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Biomedical subjects

P Simon

Publications and source records attributed to P Simon.

At least 37 records · Page 2Linked to original sources

The World Anti-Doping Code 2003--consequences for physicians associated with elite athletes.

The purpose of the World Anti-Doping Code 2003 and the 2004 Prohibited List is to create a universal international standard to fight doping in competitive sports. The result of this is a whole series of changes for doctors with regard to their work with competitive athletes. The revised definition of doping now includes physicians in the group of persons who can fulfil the elements of a doping offence. Moreover, the mere possession of substances appearing on the Prohibited List represents a violation of anti-doping regulations. The 2004 Prohibited List includes several changes to the Olympic Movement List from 2003. Caffeine, for example, was removed from the list. Cannabinoids, on the other hand, are now prohibited in competition for all sports. The same is true for all forms of glucocorticosteroids. Therapeutic use exemptions in an abbreviated process are possible for the administration of glucocorticosteroids by non-systemic routes, as well as inhalative therapy with the beta-2-agonists formoterol, salbutamol, salmeterol, and termbutalin. In other cases, a therapeutic use exemption is possible using a standard application process. Further changes will become effective in the 2005 Prohibited List. In 2005, it is essential that beta-2-agonists are prohibited in and out of competition. HCG and LH are prohibited for all athletes. Dermatological preparations of glucocorticosteroids are no longer prohibited, and intravenous infusions will be a prohibited method in 2005, except as a legitimate acute medical treatment. In cases of violations of anti-doping regulations where it is permissible for the affected person to furnish proof of exoneration, the burden of proof is not higher than that required to prove the violation. The sanctions provided for in the World Anti-Doping Code follow a principle of rules and exceptions which at first glance seems difficult to understand. In the case of doping violations by physicians, the anti-doping code provides--as a general rule--for exclusion from sports associations for at least four years. Since several of the changes are questionable under constitutional aspects, it remains to be seen whether the World Anti-Doping Code 2003 will allow the achievement of a universal standard to combat doping.

Adrenergic beta-Agonists↗

Laminin-5 gamma 2 chain expression in cervical intraepithelial neoplasia and invasive cervical carcinoma.

BACKGROUND: To analyze the expression of laminin-5 gamma 2 chain, a protein which plays a major role in keratinocyte migration, in cervical intraepithelial neoplasia (CIN), and invasive cervical carcinoma associated with high-risk oncogenic human papillomaviruses (HR-HPVs). MATERIAL AND METHODS: The expression of laminin-5 gamma 2 chain protein has been analyzed by immunohistochemistry in 17 cases of low-grade squamous intraepithelial lesions (LSIL-CIN1), 35 high-grade squamous intraepithelial lesions (HSIL-CIN2/3), 18 microinvasive or invasive carcinomas, and three metastatic lymph nodes. All these lesions have been proved to contain HR-HPVs and were also positive for p16 protein which classically is overexpressed at all stages of cervical neoplasia and dysplasia linked with HR-HPVs. 20 cases of normal cervix served as controls. RESULTS: The expression of laminin-5 gamma 2 chain protein was observed in 100% of invasive or microinvasive carcinoma and in their related lymph node metastasis with an immunoreactivity located preferentially at the invasive front of the lesions. All the HSILs (100%) associated with invasive carcinoma were also positive. In contrast, in HSILs without associated invasive component, the expression of the protein has been found in only 34% of cases. In positive HSILs, laminin-5 gamma 2 protein was expressed in basal layers. In LSILs and normal epithelium, no expression of the protein was noted. CONCLUSIONS: We conclude the following: (i) the expression of laminin-5 gamma 2 is a late event in cervical carcinogenesis increasing with the grade of dysplastic lesions; (ii) laminin-5 gamma 2 expression facilitates the identification of invasive and microinvasive lesions which could be difficult to diagnose on the basis of routine stains; (iii) laminin-5 gamma 2 expression in HSILs could potentially identify those lesions with a more increased risk of tumor progression.

Biomarkers, Tumor↗

A new family with frontotemporal dementia with intronic 10+3 splice site mutation in the tau gene: neuropathology and molecular effects.

Mutations in the tau gene cause familial frontotemporal dementia with parkinsonism linked to chromosome 17 characterized by filamentous tau protein deposits. Here we describe the clinical and neuropathological features of a case from a newly identified family with an intron 10+3-splice site mutation in the tau gene. The proband presented with severe personality changes and stereotyped speech followed by parkinsonian symptoms. He died at age 56 after a disease duration of approximately 6 years. At autopsy, there was marked frontotemporal degeneration with abundant tau-immunoreactive neuronal and glial inclusions widespread in the cortex and brainstem. RT-PCR analysis revealed a 3.7-fold increase of tau transcripts with exon 10, resulting in an 1.7-fold higher expression level of 4-repeat tau isoforms in soluble tau fractions when compared to control brains and exclusively 4-repeat tau isoforms in the sarcosyl-insoluble tau fractions. In accordance with the hypothesis that the overexpression leads to saturation of microtubule binding sites and an increase of unbound 4-repeat tau isoforms which assemble into filaments, the neuronal and glial inclusions in this case were exclusively composed of 4-repeat tau isoforms. The clinical and neuropathological data of this family are compared with results from the two other published families with the intron 10 + 3 mutation, the MSTD and the SOT 254 family.

