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.

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.

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).

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.

[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.

Crystallization on heating and complex phase behavior of alpha-cyclodextrin solutions.

Solutions composed of alpha-cyclodextrin (alpha-CD), water, and various methylpyridines, in particular, 4-methylpyridine (4MP), undergo reversible liquid-solid transitions upon heating, the crystalline solid phases undergoing further phase transformations at higher temperatures. This unusual behavior has been characterized by an ensemble of measurements, including solubility, differential scanning calorimetry, quasielastic neutron scattering, as well as x-ray powder diffraction. For the alpha-CD/4MP system five crystalline phases have been identified. The unit cell parameters and corresponding changes with temperature indicate a scenario for the crystallization process. A simple model is proposed that mimics the observed disorder-order transition.

Krukenberg's tumor, three years after a colic carcinoma.

We report a case of left ovarian Krukenberg's tumor in a 65 year-old patient, three years after resection of a colonic carcinoma (pT3, G2, pN1, Stage 3, Dukes C). The case is briefly discussed with reference to the literature. Krukenberg's tumor usually occurs in younger patients, with a peak frequency before 40 years. Both ovaries are involved in 90% of cases. Pathogenetically the ovarian involvement arises either from hematogenous, lymphatic spreading or from contiguous extension from the primary colonic tumor. There may be some anatomic predispositions such as utero-ovarian vessel anastomosis in the ligamentum latum or by peritoneal adhesions.

[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.

[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.

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.

[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.

[Use of the deep femoral artery as the anastomotic site in proximal or distal bypass. Indications, technique, results of a series of 19 cases]. / Utilisation de l'artère fémorale profonde comme site d'anastomose dans les pontages proximaux ou distaux. Indications, technique, résultats d'une série de 19 cas.

Atherosclerosis predominantly affects the ilio-superficial femoral axis, and tends to spare the deep femoral artery which can offer excellent outflow for proximal reconstructions for occlusive vascular disease of the lower limbs. Often symptoms are relieved and ischemic lesions can heal. The deep femoral artery can also provide good, pulsatile inflow for distal reconstructions when it is desirable to avoid the groin (either because of multiple previous dissections or because of infection). Occasionally two-level sequential bypasses to and from the deep femoral artery are required for multilevel disease where the groin is to be avoided. Over the past 4 years we have performed 190 arterial reconstructions (41 central, 125 distal and 24 sequential two-level procedures). 19 times the proximal, distal or intermediate anastomosis was on the deep femoral artery. Short- and long-term results were good in these difficult patients, with relief of symptoms or significant improvement in most patients. Two major (and no minor) amputations were ultimately required. Arterial reconstructions using the deep femoral artery cannot only salvage many limbs, but offer good symptomatic relief in patients who are not suitable for usual reconstructive procedures.

[Transluminal dilatation by surgeons. Technique, results and advantages]. / La dilatation transluminale faite par les chirurgiens. Technique, résultats et avantages.

From January 1990 to December 1992, 25 balloon angioplasties were performed in the Department of Surgery, La Chaux-de-Fonds, Switzerland. The indications were claudication in 19, and limb salvage in 6 patients. In 4 patients, the stenosis was dilated in association with a femoropopliteal bypass (2 patients) or an intraluminal stent (2 patients). The follow-up period ranged from 3 to 36 months with a cumulated patency rate of 81%. Percutaneous transluminal angioplasty for atherosclerotic lesions of the lower extremity is associated with a good success rate. Important variables influencing patency include indications, site and extent of lesion and whether the responsible lesion is stenotic or occlusive. The advent of endovascular surgery has transformed the landscape of vascular disease management. In so doing it has confused the border between the various medical specialties. The decision to use transluminal angioplasty, should be a joint decision between surgeon and radiologist, but transluminal angioplasty should be part of the vascular surgeon's armamentarium.

[Laparoscopy: obstacle or revolution in the development of surgery?]. / La laparoscopie: entrave ou révolution de la formation de chirurgie?

Laparoscopy is a new fascinating technique. However, after the first wave of enthusiasm, laparoscopy currently raises different problems related with surgical training. A national survey concerning laparoscopy and its teaching was sent to every surgeon-in-chief, chief resident and resident of all Swiss teaching hospitals. Surgical training is nowadays an important problem in Switzerland. Our survey revealed that laparoscopy intensifies this problem: a specific training in laparoscopy is desired by all surgeons and has to take place in the Swiss Board of Surgery (FMH). A preliminary experience of conventional surgery is desirable. Then a laparoscopic training should start on experimental certified models and be applied progressively on patients in attendance with a trained surgeon.

[Treatment of irreducible hiatal hernia with reflux esophagitis by Collis-Niessen gastroplasty-fundoplication. Indications, technique, results of a series of 17 cases]. / Traitement de la hernie hiatale non réductible avec oesophagite de reflux par gastroplastie-fundoplication selon Collis-Nissen. Indications, technique, résultats d'une série de 17 cas.

Hiatus hernia with reflux can be asymptomatic or can lead to severe, complicated esophagitis or even to metaplasia, dysplasia and carcinoma. Ideally all refluxing patients with esophagitis who are not easily and completely controlled with medical therapy should undergo anti-reflux surgery before complications such as ulcers, stricture or columnar metaplasia (Barrett's esophagus) occur. When esophagitis is long-lasting or severe, shortening of the esophagus is common. In such cases the esophagus must be "lengthened" before an anti-reflux procedure can be performed safely. This is the Collis gastroplasty. We have performed 17 Collis-Nissen procedures over 5 years for complicated gastroesophageal reflux disease (GERD). Results were good to excellent in 8 cases, satisfactory in 6 and poor in 3. We conclude that a complete preoperative workup with esophagoscopy (and biopsies), 24-hour pH monitoring and esophageal manometry must be performed in all patients with complicated GERD to allow the best operative procedure to be chosen (gastroplasty-fundoplication, resection or total duodenal diversion). The role of alkaline reflux is also discussed.