Rostral anterior cingulate cortex activity in the theta band predicts response to antidepressive medication.

During the last 10 years the knowledge about rostral anterior cingulate cortex (ACC) activity in major depression has substantially increased. Several groups have independently described a relationship between resting activity in this area and response to antidepressant treatment. We have recently confirmed a relationship between resting activity of rostral ACC activity and response in a group of 20 patients with major depression using resting theta activity. In this earlier study regions of interest (ROI) were defined in order to establish regional specificity. Differences between responders and nonresponders were only found in the ACC-ROI, but not in the posterior cingulate region. We have now reanalyzed our data using a whole brain voxelwise approach, in order not to miss any other relevant functional differences. In addition to major differences between responders and nonresponders in the rostral ACC, we have identified a nearby region in the midline orbito-frontal region.     

Radiusköpfchenfrakturen

Trauma und Berufskrankheit - Zusammenfassung Die angemessene Behandlung der Radiusköpfchenfrakturen erfolgt nach korrekter Klassifikation unter Berücksichtigung von Begleitverletzungen...     

Intimal hyperplasia and coronary flow reserve after heart transplantation: association with big endothelin-1

BACKGROUND: Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS: Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS: Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS: Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation.     

Modelling Germline Mosaicism and Different New Mutation Rates Simultaneously for Appropriate Risk Calculations in Families with Duchenne Muscular Dystrophy

For several genetic diseases two biological phenomena have been recognised as important: germline mosaicism; and different new mutation rates in males and females depending on mutation type. Both principles have been investigated separately and their influence on risk estimation in families has been exemplified in the literature. The aim of this paper is to present a general model that includes mosaicism and different new mutation rates. Mosaicism is introduced by defining additional alleles at the disease locus in combination with adapted segregation rules. Taking Duchenne muscular dystrophy as an example, we derive the conditions which have to be fulfilled for a population in mutation selection equilibrium. Our approach describes the model at the population level and not in individual subjects. This has the advantage of being able to use well known algorithms for the calculation of likelihoods in pedigrees, and to include additional diagnostic information such as marker genotypes and carrier deletion test results. We demonstrate the impact of the new model on a typical pedigree. In families where the patient is not available, the distinction between point mutations and deletions is important, since often molecular diagnostic tests for females can only screen for deletions. Negative deletion test results can now be included in the risk calculations.     

Reduced serotonin-1A receptor binding in social anxiety disorder.

BACKGROUND: Results from studies in serotonin-1A (5-HT1A) knockout mice and previous positron emission tomography (PET) studies in humans imply a role for 5-HT1A receptors in normal state anxiety as well as in certain anxiety disorders. The objective of this study was to investigate 5-HT1A receptor binding potential (BP) in social anxiety disorder (SAD). METHODS: Using PET and [carbonyl-11C]WAY-100635, we compared a homogeneous group of 12 unmedicated, male SAD patients with 18 healthy control subjects (HC). A multivariate ANOVA with all regional BP values as dependent variables, age and four radiochemical variables as covariates was performed. RESULTS: We found a significantly lower 5-HT1A BP in several limbic and paralimbic areas but not in the hippocampus (p = .234) of SAD patients. The difference in 5-HT1A binding was most significant in the amygdala (-21.4%; p = .003). There was also a more than 20% lower 5-HT(1A) BP of SAD patients in the anterior cingulate cortex (p = .004), insula (p = .003), and dorsal raphe nuclei (p = .030). CONCLUSIONS: The lower 5-HT1A binding in the amygdala and mesiofrontal areas of SAD patients is consistent with 1) preclinical findings of elevated anxiety in 5-HT1A knockout mice, 2) a previous PET study in healthy volunteers showing an inverse correlation between 5-HT1A BP and state anxiety, and 3) another human PET study in patients with panic disorder showing reduced 5-HT1A binding, thus corroborating the potential validity of 5-HT1A receptors as targets in the treatment of human anxiety disorders.     

Sonographic evaluation of gallbladder kinetics: in vitro and in vivo comparison of different methods to assess gallbladder emptying.