Base Sequence↗

Electron holography of non-stained bacterial surface layer proteins.

We report transmission electron microscopy (TEM) investigations on bacterial surface layers (S-layers) which belong to the simplest biomembranes existing in nature. S-layers are regular 2D protein crystals composed of single protein or glycoprotein species. In their native form, S-layers are weak phase objects giving only poor contrast in conventional TEM. Therefore, they are usually examined negatively stained. However, staining with heavy metal compounds may cause the formation of structural artefacts. In this work, electron microscopy studies of non-stained S-layers of Bacillus sphaericus NCTC 9602 were performed. Compared to other proteins, these S-layers are found relatively stable against radiation damage. Electron holography was applied where information about phase and amplitude of the diffracted electron wave is simultaneously obtained. In spite of small phase shifts observed, the phase image reconstructed from the hologram of the non-stained S-layer is found to be sensitive to rather slight structure and thickness variations. The lateral resolution, obtained so far, is less than that of conventional electron microscopy of negatively stained S-layers. It corresponds to the main lattice planes of 12.4 nm observed in the reconstructed electron phase image. In addition, as a unique feature of electron holography the phase image provides thickness information. Thus, the existence of double layers of the protein crystals could be easily visualized by the height profile of the specimen.

Bacillus↗

[Exercise-induced acute bilateral isolated anterolateral compartment syndrome of the leg: a case report of a rare condition].

Acute compartment syndrome of the leg is generally a consequence of trauma. Exercise-induced acute compartment syndrome of the leg is an exceptional clinical entity observed in the context of a chronic compartment syndrome or as an isolated acute syndrome subsequent to an intense effort. Our patient was a young athlete with no history of exercise-induced leg pain. Following a soccer game, he developed an acute leg syndrome involving the anterolateral compartment of both legs. The diagnosis was not suggested by the patient's history (no notion of chronic compartment syndrome) nor the natural history of the condition but was retained on the basis of the clinical presentation and course then confirmed by intramuscular pressure measurements. Emergency treatment by fasciotomy under general anesthesia in the operating room led to cure with no sequela. The fasciotomy was closed on day 9 with simple skin sutures. Surgeons should be aware that acute exercise-induced compartment syndrome (with the risk of severe functional consequences) may be the cause of unexplained intense leg pain. The diagnosis is established on the basis of clinical findings and measurement of intramuscular pressures. Pain is the cardinal sign, sometimes associated with sensorial deficit. The compartment is hard and painful at palpation. Passive stretching exacerbates the pain. Compartment pressure is required for certain diagnosis, most Authors accepting > 30mmHg as a positive test. Emergency fasciotomy is required.

Acute Disease↗

[Recessive dystrophic epidermolysis bullosa (Hallopeau-Siemens) with IgA nephropathy: 4 cases].

BACKGROUND: The Hallopeau-Siemens type of recessive dystrophic epidermolysis bullosa (HS-RDEB) is a severe hereditary dermatosis, associated with a collagen VII deficiency. A chronic inflammatory syndrome, secondary to recurrent cutaneous infections, may be the cause of AA amyloidosis, with chronic renal failure, involving life prognosis. Less frequently, an IgA glomerulonephritis may occur and induce renal failure. Only two cases have been previously described. We report herein four new cases. CASE REPORT: We report four cases of HS-RDEB associated with IgA glomerulonephritis. A renal biopsy confirmed the diagnosis in all four cases. Later on, two patients had a second renal biopsy, indicated for deterioration of renal function. One of these patients showed AA type renal amyloidosis on the second biopsy. None of these six biopsies, conducted in our four patients led to local cutaneous complications. Subsequently three patients presented with terminal renal failure. Hemodialysis was set up, with good tolerance and improvement in quality of life. DISCUSSION: IgA glomerulonephritis should be suspected if a patient with HS-RDEB presents with hematuria. Renal biopsy is not contraindicated, confirms the diagnosis and helps to specify the prognosis. Hemodialysis is possible and well tolerated in the terminal stage of renal failure. There is not enough evidence for a genetic link between HS-RDEB and IgA glomerulonephritis, but repeated skin infections may be involved in the pathophysiology of the renal disease.

Adult↗

Phosphoserine--a convenient compound for modification of calcium phosphate bone cement collagen composites.

