High prevalence of abdominal aortic aneurysm in older men with cerebrovascular disease: Evaluation of a local screening program.

Introduction: Patients with cerebrovascular disease may suffer from other vascular morbidities, such as abdominal aortic aneurysm (AAA). Previously, a high prevalence of AAA has been demonstrated in men 60 years of age and older who have experienced TIA or stroke. This report evaluates the results of a decade's operation of a local screening program for AAA in this selected neurologic population. Methods: Men aged ≥60 years and admitted to the neurology ward of a community-based hospital in the Netherlands from 2006 to 2017 with a diagnosis of TIA or stroke were selected for screening. The diameter of the abdominal aorta was assessed by abdominal ultrasonography. Patients with detected AAA were referred for evaluation by a vascular surgeon. Results: AAA was detected in 72 of 1,035 screened patients (6.9%). AAAs with a diameter of 3.0-3.9 cm accounted for 61.1% of the total aneurysms found; AAAs with a diameter of 4.0-5.4 cm accounted for 20.8% of the total; and large aneurysms with a diameter of ≥5.5 cm accounted for 18.1% of all aneurysms discovered. A total of 18 patients (1.7%) underwent elective aneurysm repair. Discussion: The detection rate of AAA in older men with cerebrovascular disease was roughly 5-fold the detection rate in known European screening programs in older men from the general population. The proportion of large AAAs (≥5.5 cm) was also substantially higher. These findings reveal a previously unknown co-morbidity in patients with cerebrovascular disease and may be helpful for cardiovascular management of this large group of neurologic patients. Current and future AAA screening programs may also benefit from this knowledge.

[Paget's disease of bone-a current review of clinical aspects, diagnostics and treatment]. / Morbus Paget des Knochens ­ eine aktuelle Übersicht zu Klinik, Diagnostik und Therapie.

Paget's disease is a monostotic or polyostotic progressive skeletal disease with a genetic predisposition. The affected bone areas show osseous swelling and often grotesque deformation, chronic pain and fractures. Many cases are asymptomatic for a long time resulting in a late diagnosis. The pathogenesis is still unknown. In addition to a genetic predisposition, viral factors are also discussed. Laboratory tests and imaging are used for diagnosis. The effective principle of medicinal bisphosphonate treatment is to inhibit osteoclastic bone resorption and should be initiated early to prevent secondary complications. This article presents the current knowledge about this rare osteological disease.

Maternal high-fat diet during lactation reprograms the dopaminergic circuitry in mice.

The maternal perinatal environment modulates brain formation, and altered maternal nutrition has been linked to the development of metabolic and psychiatric disorders in the offspring. Here, we showed that maternal high-fat diet (HFD) feeding during lactation in mice elicits long-lasting changes in gene expression in the offspring's dopaminergic circuitry. This translated into silencing of dopaminergic midbrain neurons, reduced connectivity to their downstream targets, and reduced stimulus-evoked dopamine (DA) release in the striatum. Despite the attenuated activity of DA midbrain neurons, offspring from mothers exposed to HFD feeding exhibited a sexually dimorphic expression of DA-related phenotypes, i.e., hyperlocomotion in males and increased intake of palatable food and sucrose in females. These phenotypes arose from concomitantly increased spontaneous activity of D1 medium spiny neurons (MSNs) and profoundly decreased D2 MSN projections. Overall, we have unraveled a fundamental restructuring of dopaminergic circuitries upon time-restricted altered maternal nutrition to induce persistent behavioral changes in the offspring.

[Multimodal rheumatologic complex treatment of rheumatoid arthritis-a monocentric retrospective analysis]. / Multimodale rheumatologische Komplexbehandlung bei rheumatoider Arthritis ­ eine monozentrische Retrospektivanalyse.

