Opioid analgesic effects on subjective well-being in the operating theatre.

Exposure to opioid analgesics due to surgery increases the risk of new persistent opioid use. A mechanistic hypothesis for opioids' abuse liability rests on the belief that, in addition to pain relief, acute opioid treatment improves well-being (e.g. via euphoria) and relieves anxiety. However, opioids do not consistently improve mood in laboratory studies of healthy non-opioid users. This observational study determined how two commonly used opioid analgesics affected patients' subjective well-being in standard clinical practice. Day surgery patients rated how good and how anxious they felt before and after an open-label infusion of remifentanil (n = 159) or oxycodone (n = 110) in the operating theatre before general anaesthesia. One minute after drug injection, patients reported feeling intoxicated (> 6/10 points). Anxiety was reduced after opioids, but this anxiolytic effect was modest (remifentanil Cohen's d = 0.21; oxycodone d = 0.31). There was moderate to strong evidence against a concurrent improvement in well-being (Bayes factors > 6). After remifentanil, ratings of 'feeling good' were significantly reduced from pre-drug ratings (d = 0.28). After oxycodone, one in three participants felt better than pre-drug. Exploratory ordered logistic regressions revealed a link between previous opioid exposure and opioid effects on well-being, as only 14 of the 80 opioid-naïve patients reported feeling better after opioid injection. The odds of improved well-being ratings after opioids were higher in patients with previous opioid exposure and highest in patients with > 2 weeks previous opioid use (adjusted OR = 4.4). These data suggest that opioid-induced improvement of well-being is infrequent in opioid-naïve patients. We speculate that peri-operative exposure could increase risk of persistent use by rendering subsequent positive opioid effects on well-being more likely.

[Hospital disaster planning in south-western Germany. A survey of 214 clinics]. / Krankenhausalarm- und -einsatzplanung in Baden-Württemberg. Eine länderspezifische Umfrage an 214 Kliniken.

Background: Due to legal regulations in Germany, public acute and emergency (A&E) hospitals-along with responsible authorities, emergency medical services, and other institutions such as the state medical associations-are committed to participate in civil protection. This participation includes the need to create and update emergency plans for external and internal crises and to take part in disaster drills. In fact, so far there is only little literature to prove whether and to what extent hospitals fulfill their obligations on this topic. Objectives: Using a standardized survey, the state of emergency planning in hospitals in Baden-Wuerttemberg was evaluated. Materials and methods: Based on a listing provided by the Hospital Society of Baden-Wuerttemberg (BWKG), all 214 hospitals in Baden-Wuerttemberg were identified. The standardized questionnaire inquired about specific characteristics of the emergency plan, the availability and knowledge of this plan by the hospital workforce and other local institutions that take part in civil protection and, finally, participation in disaster drills were queried. Results: Of the 214 hospitals in Baden-Wuerttemberg, 135 (63%) provided information using the questionnaire. Except for one hospital, all other clinics indicated having a special emergency plan ready. In most cases (79.3%), both external (e.g., mass casualty incidents) and internal (e.g., fire, failure of technical equipment) crises are covered. In the vast majority of cases (94%), the hospitals also indicated that they regularly update their emergency plan, whereby the frequency of updates varied markedly. Three quarters of the hospitals said that they also regularly simulate the use of the emergency plan in disaster drills. In two thirds of the cases, external forces such as emergency medical services or the fire department also take part in these drills along with the hospitals themselves. In some cases, knowledge gained from the drills was incorporated into the emergency plan or led to improvements in staff training. Conclusions: The willingness of public hospitals to establish comprehensive disaster planning and to take part in related drills seems to have improved noticeably in recent years. However, there is still the need for improvement in keeping the concepts up to date at some hospitals. Especially smaller hospitals showed deficits in emergency planning, particularly concerning preparedness for internal crises, resulting from failure of technical equipment. More regular drills should be used to test existing concepts and to familiarize employees with the processes on a routine basis.

[Managing the pandemic-relocation concept for COVID-19 intensive care patients and non-COVID-19 intensive care patients in Baden-Württemberg]. / Die Pandemie bewältigen ­ Verlegungskonzept von COVID-19-Intensivpatienten und Non-COVID-19-Intensivpatienten in Baden-Württemberg.

