T-cell brain infiltration and immature antigen-presenting cells in transgenic models of Alzheimer's disease-like cerebral amyloidosis.

Cerebral beta-amyloidosis, one of the pathological hallmarks of Alzheimer's disease (AD), elicits a well-characterised, microglia-mediated local innate immune response. In contrast, it is not clear whether cells of the adaptive immune system, in particular T-cells, react to cerebral amyloidosis in AD. Even though parenchymal T-cells have been described in post-mortem brains of AD patients, it is not known whether infiltrating T-cells are specifically recruited to the extracellular deposits of beta-amyloid, and whether they are locally activated into proliferating, effector cells upon interaction with antigen-presenting cells (APCs). To address these issues we have analysed by confocal microscopy and flow-cytometry the localisation and activation status of both T-cells and APCs in transgenic (tg) mice models of AD-like cerebral amyloidosis. Increased numbers of infiltrating T-cells were found in amyloid-burdened brain regions of tg mice, with concomitant up-regulation of endothelial adhesion molecules ICAM-1 and VCAM-1, compared to non-tg littermates. The infiltrating T-cells in tg brains did not co-localise with amyloid plaques, produced less interferon-gamma than those in controls and did not proliferate locally. Bona-fide dendritic cells were virtually absent from the brain parenchyma of both non-tg and tg mice, and APCs from tg brains showed an immature phenotype, with accumulation of MHC-II in intracellular compartments. These results indicate that cerebral amyloidosis promotes T-cell infiltration but interferes with local antigen presentation and T-cell activation. The inability of the brain immune surveillance to orchestrate a protective immune response to amyloid-beta peptide might contribute to the accumulation of amyloid in the progression of the disease.

Active vaccination with ankyrin G reduces ß-amyloid pathology in APP transgenic mice.

Serum antibodies against amyloid-ß peptide (Aß) in humans with or without diagnosis of Alzheimer's disease (AD) indicate the possibility of immune responses against brain antigens. In an unbiased screening for antibodies directed against brain proteins, we found in AD patients high serum levels of antibodies against the neuronal cytoskeletal protein ankyrin G (ankG); these correlated with slower rates of cognitive decline. Neuronal expression of ankG was higher in AD brains than in nondemented age-matched healthy control subjects. AnkG was present in exosomal vesicles, and it accumulated in ß-amyloid plaques. Active immunization with ankG of arcAß transgenic mice reduced brain ß-amyloid pathology and increased brain levels of soluble Aß(42). AnkG immunization induced a reduction in ß-amyloid pathology, also in Swedish transgenic mice(.) Anti-ankG monoclonal antibodies reduced Aß-induced loss of dendritic spines in hippocampal ArcAß organotypic cultures. Together, these data established a role for ankG in the human adaptive immune response against resident brain proteins, and they show that ankG immunization reduces brain ß-amyloid and its related neuropathology.

Bottom-up engineering of the surface roughness of nanostructured cubic zirconia to control cell adhesion.

Nanostructured cubic zirconia is a strategic material for biomedical applications since it combines superior structural and optical properties with a nanoscale morphology able to control cell adhesion and proliferation. We produced nanostructured cubic zirconia thin films at room temperature by supersonic cluster beam deposition of nanoparticles produced in the gas phase. Precise control of film roughness at the nanoscale is obtained by operating in a ballistic deposition regime. This allows one to study the influence of nanoroughness on cell adhesion, while keeping the surface chemistry constant. We evaluated cell adhesion on nanostructured zirconia with an osteoblast-like cell line using confocal laser scanning microscopy for detailed morphological and cytoskeleton studies. We demonstrated that the organization of cytoskeleton and focal adhesion formation can be controlled by varying the evolution of surface nanoroughness.

Tumour Necrosis Factor-α Inhibition Improves Stroke Outcome in a Mouse Model of Rheumatoid Arthritis.

