GLOS and HARM in patients with transient neurovascular symptoms with and without ischemic infarction.

BACKGROUND AND PURPOSE: Gadolinium leakage in ocular structures (GLOS) on fluid attenuated inversion recovery images (FLAIR) is a novel imaging marker in acute ischemic stroke and other neurological disorders. METHODS: In patients with transient neurovascular symptoms who underwent repeated MRI with intravenous contrast agent administration, the presence of acute ischemic lesions on diffusion-weighted images (DWI) as well as the frequency and pattern of blood-brain barrier and blood-retina barrier impairment as demonstrated by the hyperintense acute reperfusion marker (HARM) and GLOS respectively on postcontrast FLAIR were evaluated. RESULTS: Overall 28 patients with transient neurovascular symptoms (median age 70.5 years; 18 (64.3%) male) were included. Follow-up MRI was performed within 35 (IQR 21-47) hours after the initial MRI. On DWI, acute ischemic lesions were observed in 22 (78.6%). On contrast-enhanced FLAIR, GLOS was observed in 12 (42.9%) patients: in 1 (3.6%) only in the anterior chamber, and in 11 (39.3%) in the anterior chamber and vitreous body. HARM was observed in 3 (10.7%) patients. In one patient without ischemic lesion on DWI or HARM on FLAIR, GLOS was observed in the anterior chamber and vitreous body. Presence of GLOS was associated with higher age (p = 0.04) and detection of HARM (p = 0.03). CONCLUSIONS: In patients with transient neurovascular symptoms, GLOS is a frequent finding and associated with HARM on contrast-enhanced FLAIR. As GLOS was observed in one patient without an ischemic lesion or HARM, it might be useful as an additional imaging marker.

The economic benefit of timely, adequate, and adherence to Parkinson's disease treatment: the Value of Treatment Project 2.

BACKGROUND: Parkinson's disease (PD) is a chronic progressive neurological disorder with a high psychosocial and economic burden. As part of the European Brain Council (EBC)-led Value of Treatment project, this study aimed to capture the economic benefit of timely, adequate, and adherence to PD treatment. METHODS: The EBC Value of Treatment Initiative combined different stakeholders to identify unmet needs in the patients' journey according to Rotterdam methodology. The economic evaluation focused on three major topics identified as major gaps: start of treatment; best treatment for advanced disease; and adherence to treatment. Two separate healthcare systems (Germany and the UK) were chosen. Cost-effectiveness was determined by using decision-analytical modelling approaches. Effectiveness was expressed as quality-adjusted life-years (QALYs) gained and incremental cost-effectiveness ratio (ICER). RESULTS: Treatment intervention in PD was found to be cost-effective regardless of the initial health state of the patient receiving the treatment. Cost savings were between -€1000 and -€5400 with 0.10 QALY gain and -€1800 and -€7600 with 0.10 QALY gain for Germany and the UK, respectively. Treatment remains cost-effective within the National Institute for Health and Care Excellence thresholds. Availability of adequate treatment to more patients was also found to be cost-effective, with an ICER of €15,000-€32,600 across country settings. Achieving the target adherence to treatment would generate cost-savings of €239,000-€576,000 (Germany) and €917,000-€2,980.000 (UK) for every 1,000 patients treated adequately. CONCLUSIONS: The analyses confirmed that timely, adequate, and adherence to PD treatment will not only improve care of the patients but is also cost-effective across healthcare systems. Further studies with a distinct identification of gaps in care are necessary to develop better and affordable care.

Hippocampal infarction: Identification of three new types.