BACKGROUND: Multimodal rheumatologic complex treatment (MRCT, operation and procedures classification system, OPS code 8­983) is a specific concept of acute inpatient care (DRG I97Z) for treatment of patients with rheumatic diseases, degenerative diseases and/or chronic pain syndromes suffering from exacerbated pain and functional impairment. OBJECTIVE: A monocentric retrospective analysis of the effects of MRCT on pain and functional status in patients with rheumatoid arthritis (RA) was conducted. METHODS: A total of 103 treatment episodes in 75 patients with proven RA who received MRCT between 2014 and 2017 were included in the analysis. The changes in pain intensity were evaluated using a numerical rating scale (NRS), the functional limitations as assessed by the Hanover function questionnaire (FFbH) and the health assessment questionnaire (HAQ) and the disease activity (disease activity score of 28 joints, DAS28) before and after MRCT episodes. In addition, the patient characteristics and the course of the disease were documented and a univariate analysis of the influence of these factors on the parameters activity and function was performed. RESULTS: In patients with RA, the MRCT resulted in a significant amelioration of pain (p < 0.0001), a significant improvement of functional capacity (FFbH p = 0.0013, HAQ p = 0.1396) and a significant reduction of disease activity (DAS28 p < 0.0001). Different aspects of the disease and its previous course (e. g. disease duration, type and number of previous anti-rheumatic drugs, current medication) did not have a significant effect on the response. CONCLUSION: This retrospective monocentric analysis proved the efficacy of MRCT with respect to the inpatient treatment period in a large cohort of RA patients. This treatment concept not only improved pain and function (FFbH) but also significantly reduced the disease activity.

A Pulsatile Mass in the Right Buttock.

Gluteal artery pseudoaneurysms are a rare cause of buttock pain, with few cases reported in the recent literature. Although small pseudoaneurysms are usually asymptomatic, larger can be painful and require treatment. Most of these cases are pseudoaneurysms resulting from local trauma. We report in this case a patient with a gluteal artery pseudoaneurysm. The pseudoaneurysm was successfully thrombosed using ultrasound-guided thrombin injection. This article reviews the literature, discusses the imaging diagnostics and the treatment of gluteal artery aneurysms.

Mechanical stress enhances CD9 expression in cultured podocytes.

Elevated glomerular pressure represents a high risk for the development of severe kidney diseases and causes an increase in mechanical load to podocytes. In this study, we investigated whether mechanical stress alters gene expression in cultured podocytes using gene arrays. We found that tetraspanin CD9 is significantly upregulated in cultured podocytes after mechanical stress. The differential expression of CD9 was confirmed by RT-PCR and Western blotting under stretched and unstretched conditions. Furthermore, mechanical stress resulted in a relocalization of CD9. To get an insight into the functional role of CD9, podocytes were transfected with pEGFP-CD9. The expression of CD9 induced the formation of substratum-attached thin arborized protrusions. Ca(2+) depletion revealed that podocytes overexpressing CD9 possess altered adhesive properties in contrast to the control transfected cells. Finally, elevated CD9 expression increased migration of podocytes in a wound assay. In summary, our results suggest that upregulation of CD9 may play an important role in podocyte morphology, adhesion, and migration.

Adhesion of food-borne bacteria to stainless steel is reduced by food conditioning films.

AIMS: Preconditioning of stainless steel with aqueous cod muscle extract significantly impedes subsequent bacterial adhesion most likely due to repelling effects of fish tropomyosin. The purpose of this study was to determine if other food conditioning films decrease or enhance bacterial adhesion to stainless steel. METHODS AND RESULTS: Attachment of Pseudomonas fluorescens AH2 to stainless steel coated with water-soluble coatings of animal origin was significantly reduced as compared with noncoated stainless steel or stainless steel coated with laboratory substrate or extracts of plant origin. Coating with animal extracts also decreases adhesion of other food-relevant bacteria. The manipulation of adhesion was not attributable to growth inhibitory effects. Chemical analysis revealed that the stainless steels were covered by homogenous layers of adsorbed proteins. The presence of tropomyocin was indicated by appearance of proteins with similar molecular weight based in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, in several extracts that reduced adhesion but also extracts not containing this protein reduced bacterial adhesion, indicating that several molecular species may be involved in the phenomenon. CONCLUSIONS: It is a common perception that food materials facilitate bacterial adhesion to surfaces; however, this study demonstrates that aqueous coatings of food origin may actually reduce bacterial adhesion. SIGNIFICANCE AND IMPACT OF THE STUDY: Compounds from food extracts may potentially be used as nontoxic coatings to reduce bacterial attachment to inert surfaces.