Rheumatoid Arthritis (RA) is a chronic inflammatory disorder where incidence and severity of myocardial infarction are increased. Data on the incidence and outcome of stroke are conflicting. Thus, we investigated outcome after Ischemia/Reperfusion (I/R) brain injury in a mouse model of RA and assessed for the role of the tumour necrosis factor-α (TNF-α) inhibitor Infliximab herein. We used a TNF-α reliant mouse model of RA. RA and wildtype (WT) animals were treated with vehicle (RA/WT) or Infliximab (RA Infliximab) for 4 weeks, before undergoing I/R brain injury. RA-animals displayed larger strokes and poorer neurological performance. Immunohistochemistry on brain sections revealed increased numbers of resident and peripheral innate immune cells (microglia and macrophages); increased Blood-Brain-Barrier (BBB)-disruption; decreased levels of the tight junction proteins (TJPs) claudin-5 and occludin; increased expression of matrix-metalloproteinases (MMP)-3 and -9 and enhanced lipid peroxidation. Treatment with Infliximab corrected these alterations. We show that RA associates to worse stroke-outcome via exacerbated BBB degradation by decrease of the TJPs claudin-5 and occludin. We identified MMPs-3 and -9 and increased oxidative stress as potential mediators thereof. Increased numbers of resident and peripheral innate immune cells (microglia and macrophages) may in turn contribute to all these effects. Infliximab-treatment restored the phenotype of RA-mice to baseline. Our data provide evidence clearly linking RA to adverse stroke-outcome in mice and indicate an approved TNF-α inhibitor as a potential strategy to reduce stroke-burden in this setting.

[On the 150th birthday of César Roux (1857-1918). Memories of the life and work of an important pupil of Kocher]. / Zum 150. Geburtstag von César Roux (1857-1918). Erinnerung an Leben und Schaffen eines bedeutenden Kocher-Schülers.

César Roux was one of the few universal surgeons at the end of the 19th century who dominated all fields of surgery and influenced current surgery with his innovative spirit. Pioneering spirit and the story of the success of modern surgery are linked with his name. On the occasion of his 150th birthday, we recall the memory of this great surgeon. The personality and the history of Professor César Roux form a part of our medical and surgical heritage.

End-to-end anastomosis between a prosthesis and a vein of different diameters: a technique that maintains a straight vascular axis.

In a composite femoropopliteal bypass, the intermediate anastomosis between a vascular prosthesis and the available vein is often difficult to carry out because of a discrepancy of the diameter between the two vessels. The end-to-end anastomosis is performed by working with the elasticity of the venous tissue resulting in anastomotic kinking. A technique keeping the vascular axis straight between two vessels of different diameters and elasticity is presented.

Malignant tumors of the anus. A study of 106 cases.

This study of 106 cases of malignant tumors of the anus has shown that the diagnosis was often made late. In 15 percent of the patients the tumor was at the anal margin; in 61 percent, in the anal canal, and in 24 percent, the tumor was so extensive that its origin could not be determined clinically. In nearly half of the cases, the cancers were advanced and showed perirectal metastases. Surgical treatment was the rule, with local excision for carcinomas of the anal margin and abdominoperineal resection for tumors of the canal. The general prognosis over a period of several decades remains poor. We found a 20 percent 5 year survival rate for epidermoid carcinoma of the anal canal, excluding deaths from causes other than cancer during the follow-up period.

End-to-end anastomosis by enclosure between a prosthesis and a vessel with a significant difference in diameter.

A technique is described that allows an end-to-end anastomosis between a vascular prosthesis and a vessel that is much smaller in diameter. This procedure involves enclosing the prosthesis and the vessel while keeping the vascular axis straight without any kinking. In addition, this technique makes little demand on the extensibility of the natural tissue in order to adapt to the prosthesis, which is inextensible.

High-sensitivity electrophoretic method for the detection of Bence Jones protein and for the study of proteinuria in unconcentrated urines.

