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Biomedical subjects

P Simon

Publications and source records attributed to P Simon.

At least 127 records · Page 7Linked to original sources
PubMed1999

Pilocarpine toxicity in retinal ganglion cells.

PURPOSE: Muscarinic agents reduce intraocular pressure by enhancing aqueous outflow, probably by stimulating ciliary muscle contraction. However, pilocarpine is a well characterized neurotoxin and is widely used to generate animal seizure models. It was therefore investigated whether pilocarpine was also toxic to retinal ganglion cells. METHODS: Dissociated whole retinal preparations were prepared from postnatal day 16 to 19 rats. Retinal ganglion cells had been previously back-labeled with a fluorescent tracer. Retinal cells were incubated with pilocarpine, lithium, and inositol derivatives, and viability of the retrogradely labeled retinal ganglion cells was assayed after 24 hours. RESULTS: Pilocarpine was toxic to retinal ganglion cells in a dose-dependent fashion. This toxicity was potentiated by lithium and blocked by epi- and myo-inositol. CONCLUSIONS: Pilocarpine is toxic to retinal ganglion cells in a mixed culture assay. This toxicity appears to depend on the inositol pathway and is similar to its mode of action in other neurons. However, 0.4 mM pilocarpine (the lowest concentration that did not affect ganglion cell survival) is roughly 1000-fold higher than the vitreal concentration and 20-fold higher than the scleral concentration that can be obtained with topical administration of 2% pilocarpine in the rabbit eye.

Animals↗
PubMed1999

[Arterial hypertension in the hemodialysis patient. A model of salt-sensitive hypertension in man].

In uremic patient treated by hemodialysis (HD), a low potassium intake and a salt load due to diet and or a high sodium concentration in dialysate are often associated to refractory hypertension. Numerous reports in general population, based on epidemiologic and demographic data, have pointed to the relationship between sodium intake and hypertension. The degree of blood pressure fall in patients who have evidence of salt-sensitivity varies directly with the severity of the hypertension, being most prominent in those with higher pressures. Recent studies have suggested that a reduction of dialysate sodium can control hypertension in maintenance haemodialysis patients. In this study, five hypertensive haemodialysis patients were assigned to a regime of lowering the dialysate sodium concentration from 142 to 135 mmol/L in combination with an attempt to lower salt intake by advising the patients to eat a NaCl-restricted diet of no more than 6-8 g/day. During the period under study, dialysis time was kept constant. A significant increase of ultrafiltrate sodium concentration was observed during the first week after lowering the dialysate sodium concentration. Post dialysis systolic and diastolic pressures showed a clear trend to fall (systolic pressure 174 +/- 18 vs 118 +/- 13 mmHg, diastolic pressure 96 +/- 7 vs 75 +/- 13 mmHg) without a change of dry weight. The reduction of the mean arterial pressure on 48 h was demonstrated with ambulatory blood pressure recording. The results of this study suggest that reducing the dialysate sodium concentration lead to a decrease in peripheral resistance. A link between sympathetic overactivity as it is found in haemodialysis patients and sodium load could be a stimulating hypothesis. It is concluded that increasing dialysate sodium in short dialysis is responsible for the high prevalence of arterial hypertension often insufficiently controlled by antihypertensive medication. In hemodialysis patients with refractory hypertension, the lowering of the dialysate sodium concentration is indicated.

Aged↗
PubMed1998

Combined methods of retrograde staining, layer-separation and viscoelastic cell stabilization to isolate retinal ganglion cells in adult rats.

The adult retinal ganglion cells (RGCs) are widely used as a model to study mechanisms of de- and regeneration within the central nervous system (CNS). All regions of the CNS including the retina have the common disadvantage of being composed of heterogeneous populations of cells, many of them like RGCs making less than 1% of the total population. This disadvantage can be circumvented by methodologies aimed at purifying specific cell types. Here we describe a method that combines retrograde labelling with fluorescent dyes and the pull-off technique. By using either of four different fluorescent dyes to retrogradely label RGCs, between 55 and 80% of pre-labelled ganglion cells could be identified with fluorescence microscopy. The pull-off procedure was supplemented by enhancing the viscosity of the collecting medium with methylhydroxypropyl-cellulose (MHPC). It appeared that 45% of all RGCs could be collected in the medium containing MHPC as compared to about 19% of RGCs which could be collected in medium devoid of cellulose. Despite the fact that morphometric measurements indicated that 60% of the cells collected fulfilled the criteria of being RGCs, the population obtained was immensely enriched and sufficed to perform a two dimensional SDS-gel electrophoresis and to determine their protein composition. The collected RGCs displayed a similar protein pattern as compared to that of the total retina, indicating that sublayers of the retina were represented in the probe. The results suggest that combined approaches of in vivo staining and ex vivo separation within suitable media enables the collection of an enriched population of cells which can be processed for biochemical analysis, and perhaps for molecular biology.