BACKGROUND AND PURPOSE: Hippocampal infarction (HI) is common but yet still not comprehensively studied. In the present study, we aimed to identify novel HI patterns and to describe additional ischemic lesions outside the hippocampus to draw conclusions regarding the underlying vessel occlusion. METHODS: In 222 patients (mean age 69.9 (±13.6) years; 129 (58.1%) male, 93 (41.9%) female) with HI, diffusion-weighted images were analyzed with emphasis on HI patterns and associated ischemic lesions outside the hippocampus. HI were classified as type 1 (complete), 2 (lateral), 3 (dorsal), and 4 (circumscribed). Further possible HI patterns were defined and classified as type 5 (ventral), 6 (ventrolateral), and 7 (dorsolateral). RESULTS: Unilateral HI was found in 218 (98.2%) patients. In these, type 5 and 6 were identified in 5 (2.3%) patients, and type 7 in 8 (3.7%) patients respectively. Type 1 was found in 62 (28.4%), 2 in 53 (24.3%), 3 in 57 (26.1%), and 4 in 28 (12.8%) patients. Further ischemic lesions were found in the territory of the anterior cerebral artery (3.6%), middle cerebral artery (14.9%), anterior choroidal artery (AChA) (7.2%), posterior cerebral artery (89.6%), and in the brainstem (6.3%) and cerebellum (20.3%). Type 5 and 6 were significantly associated with acute ischemic lesions in the AChA territory (6/10 (60%) vs. 11/200 (5.5%), P<0.001). CONCLUSIONS: We identified three novel HI types. Probably, type 5 and 6 can be attributed to occlusion of the AChA. Overall, these HI types are rare, possibly due to a better collateralization in the case of AChA occlusion.

[Potential for intervention of private health insurers in discharge management using the example of stroke patients]. / Interventionspotenzial einer privaten Krankenversicherung beim Entlassmanagement am Beispiel von Schlaganfall-Patienten.

The study reveals that stroke patients today can still experience gaps in the provision of healthcare and fragmented therapy. This is often the case on transferral from the inpatient to outpatient sector, causing complications that could be avoided by means of good discharge management across all sectors. Private health insurance can actively support and positively influence the treatment process in the form of case management. Individual contact with stroke patients and their relatives allows for early planning and organisation of the next steps, and offers patients the support they need during a difficult phase of life.

[Glomuvenous malformations]. / Glomuvenöse Malformationen.

SYMPTOMS: A patient presented suffering from neural pain in the medial foot for a period of over 20 years. DIAGNOSIS: Diagnostic showed a widely spread soft-tissue tumor consisting of confluent glomuvenous malformations that was responsible for the immense pain syndrome.The solitary or multiform-appearing knots are not compressible and manifest as the characteristic syndromes of regional pain, sensitivity to coldness, or local pressure pain. Alternatively, the patient could also be completely symptom-free. TREATMENT: Because of the dimension of the tumor and the degree of suffering, a radical resection with simultaneous microsurgical reconstruction was carried out. Twelve weeks postoperatively, healing of the flap stabilized, the foot is fully weight-bearing, and the patient is pain-free.

[Cutaneous infection with Aggregatibacter actinomycetemcomitans]. / Kutane Infektion mit Aggregatibacter actinomycetemcomitans.

BACKGROUND: Aggregatibacter actinomycetemcomitans is a small, gram-negative, non-motile, coccobacillus. Aggregatibacter actinomycetemcomitans is known to cause periodontal disease and to be associated with actinomycosis. CASE REPORT: We report a patient developed a chronic wound following trauma about the right heel. The lesion resolved after oral antibiotic therapy with cefpodoxime und surgical debridement. Bacterial cultures grew abundant Aggregatibacter actinomycetemcomitans, but no actinomyces species. OBJECTIVE: The importance of Aggregatibacter actinomycetemcomitans in chronic wounds needs to be explored.

[Polytrauma with pelvic fractures and severe thoracic trauma: does the timing of definitive pelvic fracture stabilization affect the clinical course?]. / Polytrauma mit Beckenfraktur und schwerem Thoraxtrauma: Hat der Zeitpunkt der definitiven Beckenfrakturstabilisierung Einfluss auf den klinischen Verlauf?

