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Biomedical subjects

P Massin

Publications and source records attributed to P Massin.

At least 19 recordsLinked to original sources

Placental growth factor-1 and epithelial haemato-retinal barrier breakdown: potential implication in the pathogenesis of diabetic retinopathy.

AIMS/HYPOTHESIS: Disruption of the retinal pigment epithelial (RPE) barrier contributes to sub-retinal fluid and retinal oedema as observed in diabetic retinopathy. High placental growth factor (PLGF) vitreous levels have been found in diabetic patients. This work aimed to elucidate the influence of PLGF-1 on a human RPE cell line (ARPE-19) barrier in vitro and on normal rat eyes in vivo. METHODS: ARPE-19 permeability was measured using transepithelial resistance and inulin flux under stimulation of PLGF-1, vascular endothelial growth factor (VEGF)-E and VEGF 165. Using RT-PCR, we evaluated the effect of hypoxic conditions or insulin on transepithelial resistance and on PLGF-1 and VEGF receptors. The involvement of mitogen-activated protein kinase (MEK, also known as MAPK)/extracellular signal-regulated kinase (ERK, also known as EPHB2) signalling pathways under PLGF-1 stimulation was evaluated by western blot analysis and specific inhibitors. The effect of PLGF-1 on the external haemato-retinal barrier was evaluated after intravitreous injection of PLGF-1 in the rat eye; evaluation was by semi-thin analysis and zonula occludens-1 immunolocalisation on flat-mounted RPE. RESULTS: In vitro, PLGF-1 induced a reversible decrease of transepithelial resistance and enhanced tritiated inulin flux. These effects were specifically abolished by an antisense oligonucleotide directed at VEGF receptor 1. Exposure of ARPE-19 cells to hypoxic conditions or to insulin induced an upregulation of PLGF-1 expression along with increased transcellular permeability. The PLGF-1-induced RPE cell permeability involved the MEK signalling pathway. Injection of PLGF-1 in the rat eye vitreous induced an opening of the RPE tight junctions with subsequent sub-retinal fluid accumulation, retinal oedema and cytoplasm translocation of junction proteins. CONCLUSIONS/INTERPRETATION: Our results indicate that PLGF-1 may be a potential regulation target for the control of diabetic retinal and macular oedema.

Cell Culture Techniques↗

Comparative effects of five bisphosphonates on apoptosis of macrophage cells in vitro.

Bisphosphonates (BPs) inhibits bone resorption by reducing osteoclastic activity; they induce osteoclast apoptosis. Pathophysiology of prostheses loosening is complex and implies an inflammatory reaction secondary to the phagocytosis of wear debris by macrophages with a secondary increased bone resorption by osteoclasts. BPs inhibit proliferation and cause cell death in macrophages by induction of apoptosis. We have used mouse macrophage-like J774.1 cells to evaluate the effects of five BPs. J774A.1 cells were cultured in a standard culture medium for 2-days. BPs (alendronate, pamidronate, etidronate, risedronate, zoledronic acid) were added in the medium at concentration of 10(-6) to 10(-4)M during 3 days. Cells were studied by fluorescence microscopy after staining with the fluorescent dye Hoescht H33342 and the percentage of apoptotic cells was determined on 300 nuclei. Cells were analyzed by flow cytofluorometry after staining with annexin V-FITC (for counting apoptotic cells) and propidium iodide (for necrotic/late-apoptotic cells) on 2000 cells. Etidronate did not cause significant apoptosis or necrosis, at any concentration. Alendronate and pamidronate caused apoptosis and death only at very high concentration [10(-4)M]. On the contrary, apoptotic and necrotic cells were evidenced with risedronate or zoledronic acid at lower concentrations. These effects were dose-dependant and occurred when concentration reached [10(-5)M]. The number of apoptotic cells was higher with zoledronic acid and then with risedronate. Cytofluorometry appeared superior to cytologic analysis in the investigation of macrophage apoptosis, since necrotic cells loose contact with the glass slides and are not identifiable in cytological counts. Some amino-BPs appear to induce apoptosis in macrophages.