Age Factors↗
PubMed1998

Automated column-switching high-performance liquid chromatography for the determination of aflatoxin M1.

An extractionless method for determining aflatoxin M1 (AFM1), a major metabolite of aflatoxin B1 (AFB1), in human urine was developed. The biological fluid is injected directly into the chromatographic system after simple dilution and centrifugation. A pre-column, packed with a cation-exchange phase and coupled on-line to a column-switching liquid chromatography (LC) system, is used for sample pre-treatment and concentration. The analytes are non-selectively desorbed with the LC eluent and cleaned by means of a column-switching procedure. Pre-treatment and analysis were performed within 40 min. Average AFMI recovery reached 97% in the 10-100 ng/l range of urine. The detection limit of AFM1 in urine and milk was 2.5 ng/l for 1 ml of injected sample. A comparison with an immunoaffinity column clean-up and LC method was performed. The method was applied to determine AFM1 in the urine of AFB1 gavaged rats, and in the urine of both potentially exposed and supposedly unexposed workers. The method was also extended to milk.

Aflatoxin M1↗
PubMed1998

A QTL with major effect on milk yield and composition maps to bovine chromosome 14.

A whole genome scan was undertaken in a granddaughter design comprising 1158 progeny-tested bulls in order to map QTL influencing milk yield and composition. In this paper we report the identification of a locus on the centromeric end of bovine Chromosome (Chr) 14, with major effect on fat and protein percentage as well as milk yield. The genuine nature of this QTL was verified using the grand2-daughter design, that is, by tracing the segregating QTL alleles from heterozygous grandsires to their maternal grandsons and confirming the predicted QTL allele substitution effect.

Alleles↗
PubMed1998

Analysis of left ventricular function after emergency coronary artery bypass grafting for life-threatening ischaemia following primary revascularization.

OBJECTIVE: Severe ischemic injury in the first few hours following primary revascularization necessitates acute reoperation. To study the effect of emergency coronary artery bypass grafting, we followed 18 patients for up to 8 years, relating their changes of global and regional myocardial function during the acute event and after secondary revascularization to final outcome. METHODS: A total of 16 patients with coronary artery bypass grafting (CABG) and 2 PTCA were treated for coronary heart disease between 1989 and 1993 and experienced life-threatening ischemic events (94% cardiogenic shock, 39% ventricular fibrillation, 67% ischemic electrocardiograph (ECG) changes) within 2.3+/-1.6 h after primary revascularization. Reoperation was carried out 1.0+/-1.3 h after the occurrence of acute ischemia. Serial echoes were obtained during the acute event and after reoperation as well as during the follow-up period. RESULTS: Of the 18 patients, 8 are currently alive, 5 died within 30 days and 4 within the 1st year. There was one late death 5 years after surgery. Global and regional wall motion was evaluated using short axis views of transesophageal echoes taken during the acute event and after secondary revascularization, and compared with transthoracic echoes in long-term survivors up to 5 years after surgery. During the acute event left ventricular ejection fraction (LVEF) was reduced in 83% of the patients and improved significantly after reoperation (chi2 = 11.74, df= 2, P < 0.01). As to regional wall motion, 50% of the segments in non-revascularized areas remained abnormal. Regional wall motion after reoperation was significantly better in the surviving patients compared with patients dying in the post-operative course (chi2 = 6.23, df= 1, P < 0.05). The revascularization score ( > 75%) of abnormal contracting segments during the acute ischemic event was a significant determinant for long-term survival. CONCLUSION: We conclude that patient outcome is determined by the severity of regional wall motion abnormality during the acute ischemic event, the aggressiveness of the attempt to revascularize these perfusion territories and their improvement after revision. Long-term survival reflects, therefore, the extent of emergency revascularization and therefore the ability to identify ischemic perfusion territories for surgical strategy planning.

