction studies are frequently performed to determine a given compound's sensitivity to CYP3A metabolism. The present study evaluated whether probing a sensitive substrate (midazolam) with a potent inhibitor (ketoconazole) at earlier time points (days 1 or 2) might be used to reliably gauge the magnitude of a meaningful interaction. The geometric mean ratios (ketoconazole+midazolamday 5/ketoconazole+midazolamday 1 and ketoconazole+midazolamday 5/ketoconazole+midazolamday 2) for midazolam AUC0-infinity were 1.36 and 1.06 with corresponding 90% confidence intervals of (1.17, 1.57) and (0.83, 1.23), respectively. These findings suggest that short-term drug-drug interaction studies can predict the magnitude of change in AUC as reliably as studies using longer duration treatments.