The study of proteinuria, and especially the search for Bence Jones proteins (BJP), has almost always required urine concentration. We evaluated a high-sensitivity electrophoretic method using unconcentrated urine based on colloidal gold staining. The sensitivity for the detection of BJP is further enhanced by immunofixation. Sensitivity to BJP is better than 1 mg/L and, apart from the alpha-1 microglobulin, all the proteins relevant to the classification of proteinuria can be visualized with a sensitivity of approximatively 3 mg/L.

Acetaldehyde activation of poly(ADP-ribose)polymerase in hepatocytes of mice treated in vivo.

The activities of poly(ADP-ribose) polymerase and of DNA polymerases alpha and beta and the level of cytochrome P450 were determined in mouse parenchymal liver cells 5 h after treatment with 0.1, 0.3, 1.0, and 3.0 mumole of acetaldehyde. Injection with 1.0 and 3.0 mumole of acetaldehyde induced an increase in poly(ADP-ribose) polymerase activity and in the P450 level, but had no effect on DNA polymerases. The stimulation of poly(ADP-ribose) polymerase activity can be used as an index of induced DNA damage. The possibility of using this experimental approach with other cells derived from mice treated in vivo with different xenobiotics is discussed.

Analysis of 1930 bedridden patients in the internal medical sector of the emergency department of a large city hospital: appropriate and non-appropriate admission.

This paper discusses criterion for the appropriateness of admission to the hospitalization ward in the internal medical sector of the emergency department, and analyses the bedridden patients in the emergency department of the major hospital in the city of Genoa. The analysis covers 1930 patients, for which considerations are made, globally and separately in two different age groups, as to the appropriateness of admission to the hospitalization ward of the emergency department, the occurrence of subjective urgencies and objective instabilities, and progression subsequent to hospitalization (discharge, transfer into other hospital wards, decease). The most significant results of the analysis were the following: (1) no significant difference was found between younger and older patients regarding appropriateness of admission; (2) in cases of appropriate admission subjective urgency was clearly prevalent in relation to objective instability, the latter being much more frequent in the older age group; (3) a lack of self-sufficiency and the absence of adequate family support were important factors regarding inappropriate admission of older patients; (4) the greater frequency of objective instability in the older patients-as well as a lack of self-sufficiency-was the major factor in their greater length of stay in the emergency department. These results challenge the misconceived but diffused conviction that there is widespread mishandling of the elderly regarding admission to the emergency department, while at the same time stresses the need for alternative services and structures concerning hospital admission of older patients.

[Chronic saphenous venous access: an interesting alternative in the case of vena cava superior syndrome]. / Chronischer venöser Zugang uber die Vena saphena. Eine interessante Alternative im Falle des Vena-cava-superior-Syndroms.

An easy venous access improves the quality of life of patients who need prolonged intravenous therapy. In the case of vena cava superior syndrome the classic access in the jugular or subclavian vein can be difficult or even impossible. We report on seven implantations of Port-a-Cath in the inferior vena cava for patients presenting contra-indications to classic venous access to the vena cava superior (five cases of vena cava superior compression syndrome, one tracheostomy and one extended tumor of thoracic wall). We describe the operative technique and we analyze the indications, the results and the complications of this rarely used technique.

[Quality of life of vascular disease patients following amputation]. / La qualité de vie des patients vasculaires amputés.

STUDY AIM: The purpose of this study was to assess the quality of life following lower limb amputation for vascular disease. PATIENTS AND METHODS: Thirty-six vascular patients operated on for 40 major amputations were reviewed to assess demographic and clinical characteristics, possibilities of prosthesis, perception of health problems and social adaptation. These data were correlated with general satisfaction and quality of life ratings, using the Nottingham Health Profile. RESULTS: The average stay in hospital was 109 days. Thirteen patients (36%) died in hospital, 23 others (64%) were discharged, but only ten patients (28%) were able to go back home. The global mortality rate at 1 year was 44%. Eighteen patients (78%) were initially fitted but only seven (30%) were fully independent. Eight patients only (35%) were satisfied at the end of treatment. Patient's satisfaction was influenced by the level of his amputation, the presence of residual pain and by his mobility, but it was independent of prosthetic equipment. CONCLUSION: Quality of life of vascular amputated patients is poor and marked by persistent pain and considerable handicaps in mobility, limiting social activities and relationship. The patients' satisfaction and quality of life appear to be related to their ability to manage social relations. Amputation should be considered as the first step towards rehabilitation and not the end of the treatment. It is only through a multidisciplinary approach that the quality of life of amputated patients can be improved.