BACKGROUND: The aim of this study was to investigate the influence of the surgical timing in patients with pelvic fractures and severe chest trauma on the clinical course, especially on postoperative lung function. METHODS: A total of 47 patients were included in a prospective dual observational study. The study investigated the clinical course depending on the time of operation based on the functional lung parameters, SAPS II, SOFA and total hospital stay. RESULTS: The average ISS was 32±6, PTS was 34±11 and TTSS was 9±3 points. The pelvic fractures were stabilized definitively after an average of 7±2 days. The early stabilization correlated significantly with a lower TTSS and SAPS II on admission (p<0.05), shorter time of ventilation (p<0.05) and stay in the intensive care unit (p<0.01) as well as the decreased need for packed red blood cells (p<0.01). CONCLUSIONS: In this study patients with pelvic fractures and thoracic trauma benefited positively from an earlier definitive pelvic fracture stabilization with respect to a shorter time of ventilation and stay in the intensive care unit due to a lower need for red cell concentrates.

[Ligament healing results after type C pelvic ring fractures. Results of triangular vertebropelvic support]. / Ligamentäre Ausheilungsergebnisse nach Beckenringfrakturen Typ C. Ergebnisse der triangulären vertebropelvinen Abstützung.

BACKGROUND: Posterior pelvic ring fractures are often associated with injuries of lumbopelvic soft tissue structures. The aim of this prospective MR study was to examine whether ruptured iliolumbal ligaments could be diagnosed in types B and C pelvic ring fractures. The influence of triangular lumbopelvic stabilization (TLPS) was also investigated with respect to stiffening of the lumbopelvic region. MATERIAL AND METHODS: Using a 1.5 Tesla MRI, 20 patients with types B and C fractures were examined to identify ruptured iliolumbal ligaments. In a retrospective study of 30 patients previously stabilized with a TLPS, pain scores, clinical instability testing and measuring of the segmental dislocation in extension, flexion and lateral flexion based on x-rays were also investigated. RESULTS: Of the patients 3 (1 type B, 2 type C fractures) had incompletely ruptured iliolumbal ligaments. In five patients pain intensity and localization could be significantly correlated with clinical instability of the lumbopelvic region, segmental hypermobility and instability. CONCLUSION: Pelvic ring fractures types B and C can be associated with ruptured iliolumbal ligaments. Lumbopelvic instability can be correlated with early implant loosening of TLPS.

Asymmetrical Gadolinium Leakage in Ocular Structures in Stroke Due to Internal Carotid Artery Stenosis or Occlusion.

PURPOSE: Gadolinium leakage in ocular structures (GLOS) on fluid-attenuated inversion recovery images (FLAIR) is a novel imaging marker in acute ischemic stroke. The present study sought to investigate the frequency and pattern of blood-retina barrier impairment in acute ischemic stroke due to internal carotid artery (ICA) stenosis or occlusion as demonstrated by GLOS. METHODS: From a magnetic resonance imaging (MRI) report database patients were identified with acute ischemic stroke due to ICA stenosis/occlusion who underwent repeated MRI with intravenous contrast agent administration and FLAIR and MR angiography (MRA). On FLAIR the presence of GLOS was noted in the vitreous body. RESULTS: Overall 51 patients with a median age of 70 years (interquartile range, IQR 63-77 years) were included. Of these, 22 (43.1%) patients had an ICA stenosis and 29 (56.9%) an ICA occlusion. On contrast-enhanced FLAIR, GLOS was observed in 29 (56.9%) patients: in 7 (13.7%) unilateral, in 15 (68.2%) bilateral asymmetrical and in 7 (31.8%) bilateral symmetrical. In unilateral asymmetrical GLOS, more pronounced enhancement was always found ipsilateral to ICA stenosis/occlusion. In 4 (5.9%) patients with asymmetrical GLOS a pre-existing signal increase in the vitreous body was found on native FLAIR. The presence of GLOS was associated with an impaired collateralization through the circle of Willis (p < 0.001) and external carotid artery branches (p = 0.03). CONCLUSION: In patients with ischemic stroke due to ICA stenosis/occlusion, GLOS is frequent, commonly unilateral or bilateral asymmetrical, and in some patients associated with pre-existing ocular signal abnormalities. An insufficient collateralization may contribute to the development of unilateral/asymmetrical GLOS.

MHC-linked protection from diabetes dissociated from clonal deletion of T cells.

