Gingival tissue transcriptomes identify distinct periodontitis phenotypes.

The currently recognized principal forms of periodontitis-chronic and aggressive-lack an unequivocal, pathobiology-based foundation. We explored whether gingival tissue transcriptomes can serve as the basis for an alternative classification of periodontitis. We used cross-sectional whole-genome gene expression data from 241 gingival tissue biopsies obtained from sites with periodontal pathology in 120 systemically healthy nonsmokers with periodontitis, with available data on clinical periodontal status, subgingival microbial profiles, and serum IgG antibodies to periodontal microbiota. Adjusted model-based clustering of transcriptomic data using finite mixtures generated two distinct clusters of patients that did not align with the current classification of chronic and aggressive periodontitis. Differential expression profiles primarily related to cell proliferation in cluster 1 and to lymphocyte activation and unfolded protein responses in cluster 2. Patients in the two clusters did not differ with respect to age but presented with distinct phenotypes (statistically significantly different whole-mouth clinical measures of extent/severity, subgingival microbial burden by several species, and selected serum antibody responses). Patients in cluster 2 showed more extensive/severe disease and were more often male. The findings suggest that distinct gene expression signatures in pathologic gingival tissues translate into phenotypic differences and can provide a basis for a novel classification.

[Creation of a control group by matched pairs with GKV routine data for the evaluation of enrollment models]. / Bildung einer Kontrollgruppe mithilfe von Matched-Pairs auf Basis von GKV-Routinedaten zur prospektiven Evaluation von Einschreibemodellen.

BACKGROUND: Various study approaches can be considered for the investigation of the efficiency of enrollment models, like GP-centred health-care contract or disease management programmes. As an active and independent enrollment into care models is effected by the insured (self-selection), a randomisation cannot be applied. The matched pairs design - in which for every insured a control insured with comparable morbidity is selected - presents an alternative investigation method. A precondition is a model that describes appropriately the morbidity on the basis of available routine data. TARGET: The aim of this study was to develop a procedure that selects comparable insured persons on the basis of routine data of the statutory health-care funds. METHODS: Apart from age, gender, care status, insured status, days of disability, region, health insurance and belonging to an enrollment model, also ambulant as well as stationary performance data for the year 2005 following the PCG/DCG procedure for morbidity-oriented matching design developed by Lamers and Vliet (2003) were applied. Thereby the consumption of certain medications prescribed is determining for the allocation of patients to pharmaceutical cost groups (PCG). Additionally a classification into diagnosis cost groups (DCG) according to stationary diagnoses was conducted. RESULTS: Within the scope of the enrollment models the formation of matched pairs following the PCG/DCG procedure represents an appropriate study design for the creation of a control group. In the first year of enrollment the insured of the interventional and those of the control group show a comparable morbidity. When applying 9 matching criteria a control insured person can be found for 87% of the enrolled individuals. DISCUSSION/CONCLUSIONS: There are various and complex possibilities to define morbidity. Variable parameters within the presented matched pairs design are the number of used matching criteria as well as minimum drug consumption limit relevant for the classification in PCGs. Alternative models are possible for morbidity definition considering, apart from the stationary diagnosis, also the ambulant diagnosis. When taking into account a higher number of morbidity criteria, the matched pairs design is confronted with dimensionality issues. The propensity score matching is discussed as approach to solve this problem.

[Drug interactions]. / Arzneimittelinteraktionen.

Drug-drug interactions can be used to enhance effectiveness but they are also a significant cause of adverse drug reactions. Alterations in liberation, absorption, distribution, metabolism, and excretion may all affect the pharmacokinetics of a drug. Cytochrome P450 enzymes and drug transporters like ABC-transporters determine the clearance of many drugs leading to alterations in therapeutic effect. In contrast pharmacodynamic drug interactions will alter drug effects in the absence of concentration changes of the co-administered drug. Alterations of a drug effect may require changes in dose to maintain the therapeutic effect.

[Patient recruitment in clinical studies]. / Die richtige Rekrutierung von Studienteilnehmern.

Patient recruitment in clinical studies is an essential step early in a drug trial. The quality of this process determines the safety of the trial and may modulate the validity of the resulting scientific information. While there are good reasons to recruit participants as quickly as possible to accelerate drug development and promote new treatment options, it is even more important to safeguard health and well-being of the participant. Therefore all steps of recruitment from patient identification and patient availability to patient information and enrolment have to be tailored accordingly. This paper describes the numerous challenges in this task, pitfalls and risks that may jeopardize reliable and effective recruitment, and strategies to improve this important process.