BACKGROUND: A sharp rise in COVID-19 infections threatened to lead to a local overload of intensive care units in autumn 2020. To prevent this scenario a nationwide relocation concept was developed. METHODS: For the development of the concept publicly available infection rates of the leading infection authority in Germany were used. Within this concept six medical care regions (clusters) were designed around a center of maximum intensive care (ECMO option) based on the number of intensive care beds per 100,000 inhabitants. The concept describes the management structure including a structural chart, the individual tasks, the organization and the cluster assignment of the clinics. The transfers of intensive care patients within and between the clusters were recorded from 11 December 2020 to 31 January 2021. RESULT: In Germany and Baden-Württemberg, 1.5% of patients newly infected with SARS-CoV­2 required intensive care treatment in mid-December 2020. With a 7-day incidence of 192 new infections in Germany, the hospitalization rate was 10% and 28-35% of the intensive care beds were occupied by COVID-19 patients. Only 16.8% of the intensive care beds were still available, in contrast to 35% in June 2020. The developed relocation concept has been in use in Baden-Württemberg starting from 10 December 2020. From then until 7 February 2021, a median of 24 ± 5/54 intensive care patients were transferred within the individual clusters, in total 154 intensive care patients. Between the clusters, a minimum of 1 and a maximum of 15 (median 12.5) patients were transferred, 21 intensive care patients were transferred to other federal states and 21 intensive care patients were admitted from these states. The total number of intensive care patients transferred was 261. CONCLUSION: If the number of infections with SARS-CoV­2 increases, a nationwide relocation concept for COVID-19 intensive care patients and non-COVID-19 intensive care patients should be installed at an early stage in order not to overwhelm the capacities of hospitals. Supply regions around a leading clinic with maximum intensive care options are to be defined with a central management that organizes the necessary relocations in cooperation with regional and superregional rescue service control centers. With this concept and the intensive care transports carried out, it was possible to effectively prevent the overload of individual clinics with COVID-19 patients in Baden-Württemberg. Due to that an almost unchanged number of patients requiring regular intensive care could be treated.

[Assessment of the risk of infection from SARS-CoV-2 for healthcare workers-findings from practice]. / Beurteilung des Infektionsrisikos durch SARS-CoV-2 für medizinisches Personal ­ Erkenntnisse aus der Praxis.

SARS-CoV­2 has rapidly spread over the world in a pandemic manner causing an infection of predominantly pulmonary manifestation named the COVID-19 disease. Currently, there is neither an effective vaccination nor a specific therapy available. At least two vaccines will be available at the time of publication. In the international press, the risk for medical personnel of SARS-CoV­2 is rated as high. The Robert Koch Institute, Germany's leading epidemiological authority, regards the risk of infection for the general population to be high. The aim of this article is to discuss and reassess the risk of infection and disease for healthcare workers based on practical experience, national regulations and guidelines, and the number of infections. Both unprotected healthcare workers and healthcare workers equipped with personal protective equipment (PPE) are considered. A corresponding risk matrix is created.The risk of infection with SAR-CoV­2 for healthcare workers is comparable to the general population and rated as high. Proper use of PPE reduces this risk to medium. PPE consists of liquid-proof gowns, gloves, and filtering face pieces (FFP; FFP 2 as a standard, FFP 3 for aerosol-releasing interventions), a hair cover, and protective goggles. Improper use of PPE, inadequate hygienic measures, and long working shifts increase the risk of infection.

Moderating effect of occupational stress on spirituality and depression of Registered Nurses in tertiary hospital: A structural equation model.

AIM: The aim of this study was to determine the influence of spirituality to depression and to determine the moderating effect of occupational stress among Registered Nurses. BACKGROUND: Depression is a major contributor to the global burden of disease and it is influenced by several factors. Spirituality can be a protective factor against depression. However, it remains underexplored among nurses who experience several precipitating factors of depression, including occupational stress. DESIGN: Cross-sectional, predictive-correlational study. METHODS: From August - December 2017, 242 purposively selected nurses from selected tertiary hospitals completed a four-part survey packet composed of the "robotfoto," Spirituality Assessment Scale, Expanded Nursing Stress Scale, and Beck's Depression Inventory-II. Structural equation modelling analysed the influence of spirituality to depression, while multigroup analysis determined the moderating effect of occupational stress. RESULTS: "Personal faith, spiritual contentment, and religious practice" negatively influenced depression, generating a good model. Occupational stress significantly moderated the influence of spirituality to depression, with a significant inverse U-shaped effect for both "personal faith" and "religious practice" and a non-significant decreasing effect for "spiritual contentment". CONCLUSION: The stress-moderated model of the influence of spirituality to depression highlights three significant points. First, there is a need to develop individualized, spiritually based interventions based on the spiritual needs of Registered Nurses. Second, policies geared towards positive spirituality in the workplace and spiritual support to nurses must be explored. Finally, nurse managers must identify the sources of occupational stress and implement stress-reducing programmes in the workplace.

