A high-density SNP linkage scan with 142 combined subtype ADHD sib pairs identifies linkage regions on chromosomes 9 and 16

As part of the International Multi-centre ADHD Genetics project we completed an affected sibling pair study of 142 narrowly defined Diagnostic and Statistical Manual of Mental Disorders, fourth edition combined type attention deficit hyperactivity disorder (ADHD) proband-sibling pairs. No linkage was observed on the most established ADHD-linked genomic regions of 5p and 17p. We found suggestive linkage signals on chromosomes 9 and 16, respectively, with the highest multipoint nonparametric linkage signal on chromosome 16q23 at 99 cM (log of the odds, LOD=3.1) overlapping data published from the previous UCLA (University of California, Los Angeles) (LOD>1, approximately 95 cM) and Dutch (LOD>1, approximately 100 cM) studies. The second highest peak in this study was on chromosome 9q22 at 90 cM (LOD=2.13); both the previous UCLA and German studies also found some evidence of linkage at almost the same location (UCLA LOD=1.45 at 93 cM; German LOD=0.68 at 100 cM). The overlap of these two main peaks with previous findings suggests that loci linked to ADHD may lie within these regions. Meta-analysis or reanalysis of the raw data of all the available ADHD linkage scan data may help to clarify whether these represent true linked loci.     

Prof. Dr. Heinz Flegel zum 80. Geburtstag

Ohne Zusammenfassung     

MRI of the pharynx and treatment efficacy of a mandibular advancement device in obstructive sleep apnoea syndrome.

In obstructive sleep apnoea syndrome (OSAS), prosthetic mandibular advancement devices (MAD) seem to be a promising treatment alternative to conventional continuous positive airway pressure therapy. Unfortunately, while they are effective in some patients, they are ineffective in others or may even worsen OSAS. At present, it is not known whether predictors can be defined which allow for estimation of the potential effect of oral appliances on the severity of OSAS. Clinical and polysomnographical efficacy of a MAD was evaluated in 15 patients with OSAS. In addition, ultrafast magnetic resonance imaging (MRI) of the pharynx was performed in 13 of these patients at rest during transnasal shallow respiration and during performance of the Muller manoeuvre, both with and without the MAD, and the site of closure was determined. The MAD reduced the mean apnoea/hypopnoea index (AHI) from 19.8+/-14.5 to 7.2+/-7.4 x h(-1). Seven subjects (53.8%) had at least a 50% reduction in AHI to a value <10 x h(-1) with the MAD, whereas the MAD was ineffective in six patients. Five of the seven treatment responders had no significant pharyngeal obstruction during the manoeuvre with the device, while all of them had pharyngeal obstruction when not equipped with the device. Four of the six patients with treatment failure had a single velopharyngeal obstruction and two a combined obstruction of the velo- and glossopharynx during the Muller manoeuvre while wearing the device. The results of this study suggest that airway patency during the Muller manoeuvre while wearing a mandibular advancement device may be predictive of the success of obstructive sleep apnoea syndrome treatment with a mandibular advancement device.     

Mesenterialarterienverschluss als seltene Komplikation bei Thrombangiitis obliterans

Mesenteric artery occlusions are rare complications of Thrombangiitis obliterans (Buerger's disease). We report on a 30-year old male with Thrombangiitis obliterans and mesenteric occlusion as a complication of this disease. Because of unclear abdominal pain, laparoscopy was performed which showed small bowel infarction and reduced liver perfusion. After small bowel resection and a second examination, ischemia of the intestinum continued. Angiography was performed, which showed central occlusion of the celiac trunk and the superior mesenteric artery. Relaparotomy with the embolectomy of the superior mesenteric artery, venous bypass from the sup.mes.art. to the hepatic arteries and repeated small bowel resection was performed. The patient recovered completely and was discharged from hospital after 3 weeks. After a further admission to the hospital 3 weeks later with abdominal pain caused by acute occlusion of the right colonic artery and severe ischemia of the right hemicolon, a right hemicolectomy was performed.Now, one year after the last hospital admission, the patient shows no sign of having any abdominal problems.     