Anti-adhesive properties of fish tropomyosins.

AIMS: We have recently found that preconditioning of stainless steel surfaces with an aqueous fish muscle extract can significantly impede bacterial adhesion. The purpose of this study was to identify and characterize the primary components associated with this bacteria-repelling effect. METHODS AND RESULTS: The anti-adhesive activity was assayed against Escherchia coli K-12, and bacterial adhesion was quantified by crystal violet staining and sonication methods. Proteolytic digestion, elution and fractionation experiments revealed that the anti-adhesive activity of the extract was linked to the formation of a proteinaceous conditioning film composed primarily of fish tropomyosins. These fibrous proteins formed a considerable anti-adhesive conditioning layer on and reduced bacterial adhesion to several different materials including polystyrene, vinyl plastic, stainless steel and glass. The protein adsorption profiles obtained from the various materials did not differ significantly, but elution was often incomplete making minor qualitative/quantitative differences indiscernible. CONCLUSIONS: The data highlights the significance of protein conditioning films on bacterial adhesion and emphasizes the importance of substratum's physiochemical properties and exposure time with regards to protein adsorption/elution efficiency and subsequent bacterial adhesion. SIGNIFICANCE AND IMPACT OF THE STUDY: Fish tropomyosin-coatings could potentially offer a nontoxic and relatively inexpensive measure of reducing bacterial colonization of inert surfaces.

[Tracheal agenesis. A rare cause of respiratory insufficiency in neonates]. / Trachealagenesie. Eine seltene Ursache der respiratorischen Insuffizienz des Neugeborenen.

Tracheal agenesis is a very rare congenital anomaly that occurs isolated or in combination with other anomalies. It presents immediately after birth with an absolute respiratory insufficiency and lack of crying. The immediate precise anatomical classification of the anomaly is crucial in order to decide if surgical therapy is possible. This report describes a newborn boy with tracheal agenesis type II. The diagnosis was confirmed by spiral computed tomography and a selection of the pictures is presented. The treatment was discontinued due to a lack of therapeutical options. Based on this case report we discuss the special situation of this rare anomaly. Interesting information on tracheal agenesis was gathered, the differential diagnosis of respiratory insufficiency of the newborn is summarised and a modified algorithm of the current newborn resuscitation guidelines of the American Heart Association is presented.

Laparoscopic coagulation of the uterine blood supply in laparoscopic-assisted vaginal hysterectomy is associated with less blood loss.

BACKGROUND: Does laparoscopic coagulation of the uterine blood supply decrease blood loss compared with transvaginal ligature of the uterine vessels? METHODS: Intra- and postoperative data of 446 patients undergoing laparoscopic-assisted vaginal hysterectomy at the Department of Gynecology, University of Jena, between 1998 and 2001 were analysed. In 213 patients the uterine blood supply was transected laparoscopically at the origin of the uterine vessels (LAVH type II) and in 233 patients (LAVH type I) transvaginally. RESULTS: Patients in both groups were comparable with respect to median age, Quetelet index, and parity. The drop of hemoglobin between the preoperative day and postoperative day 3 was 0.8 mmol/l or 0.6 mmol/l for LAVH type I without or with BSO vs 0.3 mmol/l or 0.4 mmol/l for LAVH type II without or with BSO (p = 0.001), respectively. Median operative time was similar for both techniques: LAVH type I 136 min or with BSO 128 min vs LAVH type II 126 min or with BSO 131 min. The weight of the removed uteri was significantly lower in LAVH type I vs type II (220 vs 270 grams), but similar when LAVH was combined with BSO (160 vs 178 grams). The rate of intraoperative complications was 2.2% vs 0.9% between LAVH type I or II (n.s.), but 9% vs 3.3% for overall postoperative complications (p = 0.01). CONCLUSIONS: Laparoscopic coagulation of the uterine blood supply at the origin of uterine vessels is a safe technique which minimizes blood loss in LAVH. In patients with a low preoperative hemoglobin value this technique is indicated.