Difference between apnea-hypopnea index (AHI) and oxygen desaturation index (ODI): proportional increase associated with degree of obesity.

PURPOSE: Obesity is one of the main predisposing factors for obstructive sleep apnea (OSA) hypopnea syndrome. It has been described that body mass index (BMI) influences the accuracy of oxygen desaturation index (ODI) for the diagnosis of OSA by polysomnography (PSG). We analyzed the relationship between traditional indicators: apnea-hypopnea index (AHI) and ODI in a population at high risk for OSA, by respiratory polygraphy (RP) and PSG. METHODS: This is a retrospective study of 1898 patients with suspicion of OSA, from which 1053 underwent RP and 582 underwent PSG with OSA. We compared results considering gender, age, and degree of obesity. RESULTS: This study included 1333 records of patients with OSA-more than 80 % of whom were overweight or obese. We observed that AHI and ODI increased progressively with obesity grade and said increase was associated with BMI only in men. The evaluation of the agreement between AHI and ODI found a difference between normal weight and obese patients, regardless of gender. CONCLUSIONS: Study findings contribute to understand the role of oximetry in the diagnosis of OSA in obese patients. Our results were observed using full PSG and a simplified home method. The correlation between these indicators could improve our clinical interpretation of OSA severity among obese patients when abbreviated tests are used.

DNA methyltransferases: mechanistic models derived from kinetic analysis.

The sequence-specific transfer of methyl groups from donor S-adenosyl-L-methionine (AdoMet) to certain positions of DNA-adenine or -cytosine residues by DNA methyltransferases (MTases) is a major form of epigenetic modification. It is virtually ubiquitous, except for some notable exceptions. Site-specific methylation can be regarded as a means to increase DNA information capacity and is involved in a large spectrum of biological processes. The importance of these functions necessitates a deeper understanding of the enzymatic mechanism(s) of DNA methylation. DNA MTases fall into one of two general classes; viz. amino-MTases and [C5-cytosine]-MTases. Amino-MTases, common in prokaryotes and lower eukaryotes, catalyze methylation of the exocyclic amino group of adenine ([N6-adenine]-MTase) or cytosine ([N4-cytosine]-MTase). In contrast, [C5-cytosine]-MTases methylate the cyclic carbon-5 atom of cytosine. Characteristics of DNA MTases are highly variable, differing in their affinity to their substrates or reaction products, their kinetic parameters, or other characteristics (order of substrate binding, rate limiting step in the overall reaction). It is not possible to present a unifying account of the published kinetic analyses of DNA methylation because different authors have used different substrate DNAs and/or reaction conditions. Nevertheless, it would be useful to describe those kinetic data and the mechanistic models that have been derived from them. Thus, this review considers in turn studies carried out with the most consistently and extensively investigated [N6-adenine]-, [N4-cytosine]- and [C5-cytosine]-DNA MTases.

DIY Flap Monitoring: The Glucose Index.