[Outcome of nonspecific right iliac fossa pain syndromes]. / Devenir des syndromes douloureux non spécifiques de la fosse iliaque droite.

One-third of all cases of abdominal pain and a quarter of cases of right iliac fossa pain urgently admitted to hospital leave hospital with no precise diagnosis. Based on a series of 400 patients hospitalised for right iliac fossa pain, comprising 107 cases with no identified aetiology, this prospective study was designed to assess the medium-term outcome of these patients, with or without surgical exploration. 67 cases were reviewed at five years. No major diagnosis was missed. Over this 5-year period, 30 patients (45%) experienced another episode of abdominal pain. Among the third of patients (21 cases, 31%) reviewed for another episode of right iliac fossa pain, 7 were readmitted to hospital, with 5 operations, for histologically confirmed acute appendicitis in 3 cases (5% of the series). The patient and his attending physician must be informed of the nonspecific diagnosis established during the first hospitalisation. There is no significant evidence to suggest a psychological component in the recurrent nature of the pain. Cancer must be formally excluded in patients over the age of 50. When surgical exploration is performed, nowadays by laparoscopy, appendicectomy is recommended. This procedure does not decrease the risk of recurrent pain, but confirms the real absence of histopathological abnormality and decreases the number of subsequent hospitalisations.

Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder with exocrine pancreatic insufficiency, bone marrow failure and skeletal abnormalities. Patients frequently present failure to thrive, susceptibility to infections and short stature. A persistent or intermittent neutropenia occurs in 88-100% of patients. Bone marrow biopsy usually reveals a hypoplastic specimen with varying degrees of hypoplasia and fat infiltration. Some patients may develop myeloblastic syndrome and acute myeloblastic leukemia. The genetic defect in SDS has been identified in 2002. The osteoporosis is increased in patients with SDS, and also, bone malformations are included among the primary characteristics of the syndrome. The severity and location change with age and sexes. The typical characteristics include the following: secondary ossification centers delayed appearance, metaphysis enlargement and irregularity (very common in childhood, particularly in coastal and femur), growth cartilage progressive thinning and irregularity (possibly asymmetric growth), generalized osteopenia with cortical thinning. We describe a clinical case regarding an SDS patient with severe bone abnormalities and treated surgically for corrective osteotomy. The persistent or intermittent neutropenia that characterized this disease and the consequent risk of infection is a contraindication for short stature correction and limbs lengthening.

Portable double-sided laser-heating system for Mössbauer spectroscopy and X-ray diffraction experiments at synchrotron facilities with diamond anvil cells.

The diamond anvil cell (DAC) technique coupled with laser heating is a major method for studying materials statically at multimegabar pressures and at high temperatures. Recent progress in experimental techniques, especially in high-pressure single crystal X-ray diffraction, requires portable laser heating systems which are able to heat and move the DAC during data collection. We have developed a double-sided laser heating system for DACs which can be mounted within a rather small (~0.1 m(2)) area and has a weight of ~12 kg. The system is easily transferable between different in-house or synchrotron facilities and can be assembled and set up within a few hours. The system was successfully tested at the High Pressure Station of White Beam (ID09a) and Nuclear Resonance (ID18) beamlines of the European Synchrotron Radiation Facility. We demonstrate examples of application of the system to a single crystal X-ray diffraction investigation of (Mg(0.87),Fe(3+) (0.09),Fe(2+) (0.04))(Si(0.89),Al(0.11))O(3) perovskite (ID09a) and a Synchrotron Mössbauer Source (SMS) study of (Mg(0.8)Fe(0.2))O ferropericlase (ID18).