Reflectance spectroscopy can quantify cutaneous haemoglobin oxygenation by oxygen uptake from the atmosphere after epidermal barrier disruption

Background: The supply of oxygen to the viable skin tissue within the upper layers is not only secured by the cutaneous blood vascular system, but to a significant part also by oxygen diffusion from the atmosphere through the horny layer. The aim of this study was to examine whether changes in haemoglobin oxygenation can be observed within the isolated perfused bovine udder skin used as a skin model by removing the upper horny layer by adhesive tape stripping.
Methods: Diffuse reflectance spectroscopy in the visible spectral range was used for non-invasive characterisation of haemoglobin oxygenation in skin under in vitro conditions. Mid-infrared attenuated total reflectance spectroscopy was employed for analysing the surface layer of the stratum corneum with respect to keratin, water and lipid components. Skin barrier disruption was achieved by repeated stripping of superficial corneocyte layers by adhesive tape.
Results and conclusion: Significant changes in skin haemoglobin oxygenation were observed for skin areas with reduced lipid concentration and a reduced stratum corneum layer, as determined from the quantitative evaluation of the diffuse reflectance skin spectra. The result can be interpreted as an increase of oxygen diffusion after the removal of the upper horny layer.     

Incidence of temporomandibular joint symptoms following whiplash injury.

Recently there has been considerable litigation involving the development of temporomandibular joint (TMJ) pain and dysfunction following cervical musculoskeletal injury (whiplash). The purpose of this investigation was to interview, examine, and follow up patients with a diagnosis of whiplash injury to determine the incidence of associated temporomandibular disorders. Patients were divided into two categories: those with and those without radiologic evidence of cervical skeletal injury. In the 63 patients with radiographic evidence of cervical skeletal injury (group 1), none had clicking at the time of initial examination. In the 92 patients without positive radiographs (group 2), only one had clicking. At 1 month follow-up by telephone, 2 of 51 available patients in group 1 had developed clicking, but no new TMJ symptoms were reported by the 78 patients in group 2 contacted by phone. Seventy percent of the initial follow-up group (44 patients) with radiographic evidence of injury were contacted by telephone at 1 year and none reported new symptoms of TMJ pain or clicking. Sixty-five percent of the initial follow-up group without radiographic evidence of injury (60 patients) were interviewed and also reported no new TMJ symptoms. These data indicate that the incidence of TMJ pain and clicking following whiplash injury is extremely low, and that patients who do not have clicking on resolution of their initial pain/dysfunction subsequently do not develop this problem.     

15The effect of Lower Esophageal Sphincter (LES) electrical stimulation on LES pressure

Background: Electrical stimulation (ES) of the stomach has been shown to modulate LESP. Electrical stimulation, using neural high frequency stimulation (NGES) can induce contractions of the smooth muscle of the gut. The purpose of this study was to determine if electrical stimulation of the LES can affect LESP. Methods: Four female hound dogs, weight: 20–25 kg, underwent an esophagostomy that allowed the introduction of a sleeve manometry catheter into the esophagus. They were also implanted with a pair of electrodes along the longitudinal axis of the LES. After 3 weeks of recovery, they underwent esophageal manometry recording during control and ES, performed randomly on separate days, using 4 different stimulations: 1‐Low frequency: freq: 6 cycles/min, pulse: 350 milisec, amp: 5 mAmp; 2 High‐frequency: freq: 50 Hz, pulse: 1 milisec, amp: 5 mAmp; 3‐ NGES: freq: 50 Hz, pulse:20 milisec, amp:10 volts; 4‐ High‐frequency, circular: freq: 20 Hz, pulse:1 milisec, amp:5 mAmp. All recordings were performed 1 hour after consumption of 3 ounces of canned dog food, to prevent fluctuations in LESP and under mild sedation (acepromazine 0.5 mg kg^­1). Tests consisted, during ES days, of 3 periods of 20 minutes each: control , stimulation and post stimulation. The effect of NGES was also tested under anesthesia and following administration of L‐NAME 50 mg kg^­1 IV. and also atropine 0.05 mg kg^­1 IV. Analysis: area under the curve (AUC) and pressure were compared among the 3 periods. Data shown as mean ± SD, ANOVA and t‐test, p < 0.05. Results: Sustained increase in LESP was observed during low frequency stimulation, 32.1 ± 12.8 vs. 42.4 ± 18.0 vs. 50.1 ± 23.6, control vs. stimulation vs. post stimulation respectively, p = 0.013. AUC also significantly increased during and after stimulation, 39,320.3 ± 15,722 vs. 51,294 ± 21,826 vs. 59,823.6 ± 28,198.4 mmHgxsec, control vs. stimulation vs. post stimulation respectively, p = 0.01. There was no significant change with other types of ES. NGES induced an initial rise in LESP followed within few seconds by relaxation with slow resumption of pressure over a 1 minute period. L‐NAME increased LESP and augmented the initial rise in LESP following NGES but markedly diminished or abolished the relaxation phase. Atropine lowered LESP and abolished the initial rise in LESP induced by NGES. Conclusions: Low frequency ES of the LES increases LESP in conscious dogs. NGES has dual effect on LESP: an initial stimulation, cholinergically mediated, followed by relaxation mediated by nitric oxide.     