Background: Flap loss is reduced by monitoring, which detects vascular compromise. Glucose levels vary in suffering flaps; therefore, we aimed to show that monitoring flaps with glucose pinprick test is a cheap, reliable, ubiquitous, and easy method. Methods: We reviewed a prospectively kept database. A pinprick test was performed to measure systemic and flap glucose levels. A glucose index (GI; flap glucose/systemic glucose) was calculated. Comparison between the groups (with occlusive event, and without occlusive event) was done. Results: In total, 32 flaps in 29 consecutive patients were included. Eleven (34%) were free flaps. Of these, one (9%) was explored twice. Initially, salvage was achieved. However, 36 hours later, a second exploration was needed but was unsuccessful. Of the 21 pedicled flaps (66%), one (5%) needed exploration (suture release), and three (14%) had partial losses that were not clinically relevant. On the ROC curve, we found a cut-off value for a GI of 0.49 or less with a sensitivity of 95% [95% confidence interval (CI): 75.1 to 99.9%] and a specificity of 100% (95% CI: 98.5 to 100%), with a positive predictive value of 100% (95% CI: 81.5 to 100%) and a negative predictive value of 99.6% (95% CI: 97.8 to 100%) for flap suffering. Conclusions: The GI, as a complement, assists in defining treatment approach. It is an easy, reliable, accessible method that can be performed by nonmedical personnel. Its main drawback is the inability to monitor buried or hard to reach flaps.

[Fractionated inpatient rehabilitation of diabetes: results from a randomized controlled trial on rehabilitation aftercare]. / Intervallrehabilitation bei Diabetes mellitus: ergebnisse einer randomisierten kontrollierten Studie zur Nachsorge in der medizinischen Rehabilitation.

BACKGROUND: Treating diabetes mellitus type 2 (DMT2) essentially involves long-term changes of health behaviour, especially diet and physical activity habits. Medical rehabilitation tries to support these changes by patient education and practical instructions. While short-term successes are frequently obtained, the main challenge lies in maintaining these results in the longer run. This study examines whether a fractionated inpatient rehabilitation programme of 3 weeks duration in combination with an additional week of inpatient rehabilitation after 6 months and a subsequent aftercare telephone service facilitates positive long-term effects for patients with DMT2. METHOD: A prospective randomized controlled trial was conducted with 411 patients with DMT2 in order to compare the fractionated inpatient rehabilitation programme with aftercare to a 3-weeks standard rehabilitation programme without aftercare. The analysis included physiological (cardiovascular risk, HbA1c, BMI) and psychosocial (diabetes-specific coping, quality of life) parameters at baseline (beginning of the programme) and 1 year later. RESULTS: After 12 months, no significant differences between the groups were found in the physiological parameters. At the same time, however, the aftercare group showed larger benefits in almost every psychosocial dimension (coping, quality of life, subjective health). Coping and quality of life had even improved when compared to baseline. In contrast, these parameters had decreased further in the standard-care control group when compared to baseline. CONCLUSION: The intensive aftercare was successful in the long-term improvement of the patients' psychological well-being. Also, the high rate of participation in fractionated inpatient rehabilitation suggests both the acceptance of and the need for aftercare. However, positive long-term changes of physiological parameters probably will require more specific interventions or individual case management. The effectiveness of fractionated inpatient rehabilitation may be limited by the adverse social, psychological and financial situation of the patients.

[Development and validation of an inventory of ego functions and self regulation (Hannover Self-Regulation Inventory, HSRI)]. / Entwicklung und Validierung eines Fragebogens zu Ich-Funktionen und zur Selbstregulationsfähigkeit (Hannover-Selbstregulations-Inventar, HSRI).

OBJECTIVE: The aim of this study was to construct and validate a short self-rating questionnaire for the assessment of ego functions and ability of self regulation. MATERIAL AND METHODS: An item pool of 120 items covering 6 postulated dimensions was reduced by two steps in independent samples (n = 136 + 470) via factor and item analyses to the final version consisting of 35 items. RESULTS: The 5 resulting questionnaire scales "interpersonal disturbances", "frustration tolerance and impulse control", "identity disturbances", "affect differentiation and affect tolerance" and "self-esteem" were well interpretable and showed in confirmatory factor analysis the best fit to the data (CHI²/df = 3.48; RMSEA = 0.73). Total scores were found to differentiate well between diagnostic groups of patients with more or less ego pathology (FANOVA = 9.8; df = 11; p < 0.001), thus proving good concurrent validity. Reliability was shown by testing internal consistency and test-retest correlations. CONCLUSION: The "Hannover self-regulation questionnaire" (HSRQ) evidently is an appropriate and reliable screening instrument in order to assess ego functions and capacities of self regulation in an economic and user-friendly means. The scale structure allows differentiated diagnostics of weak vs. stable ego functions and may be used for detailed therapy planning.

Dimeric/oligomeric DNA methyltransferases: an unfinished story.