Temporary bone replacement materials on the basis of calcium phosphates and hydroxyapatite (HAP) are used in surgery for filling bone defects. Components which are able to control the nucleation and crystal growth of HAP through their functional groups and which can additionally activate bone cells may be helpful in the development of materials with enhanced remodelling in vivo. In this study, the influence of O-phospho-L-serine (PS) on the materials properties of calcium phosphate bone cement composites was investigated. For up to an addition of 25 mg/g PS a strong increase in the stability of the cements under load was determined. The material was studied by scanning electron microscopy and transmission electron microscopy. A more dense microstructure and a plate-like morphology of the HAP-crystals were detected in the modified composites compared with the non-modified samples. By X-ray powder diffraction an inhibition of the dissolution of alpha-tricalcium phosphate (alpha-TCP) and dicalciumphosphate anhydrous (DCPA) particles was found. alpha-TCP and DCPA are the main constituents of the cement precursor. The results of cell culture studies using rat calvaria osteoblasts demonstrate a good viability of the cells on the PS-modified material. Furthermore, the proliferation and differentiation were found to be enhanced on the PS-modified material.

Animals↗

WT1 gene mutation responsible for male sex reversal and renal failure: the Frasier syndrome.

We report the case of a young woman with primary amenorrhea. In her childhood, she suffered from renal failure requesting kidney transplantation at the age of 11. The investigations for primary amenorrhea revealed a hypergonadotropic hypogonadism associated with 46 XY karyotype. The association of primary amenorrhea with renal failure suggested Frasier syndrome (FS) or Denys-Drash syndrome (DDS). Genetic analysis revealed a Wilms' tumour (WT1) gene mutation characteristic of the Frasier syndrome. Dysgenetic ovaries were removed laparoscopically due to the risk of gonadal cancer.

Adult↗

Early failure of the tissue engineered porcine heart valve SYNERGRAFT in pediatric patients.

OBJECTIVES: The first tissue engineered decellularized porcine heart valve, Synergraft (Cryolife Inc., USA) was introduced in Europe as an alternative to conventional biological valves. This is the first report of the rapid failure of these new grafts in a small series. MATERIALS AND METHODS: In 2001, 2 model 500 and 2 model 700 Synergraft valves were implanted in four male children (age 2.5-11 years) in the right ventricular outflow tract as a root. Two patients had a Ross operation and two had a homograft replacement. RESULTS: The cryopreserved Synergraft valves appeared macroscopically unremarkable at implantation. Recovery from surgery was uneventful and good valve function was demonstrated postoperatively. Three children died, two suddenly with severely degenerated Synergraft valves 6 weeks and 1 year after implantation. The third child died on the 7th day due to Synergraft rupture. Subsequently the fourth graft was explanted prophylactically 2 days after implantation. Macroscopically all four grafts showed severe inflammation starting on the outside (day 2 explant) leading to structural failure (day 7 explant) and severe degeneration of the leaflets and wall (6 weeks and 1 year explant). Histology demonstrated severe foreign body type reaction dominated by neutrophil granulocytes and macrophages in the early explants and a lymphocytic reaction at 1 year. In addition significant calcific deposits were demonstrated at all stages. Surprisingly pre-implant samples of the Synergraft revealed incomplete decellularization and calcific deposits. No cell repopulation of the porcine matrix occurred. CONCLUSION: The xenogenic collagen matrix of the Synergraft valve elicits a strong inflammatory response in humans which is non-specific early on and is followed by a lymphocyte response. Structural failure or rapid degeneration of the graft occurred within 1 year. Calcific deposits before implantation and incomplete decellularization may indicate manufacturing problems. The porcine Synergraft treated heart valves should not be implanted at this stage and has been stopped.

Animals↗

Comparison of different decellularization procedures of porcine heart valves.

BACKGROUND: Tissue engineering of heart valves should avoid the disadvantages of conventional prostheses. In this study we tested different decellularization procedures for their potential of cell removal and their ability to preserve the matrix. METHODS: Specimens of porcine aortic and pulmonary roots were treated with either trypsin or sodium-dodecyl-sulfate (SDS) or Triton-X 100 and sodium-deoxycholate with a range of concentrations. Tissue samples were then processed for scanning electron microscopy and laser scanning microscopy. RESULTS: Trypsin achieved only incomplete decellularization and caused severe structural alterations of the matrix. In contrast SDS removed cells completely but caused strong structural alterations. Treatment with Triton-X100 and sodium-deoxycholate achieved both complete decellularization and preservation of the matrix structure. CONCLUSION: Techniques of decellularization are highly variable in efficiency and matrix preservation and was best achieved in our study with Triton-X100 and sodium deoxycholate.

Animals↗

[Coverage of heel tissue loss by two pediculated flaps in a single procedure].