Aged↗
PubMed1998

The Family Health Project: psychosocial adjustment of children whose mothers are HIV infected.

The psychosocial adjustment of 87 inner-city African American children 6-11 years old whose mothers were HIV infected was compared with that of 149 children from a similar sociodemographic background whose mothers did not report being HIV infected. Children were not identified as being HIV infected. Mother reports, child reports, and standardized reading achievement scores were used to assess 4 domains of adjustment: externalizing problems, internalizing problems, cognitive competence, and prosocial competence. The results indicated that, on average, children from both groups had elevated levels of behavior problem scores and low reading achievement scores when compared with national averages. Relative to children whose mothers were not infected, those whose mothers were HIV infected were reported to have more difficulties in all domains of psychosocial adjustment. Potential family processes that may explain the findings are discussed.

Achievement↗
PubMed1998

A QTL affecting milk yield and composition maps to bovine chromosome 20: a confirmation.

As part of a whole genome scan undertaken to detect quantitative trait loci (QTL) affecting milk yield and composition, we have genotyped a granddaughter design comprising 1152 sons for six microsatellite markers spanning bovine chromosome 20. An analysis performed across families provided strong evidence (experiment-wise P-values < 0.01) for the presence of a QTL affecting primarily protein percentage towards the telomeric end of the chromosome. A founder sire, shown in a previous study to segregate for a similar QTL in the corresponding chromosome region, was characterized by 29 and 57 sons and maternal grandsons, respectively, in the present design. Sorting corresponding sons and grandsons by paternal or grandpaternal allele provided significant evidence for the segregation of a QTL on chromosome 20. Altogether these results confirm the location of a QTL affecting milk production on bovine chromosome 20.

Animals↗
PubMed1998

Ischemic renal diseases: new insights into old entities.

Vascular nephropathies are a steadily increasing cause of end-stage renal failure. Arterionephrosclerosis and arteriolonephrosclerosis are common features in the hypertensive patient. This is especially true for blacks of African descent, in whom hypertension and nephrovasculopathies are a major cause of renal insufficiency. That primary hypertension leads to renal vascular lesions, glomerular obsolescence and interstitial fibrosis has long been established. It should not, however, obscure the fact that renal vascular lesions can be observed in animal models as well as in some humans, especially young blacks, in the absence of, or anticipating the onset of hypertension. This leads to considering the hypothesis that nephroangiosclerosis might stem from a genetic defect in the renal vascular bed and that this defect is strongly associated with the hypertensive trait. Atherosclerotic renal disease is a major, potentially treatable cause of chronic renal disease is a major, potentially treatable cause of chronic renal failure, especially in whites. It leads to renal atrophy, but the ischemic kidney retains a vigorous potential for tubular cell regeneration, which pleads for early recognition and treatment. Recent data suggest that renal ischemia, be it due to renal artery stenosis or to cholesterol crystal embolism, ranks among the multiple causes of secondary focal segmental glomerulosclerosis. Irrespective of its initial mechanism, ischemia induces renal fibrosis, the pathophysiology of which is centered on increased generation of angiotensin II. Finally, renal vascular lesions are commonly observed in the course of various nephropathies, even in the absence of hypertension, and the relationship between these lesions and the unfavorable prognosis of glomerulopathies, especially primary focal-segmental glomerulosclerosis, membranous glomerulopathy and IgA glomerulonephritis, remains to be elucidated. Expanding knowledge of the spectrum of nephrovasculopathies opens perspectives for investigating, understanding and treating a major mechanism of progressive renal insufficiency.

Humans↗
PubMed1998

Reversal of ventricular dilatation after correction of aortic incompetence: mechanical prosthesis compared with biological procedures.