The I-E molecule of the major histocompatibility complex (MHC) can prevent the spontaneous development of diabetes in nonobese diabetic (NOD) mice. The mechanism of this protection has been investigated by breeding wild-type and promoter-mutated E kappa alpha transgenes onto the NOD genetic background. Animals carrying the various mutated transgenes expressed I-E on different subsets of immunocompetent cells, and thus cells important for the I-E protective effect could be identified. Although the wild-type transgene prevented the infiltration of lymphocytes into pancreatic islets, none of the mutants did. However, all of the transgenes could mediate the intrathymic elimination of T cells bearing antigen receptors with variable regions that recognize I-E. Thus, the I-E molecule does not protect NOD mice from diabetes simply by inducing the deletion of self-reactive T cells.

Transgenic mice with I-A on islet cells are normoglycemic but immunologically intolerant.

Insulin-dependent diabetes mellitus (IDDM) is caused by a specific loss of the insulin-producing beta cells from pancreatic Langerhans islets. It has been proposed that aberrant expression of major histocompatibility complex (MHC) class II molecules on these cells could be a triggering factor for their autoimmune destruction. This proposal was tested in transgenic mice that express allogeneic or syngeneic class II molecules on the surface of islet cells at a level comparable with that normally found on resting B lymphocytes. These animals do not develop diabetes, nor is lymphocyte infiltration of the islets observed. This immunological inactivity does not result from tolerance to the "foreign" class II molecules.

Gadolinium leakage in ocular structures: A novel MRI finding in transient global amnesia.

BACKGROUND AND PURPOSE: We investigated the frequency and pattern of blood-brain barrier as well as blood-retina barrier impairment in transient global amnesia (TGA) as demonstrated by hyperintense acute reperfusion marker (HARM) and gadolinium leakage in ocular structures (GLOS) respectively on fluid attenuated inversion recovery images (FLAIR). METHODS: Patients with TGA who underwent repeated MRI after intravenous contrast agent administration were identified and the presence of GLOS in the anterior chamber and vitreous body and HARM noted on FLAIR. RESULTS: Overall 10 patients (IQR 64.25-71.75 years; 4 (40%) patients were male) were included. On contrast-enhanced FLAIR, GLOS was observed in 3 (30%) patients; in all of these in the anterior chamber and vitreous body as well as bilateral and symmetrical. HARM was observed in none of the patients. Frequency of hippocampal DWI lesions, as well as extent of age related white matter lesions did not differ significantly between patients with and without GLOS. CONCLUSIONS: In contrast to HARM, GLOS is a relatively common finding in TGA patients. As GLOS is thought to share its pathophysiology at least to some extent with HARM and is associated with HARM in ischemic stroke, it might be used as surrogate marker for blood-brain barrier impairment in TGA.

Lateral compression type B 2-1 pelvic ring fractures in young patients do not require surgery.

PURPOSE: According to Young and Burgess, type B 2-1 pelvic fractures are a type of lateral compression fracture (LC-1) and are the most common pelvic injury at all ages. Although they are considered unstable in rotation and despite biomechanical recommendations for anterior stabilization, most authors recommend non-operative treatment. However, studies comparing outcomes and complications regarding operative versus non-operative treatment are still scarce. METHODS: Seventy-one patients aged under 65 years with a type B 2-1 pelvic fracture were treated between 2006 and 2011. Patients in Group I (n = 35) were treated non-operatively and patients in Group II (n = 36) were treated operatively. Postoperative complications, clinical course, and follow-up (VAS for Pain, SF 36, EQ-5D) of at least 1 year postoperatively were evaluated. RESULTS: Our data show that operatively treated patients had a significantly higher complication rate. Preoperatively, the only significant difference between the non-operative and operative groups was the amount of anterior fracture dislocation and the presence of an isolated pelvic ring fracture. In the postoperative follow-up, no significant differences were found regarding pain or quality of life. CONCLUSION: Type B 2-1 pelvic ring fractures in young patients should be treated non-operatively.

Gene conversion of major histocompatibility complex genes in the mouse spermatogenesis is a premeiotic event.

