Einsatz bakterieller Impfstoffe beim Menschen Ein Beitrag zur Verminderung der Anwendung von Antibiotika

Im “World Health Report 1998” der Weltgesundheitsorganisation (WHO) wird den Antibiotika ein bedeutender Anteil des Erfolges zugewiesen, der innerhalb der letzten 50 Jahre im Kampf gegen mikrobiell bedingte Infektionskrankheiten erzielt wurde. Gleichzeitig wird jedoch auf die enormen Probleme mit den sich ausbreitenden Resistenzen hingewiesen, wobei Mycobacterium tuberculosis und Streptokokkus pneumoniae in diesem Zusammenhang hervorgehoben werden. Nach Ansicht der WHO mu? den Impfstoffen künftig bei der Bek?mpfung von Infektionskrankheiten mehr Bedeutung zukommen [1]     

Regional right ventricular function and timing of contraction in healthy volunteers evaluated by strain‐encoded MRI

Purpose

To prospectively determine the feasibility and accuracy of strain‐encoded (SENC) magnetic resonance imaging (MRI) for the characterization of the right ventricular free wall (RVFW) strain and timing of contraction at 3.0 Tesla (3T) MRI.

Materials and Methods

In 12 healthy volunteers the RVFW was divided into three segments (anterior, lateral, and inferior) in each of three short‐axis (SA) slices (apical, mid, and basal) and into three segments (apical, mid, and basal) in a four‐chamber view. The study was repeated on a different day and interobserver and interstudy agreements were evaluated.

Results

Maximal systolic longitudinal strain values were highest at the apex and base, with a pronounced decrease in the medial segments (apex: –19.1% ± 1.4; mid: –17.4% ± 2; base: –19.4% ± 2.4, P < 0.001), and maximal systolic circumferential strain showed the highest values at the apex (apex: –18.1% ± 1.7; mid: –17.6% ± 1.2; base: –16.6% ± 0.9, P < 0.001). Peak systolic longitudinal and circumferential shortening occurred earliest at the apex compared to the mid‐ventricle and base. Excellent interobserver and interstudy correlation and agreement were observed.

Conclusion

The use of SENC MRI for the assessment of normal RV contraction pattern is feasible and accurate in 3T MRI. J. Magn. Reson. Imaging 2008;28:1379–1385. © 2008 Wiley‐Liss, Inc.     

Oncological outcome and patient satisfaction with skin-sparing mastectomy and immediate breast reconstruction: a prospective observational study

Background  

The management of early breast cancer (BC) with skin-sparing mastectomy (SSM) and immediate breast reconstruction (IBR) is not based on level-1 evidence. In this study, the oncological outcome, post-operative morbidity and patients' satisfaction with SSM and IBR using the latissimus dorsi (LD) myocutaneous flap and/or breast prosthesis is evaluated.     

Phase I trial of the positron-emitting Arg-Gly-Asp (RGD) peptide radioligand 18F-AH111585 in breast cancer patients.

The integrin alpha v beta3 receptor is upregulated on tumor cells and endothelium and plays important roles in angiogenesis and metastasis. Arg-Gly-Asp (RGD) peptide ligands have high affinity for these integrins and can be radiolabeled for PET imaging of angiogenesis or tumor development. We have assessed the safety, stability, and tumor distribution kinetics of a novel radiolabeled RGD-based integrin peptide-polymer conjugate, 18F-AH111585, and its feasibility to detect tumors in metastatic breast cancer patients using PET. METHODS: The biodistribution of 18F-AH111585 was assessed in 18 tumor lesions from 7 patients with metastatic breast cancer by PET, and the PET data were compared with CT results. The metabolic stability of 18F-AH111585 was assessed by chromatography of plasma samples. Regions of interest (ROIs) defined over tumor and normal tissues of the PET images were used to determine the kinetics of radioligand binding in tissues. RESULTS: The radiopharmaceutical and PET procedures were well tolerated in all patients. All 18 tumors detected by CT were visible on the 18F-AH111585 PET images, either as distinct increases in uptake compared with the surrounding normal tissue or, in the case of liver metastases, as regions of deficit uptake because of the high background activity in normal liver tissue. 18F-AH111585 was either homogeneously distributed in the tumors or appeared within the tumor rim, consistent with the pattern of viable peripheral tumor and central necrosis often seen in association with angiogenesis. Increased uptake compared with background (P = 0.002) was demonstrated in metastases in lung, pleura, bone, lymph node, and primary tumor. CONCLUSION: 18F-AH111585 designed to bind the alpha v beta3 integrin is safe, metabolically stable, and retained in tumor tissues and detects breast cancer lesions by PET in most anatomic sites.     