DNA methyltransferases (MTases) are enzymes that carry out post-replicative sequence-specific modifications. The initial experimental data on the structure and kinetic characteristics of the EcoRI MTase led to the paradigm that type II systems comprise dimeric endonucleases and monomeric MTases. In retrospect, this was logical because, while the biological substrate of the restriction endonuclease is two-fold symmetrical, the in vivo substrate for the MTase is generally hemi-methylated and, hence, inherently asymmetric. Thus, the paradigm was extended to include all DNA MTases except the more complex bifunctional type I and type III enzymes. Nevertheless, a gradual enlightenment grew over the last decade that has changed the accepted view on the structure of DNA MTases. These results necessitate a more complex view of the structure and function of these important enzymes.

Optimized 124I PET dosimetry protocol for radioiodine therapy of differentiated thyroid cancer.

UNLABELLED: Iodine kinetics and lesion dose per administered 131I activity (LDpA) of differentiated thyroid cancer metastases were determined using 124I PET. These data were analyzed to derive an optimized dosimetry protocol. METHODS: We evaluated the time-activity-concentration curves of 37 lesions in 17 patients who had undergone thyroidectomies. LDpA determination involved 124I PET images acquired at 4, 24, 48, 72, and 96 h after intake of a capsule containing 20-40 MBq of 124I. A combination of a linear and a monoexponential or a monoexponential function only parameterized the time-activity-concentration curves. The LDpAs, calculated using data from all 5 PET time points, served as reference. The lesions were classified into 3 groups, according to potential for cure with 131I therapy: low (< or =5 Gy GBq(-1); n = 14), medium (between 5 and 10 Gy GBq(-1); n = 9), or high LDpAs (>10 Gy GBq(-1); n = 14). Using the reference approach, the differences in the empiric kinetic parameters within the LDpA groups were evaluated. The reference LDpAs were compared with those derived from only 2, 3, or 4 PET data points and from 1 adapted 2-point approach. Lin's concordance correlation coefficient (rho c) and the mean absolute percentage deviation in LDpAs were used to assess agreement between simplified and reference approaches. RESULTS: The effective 124I half-life, linear activity-concentration rate (alpha), and 24-h activity concentration (CpA) (the latter 2 per administered 124I activity) differed significantly among the LDpA groups (P < 0.05). LDpAs correlated with 24-h CpAs (r = 0.94, P < 0.001). Using the 4-, 24-, and 96-h measurements, a rho c value of greater than or equal to 0.90 was found, and the mean absolute percentage deviation was less than or equal to 16%. Similar statistical values were obtained for the adapted approach, which was based on 24- and 96-h PET data points only. CONCLUSION: Lesion classification into LDpA groups was feasible using a single PET scan at approximately 24 h. Because of the highly variable kinetics, 1 additional measurement at approximately 96 h was needed to obtain a sufficiently reliable LDpA estimate. The adapted 24-96-h approach appears to be the optimal 124I protocol and is a reliable simplification of the 5-point protocol.

Influence of various geometric factors on the iodine-131 uptake measurement for solitary thyroid nodules.

AIM: The influence of various geometric factors on I uptake measurements for solitary thyroid nodule was systematically investigated to derive an approach, based on routinely performed ultrasound examinations, to correct for the effect of geometric variations. METHODS: The influence of size, shape, and position of a thyroid nodule, neck-to-detector distance and neck curvature on the uptake value was analyzed with a three-dimensional model. Uptake measurements using a tissue-equivalent neck phantom were carried out to verify the calculated correction factors and also to check the influence of scatter. Sonograms of 92 patients with solitary nodules were analyzed to correct for geometric variations. RESULTS: The correction factors were independent of the size and shape of the nodule, and the activity distribution of the solitary nodules can be approximated by a point source. The correction factors were mainly determined by the nodular depth and by the accuracy of the neck-to-detector distance and were affected to a lesser extent by the lateral position of the nodule as well as the curvature of the neck. The effect of scatter can be neglected if the energy window largely excludes Compton scatter, as is the case in the I uptake measurement. The ultrasound-derived correction factors ranged from 0.85 to 1.25. CONCLUSION: The proposed approach is capable of correcting for the geometric variation for a solitary nodule and can be easily applied in routine clinics. The accuracy of absorbed dose in radioiodine therapy can be improved in particular for nodules located well beneath the neck surface.