Vascular graft infection in aortoiliac and aortofemoral bypass surgery: clinical presentation, diagnostic strategies and results of surgical treatment.

OBJECTIVES: Evaluation of the prevalence, diagnostic procedures and clinical outcome of infections of aortoiliac and aortofemoral vascular grafts presented in our centre. DESIGN: Retrospective study. MATERIALS: All patients who underwent a surgical aortoiliac or aortofemoral revascularisation between 1991 and 2001. METHODS: Evaluation of several hospital databases. RESULTS: 32 cases of aortoiliac and aortofemoral vascular graft infection with varied clinical presentation were found. Enteral bleeding was the first clinical manifestation in 31% of the cases, inguinal swelling, wound, or fistula in 59% and fever or sepsis in 6.3%. In 3% the cause was unknown. The vast majority (84.5%) of the infections presented three or more months after surgery (late infections). In cases of enteral bleeding, endoscopy procedures only revealed the diagnosis in 55%. Diagnostic algorithms including an abdominal CT scan appeared to have a sensitivity of 94% for establishing an accurate diagnosis. Remarkably, no specific risk factors for graft infection could be demonstrated. Furthermore, a 30-day survival of 20% or less was observed in early graft infections, whereas late infections managed with extra-anatomical bypasses appeared to have a better survival rate of up to 70%. CONCLUSION: Endoscopy in cases of enteral bleeding and CT scanning overall were shown to be very useful for establishing the diagnosis. Clinical outcome and survival after treatment remain poor.

Resection of presacral ganglioneurofibroma by laparoscopy.

BACKGROUND: Tumors of the retrorectal space are rare. They comprise a heterogeneous group of benign or malignant tumors that cause similar symptoms due to their location in presacral space. If possible, complete surgery excision is the therapy of choice mainly through a sacral, abdominal-sacral, or a pure abdominal or perineal axis. CASE REPORT: A 15-year-old asymptomatic patient was diagnosed with a retrouterine tumor during her first gynecological examination. Magnetic resonance imaging of the pelvis showed a 10 x 8.5 x 7-cm encapsulated presacral tumor. Retrorectal ganglioneurofibroma was removed by laparoscopy with preservation of the sympathetic and parasympathetic nerves and the sacral roots of the ischiadic nerves. No sensory or motoric dysfunction of the legs, bladder, or rectum was observed postoperatively. CONCLUSION: This is the first case report of a complete endoscopic removal of large presacral ganglioneurofibroma in an asymptomatic woman.

Laparoscopic-assisted vaginal hysterectomy with lateral transsection of the uterine vessels.

BACKGROUND: Increased safety and diminished blood loss are achieved through laparoscopic-assisted vaginal hysterectomy by selective coagulation and transsection of the uterine vessels at their origin. METHODS: Three laparoscopic steps are performed: coagulation and transsection of the round ligament, of the uterine artery at its origin, and of the fallopian tube and ovarian ligament or (in BSO) the infundibulopelvic ligament. The uterine vessels are identified from the pararectal space and, following the internal liliac artery, and the ureter. Hysterectomy is completed transvaginally. RESULTS: Two hundred and sixty-seven patients underwent this procedure. Mean operation time was 121 min, and hemoglobin decreased to 0.6 g/dl by postoperative day 3. It took 8.4 min on average to identify and coagulate the uterine artery. CONCLUSIONS: Lateral transsection of the uterine vessels is safe and blood sparing and can be used in patients in whom blood loss must be minimized.