Animals↗

Relationship between macular hole size and the potential benefit of internal limiting membrane peeling.

AIM: To investigate the relationship between the size of macular holes and the possible benefit of internal limiting membrane (ILM) peeling. METHODS: 84 consecutive cases of idiopathic macular hole followed up for at least 3 months were included in this retrospective study. Surgery comprised pars plana vitrectomy, peeling of any epiretinal membrane, 17% C2F6 (hexafluoroethane) gas filling and 10 days of positioning. 36 eyes had ILM peeling. The main outcome measure was the macular hole closure rate checked by optical coherence tomography. RESULTS: The overall postoperative closure rate was 90.5%. For macular holes > or =400 microm in diameter, the rate was 100% with ILM peeling versus 73.3% without (p = 0.015). For smaller macular holes, the rates were 100% in both groups. Postoperative gain in visual acuity was not significantly different in eyes with ILM peeling and those without. CONCLUSIONS: ILM peeling does not seem to be useful for macular hole <400 mum in diameter. Its likely benefit has to be investigated for larger macular hole sizes, for which the failure rate is higher.

Aged↗

Evaluation of the effect of JPEG and JPEG2000 image compression on the detection of diabetic retinopathy.

AIMS: To compare the effect of classic Joint Photographic Experts Group (JPEG) and JPEG2000 compression algorithms on detection of diabetic retinopathy (DR) lesions. METHODS: In total, 45 colour fundus photographs obtained with a digital nonmydriatic fundus camera were saved in uncompressed Tagged Interchanged Files Format (TIFF) format (1.26 MB). They were graded jointly by two retinal specialists at a 1 month interval for soft exudates, hard exudates, macular oedema, newvessels, intraretinal microvascular abnormalities (IRMA), and retinal haemorrhages and/or microaneurysms. They were compressed to 118, 58, 41, and 27 KB by both algorithms and 24 KB by classic JPEG, placed in random order and graded again jointly by the two retina specialists. Subjective image quality was graded, and sensitivity, specificity, positive and negative predictive values, and kappa statistic were calculated for all lesions at all compression ratios. RESULTS: Compression to 118 KB showed no effect on image quality and kappa values were high (0.94-1). Image degradation became important at 27 KB for both algorithms. At high compression levels, IRMA and HMA detection were most affected with JPEG2000 performing slightly better than classic JPEG. CONCLUSION: Performance of classic JPEG and JPEG2000 algorithms is equivalent when compressing digital images of DR lesions from 1.26 MB to 118 KB and 58 KB. Higher compression ratios show slightly better results with JPEG2000 compression, but may be insufficient for screening purposes.

Algorithms↗

[Retrograde locked nailing of humeral shaft fractures: a prospective study of 58 cases].

PURPOSE OF THE STUDY: Appropriate treatment for humeral shaft fractures remains a debated issue. Among the classical osteosynthesis techniques proposed, closed nailing was adapted to the humerus rather late, using the anterograde method. Use of retrograde nailing, which spares the rotator cuff, is more recent. The purpose of this study was to report outcome in 58 humeral shaft fractures in adults treated using the universal humeral nail between January 2000 and December 2003. MATERIAL AND METHODS: This work was limited to recent shaft fractures in adults with non-pathological bones. The fractures included were all situated between the insertion of the pectoralis major and a point situated 2 cm above the apex of the olecraneum fossa. The series included 58 patients with 58 humeral shaft fractures. All fractures were closed except four (Gustilo type I and II). Two patients presented preoperative radial paralysis which was not considered to be a contraindication for retrograde locking nailing. The paralysis recovered in both patients, after neurolysis performed during the nailing procedure in one. Osteosynthesis was performed without opening the fracture focus under fluoroscopic control using a static locking nail inserted retrograde in patients in the supine position. RESULTS: There were two early deaths unrelated to the method. Healing was obtained in the surviving patients within fifteen weeks on average. Bone healing was primary in 53 patients and after secondary compression in three. At last follow-up, shoulder motion was normal in 88% of patients and elbow motion in 91%. The Rommens functional score was good in 84%. Complications included three cases of spontaneously regressive postoperative radial paralysis, three cases of reflex dystrophy including two which regressed, and two cases of humeral palette fracture requiring surgical osteosynthesis. The proximal screws were removed in six patients because of pain or migration. To date, implants have been removed in three patients without problem. There were no infections. CONCLUSION: Retrograde insertion of this nail facilitates treatment of humeral shaft fractures by allowing immediate joint motion and the advantages of closed reduction: no infection, no late bone healing requiring conversion to another method of fixation. The residual technical problems concern proximal nailing and nail introduction.