We report the case of a traffic accident victim who suffered major tissue loss of the heal. We used two pediculated flaps to close the gap in a single procedure. The remaining tissue presented zones of necrosis from the plantar aspect to the posterior half of the calcaneum, up to the insertion of the calcaneus tendon, extending 5 cm on the posterior aspect of the heal. We decided to combine a medial plantar flap with a lateral supramalleolar flap. The thick medial plantar flap allowed cover of the calcaneum and sensitivity. The calcaneus tendon was covered with the lateral supramalleolar flap. The thickness of the flap was adapted to match the tissue defect. At six months, the patient had recovered walking function with satisfactory weight bearing on the heal. Flap sensitivity was satisfactory with no slipping phenomenon.

Accidents, Traffic↗

[Epiphyseal tibial osteoblastoma: report of a rare localization and review of the literature].

Osteoblastoma is an uncommon benign bone tumor diagnosed in about 1% of primary bone tumors. Predominantly observed in the axial skeleton, it can be observed in long bones (20%), generally in the diaphysis (80% of the long bone localizations). In typical cases, standard imaging is highly suggestive of the diagnosis. The typical image is a "lytic" zone surrounded by bony condensation, and a minimal osteosclerotic reaction peripherally, rarely invading the soft tissues. Diagnosis is confirmed at pathology: osteoblast-like cells disseminated in an abundant conjunctive background surrounded by immature richly vascularized bone. The tumor we report presented an unusual localization and an atypical aspect on the imaging studies. Located in the tibial epiphysis, this osteoblastoma invaded the soft tissues, as seen on the CT and MRI studies which visualized an encapsulated tumor with a calcified shell and a liquid-like tumefaction suggestive of a tumor arising from the synovial.

Adult↗

[Arthroscopy-guided treatment of fractures of the distal radius: 16 wrists].

PURPOSE OF THE STUDY: We report our experience with arthroscopy-guided treatment of fractures of the distal radius. MATERIAL AND METHODS: Between November 2001 and June 2002, 16 patients (10 men, 6 women, mean age 51 years, age range 24-75 years) underwent arthroscopy-guided treatment of articular fractures of the distal radius. Patients were installed with the arm held in a horizontal position with a brace, the wrist under traction. The same procedure was used in all cases: introduction of the arthroscope, joint cleaning and shaving, search for lesions, arthroscopy-guided treatment. Kirschner 2-mm pins were used for fixation in all cases, combined with 1.2-mm pins in the event of ligament injury. RESULTS: Arthroscopic exploration revealed cartilage impaction in 25% of the wrists and ligament injuries in 30%. One fixation disassembled and was not remounted. There were two cases of reflex dystrophy. There were no arthroscopy-related complications. Bone healing was achieved in eight weeks in all cases. The mean DASH score was 22.5 at six months follow-up (range 3-10). DISCUSSION CONCLUSION: Arthroscopy-guided treatment of fractures of the distal radius was attempted for the first time in the early 90s. Per-operative arthroscopy enables a good view of the fracture and associated lesions (cartilage impaction, scapholunate, lunotriquetral ligament injury) and facilitates control of the reduction. Arthroscopy is technically simple and is the technique of choice due to the lack of morbidity. Several authors have reported their experience in more or less extensive series. Two notions should be emphasized. First, defective intra-articular reduction greater than 1 mm may lead to osteoarthritis of the wrist in 90% of the cases. Secondly, intra-operative imaging (fluoroscopy) does not provide sufficient precision to visualize a 1-mm stairstep in the articular surface, raising the risk of radiocarpal degeneration at mid term despite often satisfactory postoperative x-rays. We thus propose intra-operative arthroscopy to control the treatment of all articular wrist fractures, with or without displacement, in order to ensure satisfactory reduction with less than 1-mm defect in the articular surface and to search for and treat any associated bone or ligament injuries not diagnosed before surgery.

Adult↗

[Treatment of urinary incontinence in women and the role of physiotherapy].

Physiotherapy including pelvic floor muscle exercises, vaginal cones, biofeedback or electrical stimulation can be recommended as first step therapy for genuine stress incontinence. However physiotherapy has its limitations: 30% of women do not improve at all and only 10 to 20% of women are totally dry after treatment. In case of failure or insufficient response, surgery must be considered. Until recently, the gold standard for the treatment of urinary incontinence was the "Burch" procedure. However the surgical approach has been considerably modified since the introduction by Ulmsten in 1995 of the tension-free vaginal tape (TVT) and more recently of the "Uratape". Short and mid-term results of the TVT are very encouraging with about 85% "dry patients" at five years follow-up. This technique can also be used with good results in patients with a low urethral pressure (< 20 cm H2O). Of course the superiority of TVT over other "classical techniques" must be confirmed by randomized comparative studies.

Equipment Design↗