Three-dimensional in vitro cell biology models of ovarian and endometrial cancer.

OBJECTIVES: This study aims to establish three-dimensional (3D) cell culture models of human ovarian and endometrial cancers and to compare biological and morphological characteristics of these models with those of two-dimensional (2D) models of the same cell lines and the primary tumours. METHODS: 3D models of ovarian and endometrial cancer cell cultures were established using a Rotary Cell Culture System. Immunohistochemical profiling and differential proteomics were used to characterize biological characteristics of multicellular spheroids (MCS) formed from these cultures. These were compared to characteristics of the same cells established in 2D and of the primary tumours from which the cell lines were derived. RESULTS: MCSs from 3D cell cultures appeared histologically similar to the primary tumours. Immunohistochemical profiling of multiple markers, including CA125, BCL2 and p53, showed that patterns of protein expression in MCSs resemble those of the primary tumours. Proteomic profiling identified several differentially expressed protein markers between 2D and 3D cultures. These included prohibitin, which was down-regulated in 3D cultures suggesting cells proliferate less compared to 2D cultures; and VDAC1 and annexin 4, which were up-regulated in 3D cultures suggesting greater levels of apoptosis in 3D compared to 2D models. CONCLUSION: Establishing 3D models of cancer cell lines is likely to be of value for studying the molecular and biological mechanisms of ovarian/endometrial tumour progression and for testing novel molecular targets for cancer therapy.

[The importance of dental-based treatment shown on the case report of a pontine abscess caused by Streptococcus viridans]. / Die Bedeutung der zahnbezogenen Focussanierung am Fallbeispiel eines pontinen Abszesses durch Streptokokken der Viridans Gruppe.

BACKGROUND: The treatment of infectious oral lesions is an important prophylactic procedure preceding immunsuppressive therapy. The case reported underlines the importance of this treatment by showing severe complications of an infective dental focus in an immunocompetent patient. CASE REPORT: A 65 year old patient was referred to hospital due to neurological disorders including hypaesthesia, movement deficits, nausea and falls. Because of progressive aggravation with hemiplegia a craniotomy and biopsy of a suspicious area in the pons was performed. A brain stem abscess caused by Streptococcus viridans was diagnosed. Brain stem abscesses are very rare events who contribute to only about 0.6%-6% of all intracranial abscesses. The intraoral inspection revealed a periodontally diseased and carious affected dentition with many missing teeth. Other foci were ruled out. Because of persistency of the symptoms another operation with abscess drainage was performed. Afterwards the clinical symptoms improved but hemiplegia was still present. CONCLUSIONS: Even minor dental procedures as well as existence of a carious or periodontal disease may cause bacteremia with severe septical implications. Patients at risk (e.g. dieases of the heart valves or diabetes) should always treated with an antibiotic prophylaxis before treatment according to the guidelines of the DGZMK. All oro-pharyngeal infectious foci have to be treated sufficiently to prevent sceptical complications. Even more important is the prophylactic treatment preceding chemo- or radiation therapy.

Increased frequency of migraine in narcoleptic patients.

We explored the relationship between narcolepsy and different types of headaches. We interviewed 68 patients with idiopathic narcolepsy for the presence of headache symptoms based on the criteria of the International Headache Society (IHS). Eighty-one percent of the patients reported headaches that warranted an IHS headache diagnosis. Fifty-four percent of the patients (64% women, 35% men) had migraine with all IHS criteria fulfilled.

Electrophysiological brain stem investigations in idiopathic narcolepsy.

Narcolepsy is associated with various rapid eye movement (REM) sleep abnormalities. Distinct brain stem areas seem to play a prominent role in REM sleep regulation. Recent magnetic resonance imaging (MRI) studies have led to conflicting findings concerning the presence of structural brain stem lesions in patients with idiopathic narcoleptic syndrome. However, multimodal electrophysiological brain stem investigations may reveal functional brain stem abnormalities even in the absence of MRI abnormality. Therefore we investigated brain stem function in 12 idiopathic narcoleptic patients by systematically studying tegmental brain stem pathways. All of the patients met the diagnostic criteria of the International Classification of Sleep Disorders, with typical changes in polysomnography and the multiple sleep latency test. Electrophysiological investigations comprised masseter reflex, blink reflex, masseter inhibitory reflex, early auditory evoked potentials and electrooculography with vestibular testing. In no patient were electrophysiological brain stem abnormalities observed. Our findings do not support the existence of a relevant brain stem lesion in narcoleptic patients with normal neurological status.