Seminal vesicle fluid increases the efficacy of intravaginal HSV-2 vaccination.

Once considered merely as a vehicle for spermatozoa, it is now clear that seminal plasma (SP) induces a variety of biological actions on the female reproductive tissues able to modulate the immune response against paternal antigens. To our knowledge, the influence of SP on the immune response against sexually transmitted pathogens has not been yet evaluated. We here analyzed whether the seminal vesicle fluid (SVF), which contributes almost 60% of the SP volume in mice, could modulate the immune response against herpes simplex virus type 2 (HSV-2). We found that SVF does not modify the course of primary infection, but markedly improved protection conferred by vaginal vaccination with inactivated HSV-2 against a lethal challenge. This protective effect was shown to be associated to a robust memory immune response mediated by CD4+ and CD8+ T cells in both the lymph nodes draining the vagina and the vaginal mucosa, the site of viral replication. In contrast with the widespread notion that SP acts as an immunosuppressive agent, our results suggest that SVF might improve the female immune response against sexually transmitted pathogens.

Universal characteristics of evolution and development are inherent in fetal autonomic brain maturation.

Adverse prenatal environmental influences to the developing fetus are associated with mental and cardiovascular disease in later life. Universal developmental characteristics such as self-organization, pattern formation, and adaptation in the growing information processing system have not yet been sufficiently analyzed with respect to description of normal fetal development and identification of developmental disturbances. Fetal heart rate patterns are the only non-invasive order parameter of the developing autonomic brain available with respect to the developing complex organ system. The objective of the present study was to investigate whether universal indices, known from evolution and phylogeny, describe the ontogenetic fetal development from 20 weeks of gestation onwards. By means of a 10-fold cross-validated data-driven multivariate regression modeling procedure, relevant indices of heart rate variability (HRV) were explored using 552 fetal heart rate recordings, each lasting over 30 min. We found that models which included HRV indices of increasing fluctuation amplitude, complexity and fractal long-range dependencies largely estimated the maturation age (coefficients of determination 0.61-0.66). Consideration of these characteristics in prenatal care may not only have implications for early identification of developmental disturbances, but also for the development of system-theory-based therapeutic strategies.

Segmentation of PET volumes by iterative image thresholding.

UNLABELLED: The segmentation of metastatic volumes in PET is usually performed by thresholding methods. In a clinical application, the optimum threshold obtained from the adaptive thresholding method requires a priori estimation of the lesion volume from anatomic images such as CT. We describe an iterative thresholding method (ITM) used to estimate the PET volumes without anatomic a priori knowledge and its application to clinical images. METHODS: The ITM is based on threshold-volume curves at varying source-to-background (S/B) ratio acquired from a body phantom. The spheres and background were filled either with (18)F-FDG or Na(124)I ((124)I). These calibrated S/B-threshold-volume curves were used in estimating the volume by applying an iterative procedure. The ITM was validated with a PET phantom containing spheres and with 39 PET tumors that were discernable on CT by using whole-body (18)F-FDG (15 patients) and (124)I PET/CT (9 patients): The measured S/B ratios of the lesions were estimated from PET images, and their volumes were iteratively calculated using the calibrated S/B-threshold-volume curves. The resulting PET volumes were then compared with the known sphere inner volume and CT volumes of tumors that served as gold standards. RESULTS: Phantom data analysis showed that the S/B-threshold-volume curves of (18)F-FDG and (124)I were similar. The average absolute deviation (expressed as a percentage of the expected volume) obtained in the PET validation phantom was 10% for volumes larger than 1.0 mL; sphere volumes of 0.5 mL showed a significantly larger deviation. For patients, the average absolute deviation for volumes between 0.8 and 7.5 mL was about 9% (31 lesions), whereas volumes larger than 7.5 mL showed an average volume mismatch of 15% (8 lesions). CONCLUSION: The ITM sufficiently estimated the clinical volumes in the range of 0.8-7.5 mL; volumes larger than 7.5 mL showed greater deviations that were still acceptable. These findings are associated with the limitation of the ITM. The ITM is especially useful for lesions that are only visible on PET. As a consequence, the lesion dosimetry is feasible with sufficient accuracy using PET images only.