The molecular genetic mechanism of gene conversion in higher eukaryotes remains unknown. We find it of considerable interest to determine when during spermatogenesis gene conversion occurs. We have therefore purified pachytene spermatocytes and haploid spermatocytes from adult mice and analyzed these fractions for the presence of gene conversion products resulting from the transfer between the major histocompatibility complex class II genes Ebd and Abk in a polymerase chain reaction assay. We have further isolated spermatogenic cells from prepubescent mice and analyzed them for the presence of the same gene conversion products. We can detect gene conversion products in testis cells as early as in 8-d-old mice where the only existing spermatogenic cells are spermatogonia. The frequency of gene conversion products remains the same as the cells reach meiosis in 18-d-old mice, and is unchanged after meiosis is completed in haploid spermatocytes. Gene conversion of this specific fragment therefore appears to be a premeiotic event and, consequently, relies on genetic mechanisms other than normal meiotic recombination.

Isolated punctuate hippocampal infarction and transient global amnesia are indistinguishable by means of MRI.

Background Small punctuate lesions in the hippocampus on diffusion-weighted images are a typical finding in transient global amnesia. Consequently, it has been suggested that diffusion-weighted images findings might corroborate the diagnosis of transient global amnesia. However, isolated punctuate hippocampal infarction might be a differential diagnosis of transient global amnesia. Aim Evaluation of isolated punctuate hippocampal infarction frequency and comparison of its clinical presentation and MRI findings to transient global amnesia. Methods From an MRI database, we identified 10 patients with isolated punctuate hippocampal infarction and compared these to 12 patients with transient global amnesia with diffusion-weighted images lesion with regard to clinical symptoms and MRI findings. Results Disorientation and memory deficits were more common in transient global amnesia patients, whereas dysphasia/aphasia and vertigo were more common in hippocampal infarction patients. MRI findings in isolated punctuate hippocampal infarction and transient global amnesia did not differ significantly, neither regarding the affected hemisphere, lesion distribution, size, nor relative ADC values. Conclusions Differentiation of isolated punctuate hippocampal infarction and transient global amnesia based on neuroimaging findings is not possible. Thus, in the case of isolated punctuate hippocampal diffusion-weighted images lesions the final diagnosis of hippocampal infarction or transient global amnesia should be based on the clinical presentation.

HLA-DR-DQ haplotypes defined by restriction fragment analysis. Correlation to serology.

Through the analysis of RFLP (restriction fragment length polymorphism) of the HLA-DR beta, -DQ alpha, and -DQ beta genes from 70 serologically well-characterized individuals, we have established unique HLA-DR-DQ RFLP haplotypes correlating to all of the DR1-w14 specificities. The RFLP of DR beta, DQ alpha, and DQ beta genes is very high using the restriction enzyme TaqI and 21 DR-DQ RFLP haplotypes were defined with this restriction enzyme. Our analysis confirms the strong linkage disequilibrium between alleles in the DR and DQ loci. DR beta RFLP indicates a common ancestor for the DR alleles within either of the supertypic DRw52 and DRw53 specificities. The DQ beta gene shows a high degree of RFLP, and the RFLP alleles partly reflect the serologic DQw1-w3 specificities. The results presented here also demonstrate the heterogeneity of DRw6 (DRw13 and DRw14) associated haplotypes, and the DRw13 related Dw18 and Dw19 specificities were found to have distinct DR-DQ haplotypes. The DQw1 positive haplotypes DR1, 2, w10, w13, and w14 are related with regard to DQ alpha and DQ beta RFLPs and the DRw52 positive haplotypes DR3, w11, and w12, as well as the DRw53 positive haplotypes DR4, 7, and w9, are related with regard to DR beta and DQ alpha RFLPs. These findings indicate that polymorphic sequences around the DQ alpha gene are associated with DR beta and DQ beta polymorphism, which suggests a location of the DQ alpha gene between DR beta and DQ beta.

Genomic hybridization with class II transplantation antigen cDNA probes as a complementary technique in tissue typing.