Tauroursodeoxycholic acid and secondary damage after spinal cord injury in rats.

Greater clinical understanding of the pivotal role of apoptosis in spinal cord injury (SCI) has led to new and innovative apoptosis-based therapies for patients with an SCI. Tauroursodeoxycholic acid (TUDCA) is a biliary acid with antiapoptotic properties. To our knowledge, this is the first study in the English language to evaluate the therapeutic efficacy of TUDCA in an experimental model of SCI. Thirty rats were randomized into three groups (sham-operated, trauma only, and trauma plus TUDCA treatment) of 10 each. In groups 2 and 3, spinal cord trauma was produced at the T8-T10 level via the Allen weight drop technique. Rats in group 3 were treated with TUDCA (200 mg/kg intraperitoneal) 1 min after trauma. The rats were killed either 24 h or 5 days after injury. The neuroprotective effect of TUDCA on injured spinal cord tissue and the effects of that agent on the recovery of hind-limb function were assessed. The efficacy of treatment was evaluated with histopathologic examination and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) analysis. Histopathologic characteristics were analyzed by comparison of hematoxylin-and-eosin stained specimens. Neurologic evaluations were performed 24 h, 3 days, and 5 days after trauma. Hind-limb function was assessed with the inclined plane technique of Rivlin and Tator and the modified version of Tarlov's grading scale. Twenty-four hours after injury, there was a significantly higher number of apoptotic cells in the lesioned spinal cord group than in the sham-operated control group. Treatment of the rats with TUDCA significantly reduced the number of apoptotic cells (4.52+/-0.30 vs. 2.31+/-0.24 in group 2) and the degree of tissue injury. Histopathologic examination showed that group 3 rats had better spinal cord architecture compared with group 2 rats. Five days after injury, the mean inclined plane angles in groups 1, 2, and 3 were 65.50 degrees +/- 2.09, 42.00 degrees +/- 2.74, and 53.50 degrees +/- 1.36. Motor grading of the rats revealed a similar trend. These differences were statistically significant (p<0.05). The mechanism of neuroprotection in the treated rats, although not yet elucidated, may be related to the marked antiapoptotic properties of TUDCA. A therapeutic strategy using TUDCA may eventually lead to effective treatment of SCI without toxic effects in humans.     

Atrial Arrhythmias in Long-QT Syndrome under Daily Life Conditions: A Nested Case Control Study

Background: The long-QT syndromes (LQTS) are inherited electrical cardiomyopathies characterized by prolonged ventricular repolarization and ventricular arrhythmias. Several genetic reports have associated defects in LQTS-causing genes with atrial fibrillation (AF). We therefore studied whether atrial arrhythmias occur in patients with LQTS under daily-life conditions.
Methods: We systematically assessed atrial arrhythmias in LQTS patients and matched controls using implanted defibrillators or pacemakers as monitors of atrial rhythm in a nested case-control study. Twenty-one LQTS patients (3 male; 39 ± 18 years old; 18 on β blocker, ICD therapy duration 6.3 ± 2.7 years; 4 LQT1, 6 LQT2, 2 LQT3) were matched to 21 control subjects (13 male; 50 ± 19 years old; 3 on β blocker; pacemaker therapy duration 8.5 ± 5.5 years; 19 higher-degree AV block, 2 others). LQTS patients were identified by a systematic search of the LQTS patient databases in Münster and Munich.
Results: One-third (7 of 21) of the LQTS patients developed self-terminating atrial arrhythmias (atrial cycle lengths <250 ms). Only one control patient developed a single episode of postoperative AF (P < 0.05 vs LQTS).
Conclusions: LQTS patients at high risk for ventricular arrhythmias may develop short-lasting atrial arrhythmias under daily-life conditions, suggesting that prolonged atrial repolarization may contribute to the initiation of AF.     