DNA microarray analysis of fim mutations in Escherichia coli.

Bacterial adhesion is often mediated by complex polymeric surface structures referred to as fimbriae. Type 1 fimbriae of Escherichia coli represent the archetypical and best characterised fimbrial system. These adhesive organelles mediate binding to D-mannose and are directly associated with virulence in the urinary tract. A typical type 1 fimbriated bacterium has up to 500 fimbriae on its surface, with each fimbria consisting of approximately 1000 individual subunits. This equates to approximately 8% of the total cellular protein and is potentially a significant resource drain for the cell. Here we have used DNA microarray analysis to examine the molecular events involved in response to fimbrial gene expression in E. coli K-12. Observed differential expression levels of the fim genes were in good agreement with our current knowledge of the stoichiometry of type 1 fimbriae. Changes in fim expression correlated directly with alterations in colony morphology. Deletion of the entire fim gene cluster resulted in the converse expression of another surface protein Antigen 43 (Ag43). Specific deletion of the fimH gene did not affect expression of other fim genes or Ag43, but did dramatically reduce the number of fimbriae expressed on the cell surface. The use of high-resolution oligonucleotide arrays for defining points of transcription initiation and termination is also demonstrated.

Novel Zn(2+)-chelating peptides selected from a fimbria-displayed random peptide library.

The display of peptide sequences on the surface of bacteria is a technology that offers exciting applications in biotechnology and medical research. Type 1 fimbriae are surface organelles of Escherichia coli which mediate D-mannose-sensitive binding to different host surfaces by virtue of the FimH adhesin. FimH is a component of the fimbrial organelle that can accommodate and display a diverse range of peptide sequences on the E. coli cell surface. In this study we have constructed a random peptide library in FimH. The library, consisting of approximately 40 million individual clones, was screened for peptide sequences that conferred on recombinant cells the ability to bind Zn(2+). By serial selection, sequences that exhibited various degrees of binding affinity and specificity toward Zn(2+) were enriched. None of the isolated sequences showed similarity to known Zn(2+)-binding proteins, indicating that completely novel Zn(2+)-binding peptide sequences had been isolated. By changing the protein scaffold system, we demonstrated that the Zn(2+)-binding seems to be uniquely mediated by the peptide insert and to be independent of the sequence of the carrier protein. These findings might be applied in the design of biomatrices for bioremediation purposes or in the development of sensors for detection of heavy metals.

FimH-mediated autoaggregation of Escherichia coli.

Autoaggregation is a phenomenon thought to contribute to colonization of mammalian hosts by pathogenic bacteria. Type 1 fimbriae are surface organelles of Escherichia coli that mediate d-mannose-sensitive binding to various host surfaces. This binding is conferred by the minor fimbrial component FimH. In this study, we have used random mutagenesis to identify variants of the FimH adhesin that confer the ability of E. coli to autoaggregate and settle from liquid cultures. Three separate autoaggregating clones were identified, all of which contained multiple amino acid changes located within the N-terminal receptor-binding domain of FimH. Autoaggregation could not be inhibited by mannose, but was inhibited by growth at temperatures at or below 30 degrees C. Using green fluorescent protein (GFP) as a reporter, we show that the autoaggregating clones do not mix with wild-type fimbriated cells. Electron microscopy shows that autoaggregating cells produce fimbriae with a twisted and entangled appearance. We present evidence that autoaggregating versions of FimH also occur in nature. Our results stress the highly adaptive nature of the ubiquitous FimH adhesin.

Valency conversion in the type 1 fimbrial adhesin of Escherichia coli.