Hybridizations of HLA-DR and DC transplantation antigen beta chain cDNA probes to restriction enzyme digested genomic DNA were examined in regard to their potential in tissue typing. DNA from cells, typed by cellular techniques to be homozygous for the specificities Dw 1 to 8, gives rise to unique fragment patterns for each specificity. Hybridizations to DNA from unrelated individuals serologically typed to be DR identical occasionally reveal genetic differences in the class II antigen region, notably with the DC beta cDNA probe. In contrast, hybridizations to DNA from monozygotic twins displayed completely identical patterns with both types of probes. From these data it seems reasonable to conclude that genomic hybridizations with class II antigen probes will be useful in the definition of new class II antigen loci and alleles, in determination of paternity, in studies of class II antigen linked diseases and as a complementary method in conventional tissue typing.

Enantioselective hydrolysis of racemic naproxen nitrile and naproxen amide to S-naproxen by new bacterial isolates.

Bacteria were enriched from soil samples with succinate as a carbon source and racemic naproxen nitrile [2-(6-methoxy-2-naphthyl)propionitrile] as sole source of nitrogen. Since naproxen nitrile was only poorly soluble in water media amended with different water-immiscible organic phases were used for the enrichments. With pristane (2,6,10,14-tetramethylpentadecane) as the organic phase two bacterial strains were isolated (strain C3II and strain MP50) which were identified as rhodococci. Cells of both strains converted naproxen nitrile via naproxen amide to naproxen. From racemic naproxen nitrile Rhodococcus sp. C3II formed S-naproxen amide and subsequently S-naproxen. Racemic naproxen amide was hydrolysed to S-naproxen. Rhodococcus sp. MP50 converted racemic naproxen nitrile predominantly to R-naproxen amide and racemic naproxen amide to S-naproxen. With both strains racemic naproxen amide was converted to S-naproxen with an enantiomeric excess > 99% at a conversion rate up to 80% of the theoretical value. In strain C3II the enzymes which hydrolysed naproxen nitrile and naproxen amide were present only at a low constitutive level. In contrast, in Rhodococcus sp. MP50 these activities were induced when grown in the presence of various nitriles.

Limits of peritoneal cytokine measurements during abdominal lavage treatment for intraabdominal sepsis.

BACKGROUND: Monitoring of peritoneal cytokine concentrations of tumor necrosis factor (TNF)-alpha was recommended for early detection of severe postoperative complications. In the present study the clinical application of cytokine monitoring was examined in the treatment course of severe peritonitis. METHODS: Nineteen patients with secondary peritonitis were followed up during 75 abdominal lavages. Serum and peritoneal interleukin (IL)-6, IL-8, and IL-10 and TNF-alpha were measured before the surgical intervention, after 1 hour, 3 hours, 6 hours, and 24 hours. Additionally, cardiorespiratory parameters, osmolarity, C-reactive protein, and total leucocyte count were recorded. RESULTS: Serum and peritoneal cytokine concentrations did not correlate to each other as well as to the observed cardiorespiratory parameters. Peritoneal cytokine concentrations were 10- to 1000-fold higher to serum concentrations and showed an intermittent wash out. There were no differences in determined cytokine concentrations between survivors and nonsurvivors. CONCLUSIONS: Once elevated, peritoneal cytokine measurements offer no new diagnostic or prognostic tool in abdominal lavage peritonitis treatment.

DNA damage caused by etoposide and gamma-irradiation induces gene conversion of the MHC in a mouse non-germline testis cell line.

We have explored the effects of gamma-irradiation and etoposide on the gene conversion frequency between the endogenous major histocompatibility complex class II genes Abk and Ebd in a mouse testis cell line of non-germline origin with a polymerase chain reaction assay. Both gamma-rays and etoposide were shown to increase the gene conversion frequency with up to 15-fold compared to untreated cells. Etoposide, which is an agent that stabilise a cleavable complex between DNA and DNA topoisomerase II, shows an increased induction of gene conversion events with increased dose of etoposide. Cells treated with gamma-rays, which induce strand breaks, had an increased gene conversion frequency when they were subjected to low doses of irradiation, but increasing doses of irradiation did not lead to an increase of gene conversion events, which might reflect differences in the repair process depending on the extent and nature of the DNA damage. These results where DNA damage was shown to be able to induce gene conversion of endogenous genes in mouse testis cells suggests that the DNA repair system could be involved in the molecular genetic mechanism that results in gene conversion in higher eukaryotes like mammals.