In an in vitro study, 10 gallbladders of adult pigs and 6 gallbladders of lambs, all removed immediately after slaughtering, were stimulated in a water bath by electric means to induce active contraction. Gallbladder emptying was followed by ultrasonography employing five measurement procedures: (1) gallbladder width, (2) longitudinal planimetry, (3) transverse planimetry, (4) ellipsoid method, and (5) sum of cylinders method. In an in vivo investigation, gallbladder emptying of 30 volunteers (12 healthy subjects, 18 diabetics) was evaluated in the same way after ingestion of a fatty meal. Gallbladder width was found to be unsuitable to estimate the decrease in gallbladder volume due to a nonlinear relation of the parameters. Longitudinal planimetry tended to be less valid than transverse planimetry in assessing gallbladder volume reduction. The most valid estimation of gallbladder volume decreases was obtained by the two three-dimensional procedures. However, in neither in vitro nor in vivo could a significant difference between the sum of cylinders method and the ellipsoid method in determining relative volume reduction be established. We conclude that a three-dimensional measurement procedure should be used for valid assessments of gallbladder motility. However, according to our data there is no advantage in using the time-consuming sum of cylinders method compared to the simple ellipsoid method.     

Effectiveness and Prognostic Factors of Radiotherapy for Painful Plantar Heel Spurs

BACKGROUND AND PURPOSE: The efficacy of radiation treatment (RT) for plantar heel pain has been reported repeatedly. Yet, the results referring to the pain relief rate, to long-term effects and prognostic factors are not consistent. In this paper, the effectiveness (pain relief rate and long-term results) and prognostic factors of RT for plantar heel pain have been investigated. PATIENTS AND METHODS: From January 2000 to October 2000, 62 patients (73 heels) with painful plantar heel spurs and a minimum pain history of 3 months were treated and evaluated in a prospective study. Mean age was 54 years (range 28-84 years). All patients were treated with a total dose of 5 Gy in seven fractions (= one series), given twice a week at a single-dose sequence of 0.25-0.25-0.5-1.0-1.0-1.0-1.0 Gy (10-MV photons, source-skin distance [SSD] 100 cm, direct portal, field size 12 x 17 cm). The mean duration of heel pain before RT was 26 weeks (= 6.5 months; range 3-120 months). By means of a visual analog scale (VAS) the patients had to self-assess the quantity of their heel pain once before, three times during and four times after RT at a longterm median follow-up of 28 and 40 months. Additionally, the patients had to assess their mechanical heel stress extent during RT. Effectiveness was estimated according to the patients' judgment of pain reduction. RESULTS: A significant reduction of heel pain extent measured by VAS has been observed already during the RT series (before RT: 6.3 +/- 1.5 vs. 3.8 +/- 2.1 at the end of RT; p < 0.001). 6 weeks after RT (FU 1) pain reduction (> 20%) was achieved in 60 heels (82.3%; n = 73), in 64 heels (91.4%; n = 70) after a mean follow-up of 28 months (FU 2), and in 61 heels (89.7%; n = 68) after a mean follow-up of 40 months (FU 3), respectively. Sufficient pain relief (> 80% compared to initial extent) was observed in 18/73 heels (24.6%) at FU 1 (FU 2: 42/70; 60.0%; FU 3: 37/68; 54.4%), including 13/73 heels (17.8%) with complete pain relief (FU 2: 39/70; 55.7%; FU 3: 36/68; 52.9%). Partial improvement (50-80% pain reduction) was observed in 27/73 heels (37.0%) at FU 1 (FU 2: 14/70; 20.0%; FU 3: 15/68; 22.1%), and minor partial improvement (20-50% pain reduction) in 15/73 heels (20.5%) at FU 1 (FU 2: 8/70; 11.4%; FU 3: 9/68; 13.2%), respectively. No change was seen in 13/73 heels (17.8%) at FU 1 (FU 2: 6/70; 8.6%; FU 3: 7/68; 10.3%). Older patients (p = 0.04) and patients who avoided heel stress during the period of RT (p < 0.01) demonstrated a better short-term response (FU 1); both effects were lost 28 and 40 months after RT. Moreover, significant differences in the extent of heel pain reduction by RT were observed in dependence on previous pain duration (at FU 2-3). CONCLUSION: The results confirm the high efficacy of RT in painful plantar spur and add new aspects to formerly published data concerning the time course of changes in heel pain reduction. Pain relief can be expected during and shortly after RT. In addition, the initial success can be transformed into effective long-term results > 2 years after RT; however, further improvement is not to be expected. As a new prognostic factor, the reduction of mechanical heel stress during RT may ameliorate the short-term results, whereas short heel pain history improves the long-term results. Especially for older patients, RT should be taken into consideration as primary treatment.