[Percutaneous transluminal angioplasty of the deep femoral artery. Retrospective evaluation of early technical and clinical results in 196 cases of catheterization]. / Perkutane transluminale Angioplastie der Arteria profunda femoris. Retrospektive Auswertung der technischen und klinischen Frühergebnisse von 196 Katheterbehandlungen.

AIM: Stenosis of the deep femoral artery with simultaneous occlusion of the superficial femoral artery usually is considered to be a classical indication for vascular surgery. Angioplastic therapy of this vessel is rarely reported. Retrospective analysis of the technical and clinical results following catheter treatment of the deep femoral artery was performed to demonstrate the possibilities of this less invasive method. MATERIAL AND METHOD: 196 angioplasties in 174 patients were performed. 77 patients (39%) suffered from stage II disease according to Fontaine classification (grade I category 2/3 [Rutherford]), 36 (18%) from stage III (grade II category 4) and 75 (38%) from stage IV (grade III category 5). RESULTS: Catheter treatment was successfully performed in 77% (151/196) of the cases. Clinical improvement was seen following 61% (96/196) of the treatments. The complication rate was 3.4% (7/196: thrombosis of the CFA, ascending occlusion of the SFA, occlusion/spasm of the arteria circumflexa femoris lateralis, pulmonary embolism). CONCLUSION: Catheter treatment is a minimal invasive, cost-effective alternative to surgical reconstruction of the deep femoral artery.

[MRI and oncoscintigraphy with 99m-Tc-MIBI in the follow up of thyroid cancer]. / KST und Onkoszintigraphie mit 99mTc-MIBI in der Nachsorge des Schilddrüsenkarzinoms.

Magnetic resonance imaging (MRI) and 99mTc-MIBI oncoscintigraphy are new procedures for the detection of recurrent differentiated thyroid cancer. We evaluated the utility of both techniques compared to ultrasonography, radioiodine scanning, and measurement of serum thyroglobulin in patients with (n = 21) or without suspicion (n = 34) of tumor relapse. Although MRI was most effective in detecting local recurrencies (sensitivity: 100%), additional diagnostic information was only obtained in patients with mediastinal lesions. On the other hand, oncoscintigraphy was less sensitive (67%) but highly specific in differentiating reactive lymph node enlargement from metastatic disease (specificity: 93.5%). Oncoscintigraphy may be used instead of radioiodine scanning in patients with doubtful lymph node findings and spare them withdrawal of TSH-suppressive hormone medication. Routine estimation of serum thyroglobulin proved to be highly efficient in screening for tumor relapse using a cut-off level of 3 ng/ml (accuracy: 100%).

[An incidental finding of a progressive diaphyseal dysplasia (Camurati-Engelmann syndrome)]. / Zufallsbefund einer progressiven diaphysären Dysplasie (Camurati-Engelmann-Syndrom).

In a 35 year-old female diaphyseal hyperostosis of femur and tibia indicative of a Camurati-Engelmann syndrome (progressive diaphyseal dysplasia) were discovered during routine phlebography. This rare disorder belongs to the group of osteochondrodysplasias and affects primarily the diaphyses of long bones. Sporadic as well as familial cases have been observed. Although the cause and pathogenetic mechanism of the disease are unknown, an autosomal dominant inheritance is being discussed. Diagnosis was based on radiological findings, which are presented along with the scintigraphic appearance of the disease.

[Color-coded duplex ultrasonography in the diagnosis of renal artery stenosis]. / Farbkodierte Duplexsonographie in der Diagnostik von Nierenarterienstenosen.