Adolescent↗

Kearns Sayre syndrome: an unusual form of mitochondrial diabetes.

Kearns Sayre syndrome (KSS) is a mitochondrial disorder characterized by the emergence before age 20 of progressive external ophthalmoplegia, pigmentary retinopathy, together with other heterogeneous clinical manifestations, including cardiac conduction defects, muscle abnormalities and endocrinopathies. KSS is associated with large heteroplasmic deletions in mitochondrial DNA. We report the case of a 43-year-old woman, with diabetes mellitus as a first manifestation at age 19. Later, she exhibited bilateral ptosis and external ophthalmoplegia with progressive worsening. DNA analysis identified a large mitochondrial DNA (mtDNA) deletion, which confirmed the diagnosis of KSS. By reporting this case with diabetes mellitus as first manifestation, we aim at emphasizing problems of diagnosis in these subtypes of mitochondrial diabetes.

Biopsy↗

[Measurement of head penetration on digitalized radiographs: reproducibility and accuracy].

PURPOSE OF THE STUDY: Wear of the acetabular component of total hip arthroplasty (THA) is incriminated as the cause of loosening and bone resorption. Consequently, an accurate evaluation of wear can contribute to the prediction of mechanical failure of the arthroplasty. Among the different methods proposed, digitalized imaging using a high-resolution scanner associated with data processing procedures appears to be a simple easily accessible technique. A system based on this concept has been introduced in orthopedics. To our knowledge, there has been no report on the system's reproducibility and accuracy. MATERIAL AND METHODS: Thirty-nine radiography series for THA served as the basis for the evaluation of intra- and interobserver reproducibility. We evaluated the error induced by digitalization, the error induced by digitalized measurement, the accuracy of the measurements as a function of the material constituting the bearing, the intra- and interobserver reproducibility for repeated measures of THA wear (six observers and two observations). All measurements were done after digitalization and analyzed with a specimen designed software. RESULTS: The inter and intra-observer coefficients of concordance were 0.6 and 0.58 respectively, i.e. moderate reproducibility. Depending on the prosthetic material, the error and accuracy of the system varied from 0.112 to 0.44 mm and 0.28 to 1.29 mm respectively. To obtain valid inter-observer reproducibility, the number of observers had to be limited to three (coefficient = 0.82). The type of implant had an influence on measurement error. The error was 0.342 for polyethylene cups and 0.118 for press-fit metal back cups. Likewise, for a metallic head measuring 22.2 mm, the error was 0.138 mm while for a ceramic head or metal head measuring 28 mm, the error was 0.28 mm and 0.112 mm respectively. DISCUSSION AND CONCLUSION: The accuracy and error depend directly on the type of implant. The accuracy was better for metallic heads associated with metal-backed cups. To obtain satisfactory interclass correlation, the number of observers should be three. The proposed digitalized measurement system should be relatively accurate and reproducible. Its use can be recommended for the evaluation of wear after five years of follow-up, limiting the number of observers to three.

Acetabulum↗

[Advantages of acetazolamide associated with anti-inflammatory medications in postoperative treatment of macular edema].