Cortisol as a possible marker of metastatic adrenocortical carcinoma: a case report with 3-year follow-up.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare tumour, sometimes causing glucocorticoid hypersecretion. Treatment guidelines have not been established, but are currently under investigation. CASE REPORT: A 55-year-old Caucasian woman presented with adrenal Cushing's disease. Histological examination after a left adrenalectomy revealed a benign tumour. Postoperatively, elevated serum cortisol levels normalized. Hypercortisolism occurred again two years later. Diagnostic work-up revealed hepatic metastatic lesions of an ACC which were treated by right hemihepatectomy. Initial histological diagnosis was revised according to the increased proliferative changes. Postoperatively, cortisol declined to normal levels. Treatment with mitotane (o, p'-DDD) as a cytostatic agent was not tolerated. One year later, the patient was diagnosed with a solitary osseous metastasis at the left side of the sacrum because of back pain. Following curettage and stabilization, radiotherapy of this region with 37.5 Gy was performed, improving slightly elevated cortisol levels and neurological symptoms. CONCLUSION: Careful clinical and radiographic follow-up of patients with ACC are important. In this case of oligometastasizing ACC, serum cortisol values correlated with the clinical course. An aggressive multimodal treatment, including repeated surgical approach with consolidating radiotherapy in cases of incomplete resection, might be indicated to provide symptom control and possible long-term survival in oligometastatic disease of ACC.

Relationship between cumulative radiation dose and salivary gland uptake associated with radioiodine therapy of thyroid cancer.

AIM: To estimate the individual absorbed dose to the parotid and submandibular salivary glands in radioiodine therapy and its dependence from the previous cumulative therapy. METHODS: Fifty-five patients with differentiated thyroid carcinoma after thyroidectomy received 1-21 GBq (131)I using single activities of 1-6 GBq. The patients were stratified according to the cumulative activities into low-activity (1-2 GBq), middle-activity (3-7 GBq), and high-activity groups (9-21 GBq). The time-activity curves over the respective salivary glands were derived from multiple static calibrated images measured for each patient up to 48 h after ingestion of the radioiodine therapy capsule with a gamma camera. Manually drawn regions of interests were used to determine the background activities and the activities arising from the salivary glands. The gland volumes were determined by ultrasonography using appropriate volume models. RESULTS: The median absorbed dose per administered activity of each single parotid and submandibular gland was about 0.15 Gy.GBq (range, 0.1-0.3 Gy.GBq(-1)) and 0.48 Gy.GBq(-1) (range, 0.2-1.2 Gy.GBq(-1)), respectively. The maximum uptake of both gland types was significantly lower for the high-activity than for the low-activity groups and correlated with the mean cumulative administered activity of the activity groups. CONCLUSION: The iodine uptake of salivary glands is significantly reduced, whereas the absorbed dose per administered (131)I activity was not significantly decreased during the course of therapy. Comparing the well-known dose-effect relationships in external radiation therapy, the absorbed dose per administered (131)I activity is too low to induce comparable radiation damage, suggesting an inhomogeneous distribution of (131)I in human salivary glands.

Symmetry elements in DNA structure important for recognition/methylation by DNA [amino]-methyltransferases.

The phage T4Dam and EcoDam DNA-[adenine-N6] methyltransferases (MTases) methylate GATC palindromic sequences, while the BamHI DNA-[cytosine-N4] MTase methylates the GGATCC palindrome (which contains GATC) at the internal cytosine residue. We compared the ability of these enzymes to interact productively with defective duplexes in which individual elements were deleted on one chain. A sharp decrease in kcat was observed for all three enzymes if a particular element of structural symmetry was disrupted. For the BamHI MTase, integrity of the ATCC was critical, while an intact GAT sequence was necessary for the activity of T4Dam, and an intact GA was necessary for EcoDam. Theoretical alignment of the region of best contacts between the protein and DNA showed that in the case of a palindromic interaction site, a zone covering the 5'-symmetric residues is located in the major groove versus a zone of contact covering the 3'-symmetric residues in the minor groove. Our data fit a simple rule of thumb that the most important contacts are aligned around the methylation target base: if the target base is in the 5' half of the palindrome, the interaction between the enzyme and the DNA occurs mainly in the major groove; if it is in the 3' half, the interaction occurs mainly in the minor groove.