Mesenterialarterienverschluss als seltene Komplikation bei Thrombangiitis obliterans

Mesenterialarterienverschlüsse sind eine seltene Komplikation der Thrombangiitis obliterans. Wir berichten über einen 30-j?hrigen Patienten mit einer Thrombangiitis obliterans und einem Mesenterialarterienverschluss als Komplikation dieser Erkrankung. Bei unklaren abdominellen Schmerzen wurden im Rahmen einer Laparoskopie ein Dünndarminfarkt und eine Minderperfusion der Leber bei dem Patienten diagnostiziert, sodass zun?chst eine Dünndarmteilresektion durchgeführt werden musste. Bei weiterhin bestehender Dünndarmisch?mie erfolgte dann eine Angiographie, die einen zentralen Verschluss des Truncus coeliacus und der A. mesenterica superior zeigte. Daraufhin wurde der Pat. relaparotomiert, die A. mesenterica superior embolektomiert, ein Venenbypass von der A. mesenterica superior zu beiden Leberarterien gelegt und eine erneute Dünndarmteilresektion durchgeführt. Nach initial unauff?lligem Verlauf und Entlassung wurde der Patient bei erneuter abdomineller Symptomatik 3 Wochen sp?ter wieder station?r aufgenommen und aufgrund eines akuten Verschlusses der A. colica dextra eine Hemikolektomie rechts durchgeführt. Seit einem Jahr ist bei dem Patienten keine abdominelle Symptomatik im Rahmen seiner Erkrankung mehr aufgetreten.     

Safety trial with the 5HT1B/1D agonist avitriptan (BMS-180048) in patients with migraine who have experienced pressure, tightness, and/or pain in the chest, neck, and/or throat following sumatriptan

We investigate whether symptoms of pressure, tightness, and/or pain in the chest, neck, and/or throat after administration of the 5HT_1B/1D agonist avitriptan were associated with objective impairment of the myocardial function on 12-lead electrocardiogram (ECG), continuous ECG (Holter) monitoring, and echocardiography. Migraine sufferers who in two-thirds of alt attacks treated with sumatriptan had experienced chest/throat/neck symptoms were chosen for study. Baseline measures included vital signs, a 12-lead ECG and an echocardiogram. Patients ( n =51) who had no clinically significant abnormality at baseline received a high dose (150 mg) of avitriptan orally outside of a migraine attack. If pressure, tightness, and/or pain in the chest, neck, and/or throat occurred, an ECG was obtained, and a repeat echocardiogram was done while the symptoms were present in order to monitor for impairment of myocardial function. If symptoms of these types did not occur within 60 min after administration of the study drug, a second echocardiogram was obtained. Forty-five patients (88%) reported at least one adverse event and 23 (45%) experienced pressure, tightness, and/or pain in the chest, neck, and/or throat after administration of avitriptan. No clinically significant myocardial abnormalities were observed in any patient, even in those who had experienced the targeted symptoms. No other serious adverse event occurred. We concluded that the typical 5HT_1B/1D agonist-induced chest/throat/neck symptoms are most unlikely to be of cardiovascular origin.     

Efficacy of confrontational counselling for smoking cessation in smokers with previously undiagnosed mild to moderate airflow limitation: study protocol of a randomized controlled trial

Background  

The use of spirometry for early detection of chronic obstructive pulmonary disease (COPD) is still an issue of debate, particularly because of a lack of convincing evidence that spirometry has an added positive effect on smoking cessation. We hypothesise that early detection of COPD and confrontation with spirometry for smoking cessation may be effective when applying an approach we have termed "confrontational counselling"; a patient-centred approach which involves specific communication skills and elements of cognitive therapy. An important aspect is to confront the smoker with his/her airflow limitation during the counselling sessions. The primary objective of this study is to test the efficacy of confrontational counselling in comparison to regular health education and promotion for smoking cessation delivered by specialized respiratory nurses in current smokers with previously undiagnosed mild to moderate airflow limitation.