PURPOSE: To analyze the effectiveness of acetazolamide associated with topical nonsteroidal anti-inflammatory drugs (NSAIDs) and/or steroids in the treatment of postsurgical macular edema (ME). PATIENTS AND METHODS: Sixteen eyes of 15 consecutive patients presenting with clinical ME 1-120 months after ophthalmologic surgery were studied retrospectively. The mean duration of ME before treatment was 5 months. All patients were treated with 250-500 mg of acetazolamide per day, associated with topical NSAIDs and/or steroids for an average of 6.9 months. The main outcome measures were the best-corrected visual acuity expressed in Log MAR, and the retinal thickness evaluated with OCT. RESULTS: The mean initial visual acuity was 20/100 (0.7 +/- 0.28 Log MAR), with a macular thickness of 599.67 +/-174.17 microm (average +/- standard deviation). The mean final visual acuity was 20/40 (+0.3 +/- 0.2 Log MAR) with a macular thickness of 264.69 +/- 106.59 microm. Treatment was effective in 87.5% of overall cases. The effectiveness was 100% in the subgroup treated with acetazolamide, NSAIDs, and steroids. CONCLUSION: This study suggests that medical treatment with a combination of acetazolamide, topical NSAIDs and/or steroids may be beneficial for reducing retinal thickness and improving vision in postsurgical ME.

Acetazolamide↗

[Diabetes and mitochondrial cytopathies: pathological studies].

Maternal diabetes associated with neural deafness is designated as MIDD (maternal inherited diabetes and deafness); it is linked to a A3243G tRNA leucine gene mutation. The disease course is progressive and involvement of other systems is frequent. In most cases, macular pattern dystrophy is present. Muscular lesions are characteristic of mitochondrial myopathies. Mitochondrial abnormalities have also been observed in pancreas, heart, kidney, smooth muscle of the digestive tract with variable heteroplasmy levels. MIDD may present as a single syndrome or is part of MELAS or Kearns-Sayre syndrome.

Deafness↗

Evaluation of a screening program for diabetic retinopathy in a primary care setting Dodia (Dépistage ophtalmologique du diabète) study.

OBJECTIVES: The aim of this observational study was to evaluate the screening for diabetic retinopathy (DR) using eye fundus photography taken by a nonmydriatic camera and transmitted trough the Internet to an ophthalmological reading centre, as compared to a dilated eye examination performed by an ophthalmologist. METHODS: A total of 456 and 426 diabetic patients were included by two different groups of primary care physicians (PCPs), 358 being screened with the non-mydriatic camera (experimental group) and 320 with dilated eye fundus exam (control group). RESULTS: The proportion of screened patients for whom PCPs received a screening report within the 6-month follow-up period was 74,1% for the experimental group and 71,5% for the control group. Screening for DR was negative in 77,6% of patients with eye fundus photographs vs 89,6% with dilated eye examination. DR was diagnosed in 62 patients (17,3%) with eye fundus photographs versus 31 with dilated eye examination (10,4%). Referral to an ophthalmologist was required in 59 reports of patients with photographs (16.5%), 23 of them due to high grade DR. Finally, the non-mydriatic camera was found of little inconvenience by patients. CONCLUSION: The telemedical approach to DR screening proved to be effective in providing primary care practitioners with information about their patient's eye status. This screening method allowed to identify patients requiring prompt referral to the ophthalmologist for further complete eye examination. In conclusion, this study provided successful results of DR screening using fundus photography in primary care patients, and strongly supports the need to further extend this screening program in a larger number of French sites.

Diabetes Mellitus, Type 1↗

Comparison of optical coherence tomography models OCT1 and Stratus OCT for macular retinal thickness measurement.

AIMS: To compare the values measured for retinal macular thickness with the first and last generations of the optical coherence tomograph (OCT1 and Stratus OCT, Zeiss, Humphrey Division). METHODS: This was a cohort study. 59 eyes were examined: 17 had a normal macula and 42 had a diabetic macular oedema. In each eye, mean retinal thickness (RT) was measured automatically in the nine macular Early Treatment Diabetic Retinopathy Study areas and at the foveal centre, using OCT1 and Stratus OCT. The paired mean RT values for each area and the type and proportion of artefacts were compared. RESULTS: Of the 590 automatic measurements, 505 had no artefact, either with OCT1 or Stratus OCT. The mean difference between the OCT1 and Stratus OCT measurements was 25 (SD 26.2) microm (p<0.0001). With Stratus OCT, RT values were significantly higher, by 8.1% (7.8%), than with OCT1. Artefacts were only observed in cases of diabetic macular oedema and were significantly more frequent with OCT1 than Stratus OCT (10.5% versus 4.4, p<0.0001). CONCLUSION: The macular retinal thickness values measured with Stratus OCT were significantly higher than those measured with OCT1. Stratus OCT has the advantage of producing fewer artefacts than OCT1 in pathological cases.