To diagnose possible renal artery stenosis in 120 patients (36 women, 84 men; mean age 57.3 [21-84] years) colour duplex sonography (CDS) of the renal arterial tree was performed before 53 intraarterial angiographies and 67 central venous digital subtraction angiographies. The criterion of stenosis was a maximal flow velocity of > 180 cm/s in the colour duplex sonogram and a diameter reduction of > 50% in the angiogram. CDS demonstrated the renal artery bed in 209 of 247 renal arteries (85%). 84 of the 209 had regional maximal velocities of > 180 cm/s. The sensitivity and specificity of CDS when comparing it with both angiographic methods (in 185 cases that could be evaluated, in 74 of them with abnormal results) were 91 and 88.2%, respectively. Comparing CDS results with those by intraarterial angiography alone (88 cases, with 51 abnormal findings), sensitivity and specificity were 92.1 and 91.8%, respectively. These results demonstrate that CDS can reliably demonstrate flow obstructions in the renal arterial tree and can thus be recommended for the diagnosis of renovascular hypertension.

[Determination of the length of the occlusion in extremity arteries--color duplex ultrasound versus angiography]. / Bestimmung der Verschlusslänge in Extremitätenarterien--Farbduplexsonographie versus Angiographie.

In the management of patients with peripheral arterial occlusive disease the length and location of an arterial occlusion has an impact on the choice of the method of arterial reconstruction, i.e. percutaneous transluminal angioplasty or vascular surgery. The aim of this study was to determine the accuracy of colour-coded Doppler sonography (CDS) compared to conventional contrast arteriography in detecting the length and localisation of an occlusion in peripheral arteries. 100 legs of 94 patients (27 women, 44 to 82 years of age [mean 60.9 years] and 67 men, 21 to 78 years of age [mean 61.3 years]) with clinically suspected artery occlusion were examined prospectively with CDS before angiography and angioplasty. The exact localisation was correctly diagnosed by CDS in 95% with a high correlation (r = 0.95) of occlusion length between both methods. The sensitivity in detecting occlusions was 98% (positive predictive value 98%). It is concluded that colour-coded Doppler sonography can diagnose the length and location of an occlusion in peripheral arteries accurately and therefore can be used as a noninvasive method to select patients for further therapy management.

[Progress in arterial reconstruction of the upper and lower leg--percutaneous transluminal procedures]. / Fortschritte arterieller Rekonstruktion an Ober- und Unterschenkel--Perkutane transluminale Verfahren.

Conventional PTA represents the state of the art method for treating arterial occlusive disease of the leg arteries. Rotational angioplasty is an improvement over conventional PTA in treating long proximal occlusions of the SFA. It can also be used as a second treatment in cases that were primarily unsuccessful with PTA, with an initial success of 59%. Stent implantation is mainly indicated in limb-threatening ischemia. It also permits successful management of an aneurysm as a late and rare complication correlated to PTA. Atherectomy produces better initial success in eccentric stenotic lesions than PTA. It also permits the successful management of obstructive intimal flaps after angioplasty. The new techniques only improve on PTA, if they are used in the differential therapeutic strategy mentioned above.

[Osteonecrosis of the ossa sesamoidea hallucis--its pathology, diagnosis and differential diagnosis]. / Die Osteonekrose der Ossa sesamoidea hallucis--Pathologie, Diagnose und Differentialdiagnose.

Basing on case reports, the embryology and anatomy of the great toe sesamoid bones are described. Pathogenesis of the osteonecrosis of these bones is explained, and the role of radiology in diagnosis and as an important aid in differential diagnosis is pointed out.

Metabolism and actions of 2-deoxy-2-fluoro-D-galactose in vivo.