Macrocystic lymphatic lymphangioma (cystic lymphangioma) of the upper extremity: A case report

We report on a case of macrocystic lymphatic malformation of the forearm. A male infant, without any medical history, was followed up in our department since the age of 7 months because of a subcutaneous, soft, painless mass of the left forearm. Ultrasonography and the magnetic reasonance imaging (MRI) were evocative of a macrocystic lymphatic malformation. Five sessions of sclerotherapy led to the reduction of the size of the mass but another axillary tumor appeared afterwards. A surgical excision, unfortunately incomplete, was performed rapidly followed by a recurrence of the macrocystic lymphatic malformation. Macrocystic lymphatic malformations are localized in the neck in 75% and axilla in 20% of the cases. Involvement of the upper extremity and particularly the forearm is very rare. MRI is useful for the diagnosis and the definition of tumor limits. The treatment is usually challenging because of their location and rough delimitation.     

Pharmacokinetics of ceftazidime in patients with liver cirrhosis and ascites.

The pharmacokinetics of ceftazidime were studied in 18 male individuals, including six healthy volunteers and 12 patients with liver cirrhosis and ascites. Each participant received 1 g of ceftazidime as a single intravenous bolus injection. The elimination half-life was longer in cirrhotic than in control patients (5.40 +/- 1.02 h) vs. (1.98 +/- 0.24 h), P less than 0.01; probably due to slow return from the ascitic compartment. Nevertheless, total body clearance did not differ significantly between the two groups (81.4 +/- 30.3 ml/h/kg vs. 83.6 +/- 24.9 ml/h/kg). Dose reduction is not necessary when treating systemic infection in cirrhotics. Ceftazidime attained a concentration of 1 microgram/ml in the ascitic fluid in most patients 15 to 30 min after the injection, and maintained this level, which is higher than the MIC90 of Enterobacteriaceae, for 24 h. An intravenous bolus injection of 1 g ceftazidime every 24 h is sufficient to treat patients with spontaneous bacterial peritonitis caused by a susceptible organism other than Pseudomonas aeruginosa.     

Dynamic cavernosography in the evaluation of impotence

Dynamic carvernosography before and after papaverine injection into the corpus cavernosum of 6 sexually normal volunteers and 44 impotent patients was performed with digital subtracting angiography technique. The average infusion rates in 26 patients with venous leakage were 325.5 ml/min for induction of erection and 161 ml/min for maintenance. The results for the remaining 18 impotent patients without venous leakage were 128.8 ml/min for induction and 56.9 ml/min for maintenance. Similarly, the control group had average infusion rates of 128.3 ml/min for induction and 58.3 ml/min for maintenance. After papaverine injection the average infusion rates decreased to 131 ml/min (induction) and 59 ml/min (maintenance) in patients with venous leakage, 38.4 ml/min and 14.6 ml/min in the impotent patients without venous leakage and 35 ml/min and 14.1 ml/min in the control group, respectively. It was also noticed that in the control group filling of the superficial and deep veins may occur during the flaccid phase which disappeared with induced erection. Therefore we suggest intracavernous papaverine injection with dynamic cavernosography. The digital subtracting technique eliminates unnecessary images, providing a more accurate diagnosis of venius incompetence.     

Changes in soft tissue profile after mandibular setback surgery in Class III subjects

The aim of this study was to investigate changes in hard and soft tissue profile after mandibular setback surgery. Lateral cephalograms of 25 Class III subjects were assessed before and 1.5 ± 0.4 years after mandibular setback surgery. Paired t test, Pearson correlation test and linear regression analysis were used to evaluate the changes in soft tissue profile. Significant changes were found in skeletal (SNB ?3.6 ± 0.9°, ANB 3.7 ± 1.0°, overjet 5.0 ± 1.2 and overbite 2.5 ± 1.1 mm, P < 0.001), soft tissue (facial convexity 5.9 ± 1.6°, P < 0.001; labiomental fold 0.6 ± 0.6 mm, P < 0.001; upper and lower lip protrusion 0.5 ± 0.8 mm, P < 0.01; ?3.3 ± 1.2 mm, P < 0.001), and upper and lower lip lengths (0.9 ± 1.2 mm, P < 0.01; ?1.8 ± 2.1 mm, P < 0.001). Correlations were found between facial convexity and SNB and ANB angles and between upper lip length and SNB and ANB angles. The change in lower lip length was correlated with SNB, ANB, overjet and overbite. Lower lip retrusion was correlated with overjet and a significant correlation was found between the retrusion of lower incisor and lower lip. Mandibular setback surgery was effective in producing an orthognathic profile in adult Class III subjects with mandibular prognathism.