Adult↗

Advanced glycation end products can induce glial reaction and neuronal degeneration in retinal explants.

BACKGROUND/AIMS: Neuronal degeneration has been reported to occur in diabetic retinopathy before the onset of detectable microvascular abnormalities. To investigate whether advanced glycation end products (AGE) could be directly responsible for retinal neurodegeneration, retinal explants were incubated with glycated bovine serum albumin (BSA). METHODS: Retinal explants obtained from non-diabetic adult rats were incubated 4 days with or without 200 mug/ml glycated BSA. Neural apoptosis was quantified by terminal dUTP nick end labelling (TUNEL) binding and immunostaining with anti-cleaved caspase-3 antibody. Expression of glial fibrillary acidic protein (GFAP) was localised by immunofluorescence. RESULTS: TUNEL and cleaved caspase-3 positive cells increased significantly by 2.2-fold and 2.5-fold in retinal explants incubated in glycated BSA (p<0.05), respectively. The ganglion cell layer was the most sensitive retinal layer to the glycated BSA. Neuronal degeneration was confirmed by the increased GFAP labelling in Müller glial cells from retinal explants treated with glycated BSA. CONCLUSION: These results suggest that AGE could induce retinal neurodegeneration in the absence of blood perfusion. Cells in the ganglion cell layer appeared to be the most sensitive as in diabetic retinopathy and its animal models. AGE toxicity could therefore contribute to the early pathological mechanisms of diabetic retinopathy.

Animals↗

Migration of polyethylene debris along well-fixed cemented implants.

Implants, consisting of smooth Inox cylinders, were cemented into the lower femur and upper tibia of nine sheep to study the distal migration of polyethylene particles. Some implants had a titanium-bead porous coat at the proximal end. These were of three types: In the first type, the porous coat was covered with hydroxyapatite to obtain a bony seal; the second type was prepared for a polymethylmethacrylate seal; in the third type, the porous zone was surrounded by a 2-mm-thick space to allow the formation of a fibrous seal. Small polyethylene particles were injected into the knees once a week during the third and fourth months after implantation. The animals were euthanized 2 months later. Major longitudinal sections of the implants and the surrounding bone were examined under a polarized light microscope. Birefringent particles were counted at the cement-bone and cement-implant interfaces. Osteolysis was not observed. None of the seals significantly decreased the migration of particles around the cemented part of the implants. Particles were observed in cement fissures and vacuoles. They migrated at both interfaces and in the bone itself. They were visible in marrow spaces between bone trabeculae.

Animals↗

[The "vessel case flap". About one case in the lower limb].

The authors report an atypical case of lower limb repair in a 69-year-old patient, who presented a closed fracture of the tibia initially fastened with a plate. Skin necrosis developed after osteosynthesis, exposing the plate and the fracture bone. Because of the vascular state of the patient (smoking, arteritis, diabetes), any microsurgical procedure seemed likely to fail. The incisions previously performed contraindicated any form of pedicle flap in the leg area. An original solution was then proposed, involving the long extensor muscle of the great toe pedicled proximally on the anterior tibial artery. After six months of follow-up, healing and bone consolidation have been achieved. The interest of this exceptional technique is considered with respect to therapeutic choices for lower limb repair.

Aged↗

Screening for diabetic retinopathy in France.