The synthetic D-galactose analog 2-deoxy-2-fluoro-D-galactose (dGalF) offers unique advantages for studies of the D-galactose pathway by non-invasive techniques using 19F-NMR spectroscopy or positron emission from the 18F-labeled compound. The metabolism of 2-deoxy-2-fluoro-D-galactose was studied in rodents using the unlabeled, the 18F-labeled, and the 14C-labeled D-galactose analog. Analyses for the metabolites of 2-deoxy-2-fluoro-D-galactose were performed by HPLC, enzymatic methods, and 19F-NMR spectroscopy in vivo and in vitro. The metabolism of 2-deoxy-2-fluoro-D-galactose was most active in the liver which took up the major part of the administered dose of the 14C-labeled D-galactose analog, but renal excretion was also pronounced. This was confirmed by in vivo scanning of the rat using the 18F-labeled sugar (1.5 microCi/g; 25 nmol/g) and examination by positron-emission tomography and gamma camera. The dose dependence of the levels of the hepatic metabolites of 2-deoxy-2-fluoro-D-galactose was investigated for doses between 25 nmol/g body mass and 1 mumols/g body mass. After 1 h, the major part of the acid-soluble uracil nucleotides consisted of UDP-2-deoxy-2-fluoro-D-hexoses when the dose was at least 0.1 mumols/g. With higher doses, 2-deoxy-2-fluoro-D-galactose 1-phosphate became the predominant initial metabolite. After a dose of 1 mumols/g 2-deoxy-2-fluoro-D-galactose 1-phosphate accumulated rapidly (5.3 +/- 0.4 mumols/g liver after 30 min) followed by the formation of UDP-2-deoxy-2-fluoro-D-galactose and UDP-2-deoxy-2-fluoro-D-glucose (0.7 +/- 0.1 mumols/g and 1.8 +/- 0.1 mumols/g, respectively, after 5 h). The diversion of uridylate, due to the accumulation of UDP-2-deoxy-2-fluoro-D-hexoses, was associated with a rapid depletion of hepatic UTP, UDP-glucose, and UDP-galactose. The UTP content was decreased to 11 +/- 6% of normal within 15 min after administration of 2-deoxy-2-fluoro-D-galactose at a dose of 1 mumols/g. The UTP-depleting action was minimal, however, at a dose of 25 nmols/g or less, indicating that interference in uridylate metabolism would be negligible at the doses required for positron-emission tomography of the liver using the 18F-labeled compound. At higher doses, the UTP deficiency induced by 2-deoxy-2-fluoro-D-galactose could be useful in the chemotherapy of D-galactose-metabolizing tumors such as hepatocellular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo metabolism and UTP-depleting action of 2-deoxy-2-fluoro-D-galactose.

The metabolism of 2-deoxy-2-fluoro-D-galactose (dGalF) was studied in rodents using HPLC, enzymatic methods, and 19F-NMR spectroscopy in vivo and in vitro. The liver took up the major part of the administered dose of the 14C-labeled D-galactose analog. This was confirmed in vivo by use of the 18F-labeled sugar (1.5 mCi/kg; 25 mumol/kg) and examination by positron emission tomography. After a dose of 1 mmol/kg, dGalF-1-phosphate accumulated rapidly (5.3 +/- 0.4 mmol/kg after 30 min), followed by formation of UDP-dGalF and UDP-2-deoxy-2-fluoro-D-glucose (0.7 +/- 0.1 and 1.8 +/- 0.1 mmol/kg, respectively, after 5 hr). Good quantitative agreement was obtained between the measurements by HPLC and enzymatic analyses and by 19F-NMR. The noninvasive in vivo 19F-NMR technique is particularly advantageous, since it allows the simultaneous analysis of all dGalF metabolites. The diversion of uridylate, due to the accumulation of UDP-2-deoxy-2-fluoro-D-hexoses, was associated with a rapid depletion of hepatic UTP, UDP-glucose, and UDP-galactose. The UTP content was decreased to 11 +/- 6% of normal within 15 min after administration of dGalF at a dose of 1 mmol/kg. The UTP-depleting action was minimal, however, at a dose of 25 mumol/kg or less, indicating that interference in uridylate metabolism will be negligible at the doses required for positron emission tomography of the liver using the 18F-labeled compound. At higher doses the UTP deficiency induced by dGalF may be useful in the chemotherapy of D-galactose-metabolizing tumors such as hepatocellular carcinoma. At moderate doses of dGalF, 19F-NMR spectroscopy in vivo or in vitro could be used to pinpoint defects of the enzymes that cause galactosemia, i.e. of galactokinase, uridyltransferase, or 4-epimerase.

[Asymptomatic calcified aneurysm of the inferior pancreaticoduodenal artery--differential diagnostic considerations]. / Asymptomatisches verkalktes Aneurysma der Arteria pancreaticoduodenalis inferior--differentialdiagnostische Uberlegungen.

A calcified aneurysm of the inferior pancreaticoduodenal artery with simultaneous occlusion of the celiac axis but without any local symptoms is presented. In the description of the diagnostic procedure, the considerations relating to differential diagnosis against solitary circumferentially calcified masses in the right upper quadrant of the abdomen are discussed. As a result of increasingly sophisticated examination techniques, especially digital subtraction angiography, computed tomography and ultrasonography, these aneurysms, which were formerly thought to be rare, are now discovered surprisingly often. Knowledge of this vascular malformation and its differential diagnoses helps to avoid risky methods of examination.