FimH protein is a lectin-like adhesive subunit of type 1, or mannose-sensitive, fimbriae that are found on the surface of most Escherichia coli strains. All naturally occurring FimH variants demonstrate a conserved mannotriose-specific (i.e. multivalent) binding. Here, we demonstrate that replacement of residues 185-279 within the FimH pilin domain with a corresponding segment of the type 1C fimbrial adhesin FocH leads to a loss of the multivalent mannotriose-specific binding property accompanied by the acquisition of a distinct monomannose-specific (i.e. monovalent) binding capability. Bacteria expressing the monovalent hybrid adhesins were capable of binding strongly to uroepithelial tissue culture cells and guinea pig erythrocytes. They could not, however, agglutinate yeast or bind human buccal cells -- functions readily accomplished by the E. coli-expressing mannotriose-specific FimH variants. Based on the relative potency of inhibiting compounds of different structures, the receptor binding site within monovalent FimH-FocH adhesin has an extended structure with an overall configuration similar to that within the multivalent FimH of natural origin. The monomannose-only specific phenotype could also be invoked by a single point mutation, E89K, located within the lectin domain of FimH, but distant from the receptor binding site. The structural alterations influence the receptor-binding valency of the FimH adhesin via distal effects on the combining pocket, obviously by affecting the FimH quaternary structure.

Coordinate gene regulation by fimbriae-induced signal transduction.

Fimbriae are thread-like polymers displayed in large amounts on the bacterial surface and used by many pathogens to attach to receptors on host tissue surfaces. Fimbriae contain disulfide bridges, contrary to many Escherichia coli surface proteins produced in bulk amounts. Here we investigate whether fimbriae expression can affect expression of other genes. Analysis of gene expression in two E.coli strains, differing in the fim locus, indicated the flu gene to be affected. The flu gene encodes the antigen 43 (Ag43) surface protein, specifically involved in bacterial aggregation, and microcolony and biofilm formation. Ag43 production is repressed by the global regulator OxyR, which monitors the cell's thiol-disulfide status. Only the thiol form of OxyR represses Ag43 production. We demonstrate that production of several different disulfide-containing fimbriae results in the abolition of Ag43 production. No effect was observed in an oxyR mutant. We conclude that fimbriae expression per se constitutes a signal transduction mechanism that affects a number of unrelated genes via the thiol-disulfide status of OxyR. Thus, phase variation in fimbrial expression is coordinated with the expression of other disease- and colonization-related genes.

Biofilm formation in a hydrodynamic environment by novel fimh variants and ramifications for virulence.

Type 1 fimbriae are surface-located adhesion organelles of Escherichia coli that are directly associated with virulence of the urinary tract. They mediate D-mannose-sensitive binding to different host surfaces by way of the minor fimbrial component FimH. Naturally occurring variants of FimH that bind strongly to terminally exposed monomannose residues have been associated with a pathogenicity-adaptive phenotype that enhances E. coli colonization of extraintestinal locations such as the urinary tract. The FimH adhesin also promotes biofilm formation in a mannose-inhibitable manner on abiotic surfaces under static growth conditions. In this study, we used random mutagenesis combined with a novel selection-enrichment technique to specifically identify mutations in the FimH adhesin that confer on E. coli the ability to form biofilms under hydrodynamic flow (HDF) conditions. We identified three FimH variants from our mutant library that could mediate an HDF biofilm formation phenotype to various degrees. This phenotype was induced by the cumulative effect of multiple changes throughout the receptor-binding region of the protein. Two of the HDF biofilm-forming FimH variants were insensitive to mannose inhibition and represent novel phenotypes not previously identified in naturally occurring isolates. Characterization of our enriched clones revealed some similarities to amino acid alterations that occur in urinary tract infection (UTI) strains. Subsequent screening of a selection of UTI FimH variants demonstrated that they too could promote biofilm formation on abiotic surfaces under HDF conditions. Interestingly, the same correlation was not observed for commensal FimH variants. FimH is a multifaceted protein prone to rapid microevolution. In addition to its previously documented roles in adherence and invasion, we have now demonstrated its function in biofilm formation on abiotic surfaces subjected to HDF conditions. The study indicates that UTI FimH variants possess adaptations that enhance biofilm formation and suggests a novel role for FimH in UTIs associated with medical implants such as catheters.