Ocular complications of diabetes, particularly retinopathy, are the major cause of blindness in the working age population in industrialised nations. Laser photocoagulation has shown definite results in reducing visual morbidity with many more likely to benefit if diagnosed early enough. Institution of an efficient screening programme aimed at detecting patients at risk when they can still be effectively treated has been recognised as an urgent priority worldwide. In France, a signatory to the Saint Vincent's Declaration, an analysis of the national healthcare database reveals a gross inadequacy in the current extent of screening for diabetic retinopathy. The possible causative factors have been analysed and the necessary corrective measures, some of which are already under way, have been discussed. Ideally, screening by ophthalmologists at recommended intervals have been advised by national and professional health care associations. This has not been feasible owing to the lack of organised planning and serious manpower deficit caused by a progressive decline in the number of ophthalmologists. Recently, the need for an efficient, widely-available and user-friendly screening tool has led to the evaluation of multifield fundus photography in real time using digital nonmydriatic camera in comparison with more established methods of detecting diabetic retinopathy. Lastly, the future possibility of involving in France non-ophthalmologists like endocrinologists or general practitioner or non medical profession like orthoptists after proper training to meet the necessary manpower shortage has been addressed. Optimal use of telemedicine along with establishment of preferential reference channels for newly discovered cases of sight-threatening cases of retinopathy are public health priority necessary to give to the screening of diabetic retinopathy its full efficiency.

Diabetic Retinopathy↗

Heterogeneity of diabetes phenotype in patients with 3243 bp mutation of mitochondrial DNA (Maternally Inherited Diabetes and Deafness or MIDD).

OBJECTIVE: In patients with maternally inherited diabetes and deafness (MIDD), due to 3 243 A > G mutation of mitochondrial DNA (mtDNA), diabetes may present with variable phenotypes. OBJECTIVE: To ascertain the existence of two distinct phenotypes, MIDD1 and MIDD2, in a series of patients with MIDD. DESIGN: Multicenter prospective study. PATIENTS: 77 patients with diabetes and the mtDNA 3243 mutation and 139 control patients with type 1 (T1D) or type 2 (T2D) diabetes, matched according to initial presentation of diabetes, age at onset, sex, and duration of diabetes (24 T1D and 115 T2D, including 55 treated with insulin). MEASUREMENTS: Anthropometric characteristics (height, body weight, body mass index [BMI], sex), family history of diabetes, and characteristics of diabetes (age at onset, treatment, hemoglobin A1c [HbA1c]), extrapancreatic manifestations. RESULTS: In 13 cases (17%, MIDD1), diabetes presented as insulin-dependent from the onset, with ketoacidosis in 6 cases. In 64 cases (83%, MIDD2), diabetes resembled T2D, and was treated with diet in 12 cases, oral hypoglycemic agents in 21 cases, or insulin in 31 cases. Compared with patients with MIDD2, patients with MIDD1 were characterized by lower age at onset of first manifestation of MIDD (25.4 +/- 9.6 vs 33.7 +/- 13.2 Years, P<0.0005), lower body weight (49.1 +/- 7.4 vs 56.3 +/- 10.9 kg, P<0.0025), lower BMI (18.2 +/- 2.3 vs 20.9 +/- 3.6 kg/m2, P<0.0005), and higher HbA1c levels (9.5 +/- 2.0 vs 7.5 +/- 1.6%, P<0.0005). Frequency of family history of diabetes and of extrapancreatic manifestations was the same in both MIDD subtypes. No difference was found within the MIDD2 subtype when comparing patients treated with or without insulin. Compared with matched controls, patients with MIDD had a lower BMI (MIDD1/T1D 18.2 +/- 2.3 vs 24.0 +/- 3.6 kg/m2 and MIDD2/T2D 20.9 +/- 3.6 vs 30.2 +/- 5.9 kg/m2, P<0.0025). Lastly, male patients with MIDD had a shorter height than controls (MIDD1/T1D: 166.1 +/- 3.2 vs 177.3 +/- 6.6 cm and MIDD2/T2D: 168.4 +/- 7.2 vs 173.6 +/- 6.6 cm P<0.025). CONCLUSIONS: These results confirm the existence of two different phenotypes in MIDD, MIDD1 and MIDD2, which may be related to the severity of the mitochondrial disease. The role of other genetic and/or environmental factors in the variable phenotype of MIDD remains to be elucidated.

Adult↗