BACKGROUND: The aim of the study was to compare early differences in reversal of LV dilatation between patients with mechanical prosthesis = group A (n = 51: Carbomedics = 40, Tekna/Edwards = 11) and biological procedures = group B (n = 75: pulmonary autograft = 36, aortic valve repair = 29, homograft = 10). METHODS: Since 1,990,126 consecutive patients younger than 50 years who had surgical correction of isolated aortic incompetence underwent echocardiographic examinations preoperatively, at discharge, and at one-year follow-up. Left-ventricular (LV) diameters were measured (LVEDD, LVESD) and matched to body surface area (LVESDI, LVEDDI and fractional shortening (FS) was calculated. Aortic peak flow velocities were assessed by Doppler technique and gradients were calculated. RESULTS: There were no significant differences preoperatively in aortic incompetence, NYHA classification, LVEDDI, LVESDI, and FS. In group B there was a significant decrease of LVESDI (p < 0.002) and LVEDDI (p < 0.001) but no change in FS at discharge. In group A a significant reduction of FS (p < 0.05) without any significant changes in LV size was observed. No patient died perioperatively or during the first year. At one-year follow-up (complete in 97.6% patients) there were no significant differences in LV diameters but group B had better ventricular function (p < 0.05) resulting in better NYHA classification (p < 0.05). Only group B had normal aortic valve gradients at discharge and at follow-up (A: 25.2 +/- 4.3 vs B: 10.2 +/- 2.4 mmHg). CONCLUSIONS: Normal aortic valve gradients in patients after aortic valve repair or allograft replacement for chronic aortic incompetence lead to early recovery from ventricular dilatation and significantly better ventricular function at discharge. One year postoperatively they had improved ventricular function and NYHA class in comparison with patients in whom a mechanical prosthesis was implanted.

Adult↗
PubMed1998

Long-term outcome according to renal histological lesions in 118 patients with monoclonal gammopathies.

BACKGROUND: The prognosis of monoclonal gammopathies with multiple myeloma and renal involvement is poor, and the indication for renal replacement therapy is controversial. Few studies address the value of renal histology for determining prognosis according to initial pathology findings. METHODS: We studied the course of 118 patients with multiple myeloma according to renal biopsy lesions. The monoclonal component was identified and quantified in serum and urine. Tumor cell mass was classified as stage 1, 2 or 3, according to Durie and Salmon. End-points were death, or survival on dialysis, or serum creatinine level at last examination. RESULTS: Renal biopsy showed myeloma kidney in 48 cases (41%), AL-amyloidosis in 35 (30%), light chain deposit disease in 22 (19%), chronic tubulointerstitial nephritis in 12 (10%) and cryoglobulinaemic kidney with multiple myeloma in 1. Maintenance haemodialysis was required in 46 patients (39%), earlier (P<0.0001) in myeloma kidney (mean: 3 months after diagnosis) than in AL-amyloidosis (mean: 15 months) and light chain deposit disease (mean: 18 months). Median survival was 12 months in myeloma kidney, 24 months in AL-amyloidosis and 48 months in light chain deposit disease. Dialysis increased survival in light chain deposit disease, in contrast with myeloma kidney and AL-amyloidosis patients whose survival was shorter when dialysed. The main cause of death during first year of dialysis was cardiac involvement in AL-amyloidosis, and sepsis or cardiac insufficiency in myeloma kidney. There was a trend to increased survival with multidrug chemotherapy which seemed to slow progression to end-stage renal failure. At last follow-up (median: 12 months, range 1-297), 65 (55%) patients had died. By multivariate analysis, independent predictors of survival were: age < 70, serum creatinine < or = 300 micromol/l, and serum calcium < or = 2.5 mmol/l. CONCLUSIONS: Initial renal biopsy helps predict prognosis in patients with multiple myeloma and renal involvement. Maintenance haemodialysis is a reasonable indication in light chain deposit disease and AL-amyloidosis, especially in patients aged < 70. Multidrug therapy tends to prolong survival and slow progression to end-stage renal disease.

Aged↗
PubMed1998

Adherence of Streptococcus pneumoniae to respiratory epithelial cells is inhibited by sialylated oligosaccharides.

To study carbohydrate-mediated adherence of Streptococcus pneumoniae to the human airway, we measured binding of live S. pneumoniae organisms to a cultured cell line derived from the lining of the conjunctiva and to primary monolayers of human bronchial epithelial cells in the presence and absence of oligosaccharide inhibitors. Both encapsulated and nonencapsulated strains of S. pneumoniae grown to mid-logarithmic phase in suspension culture adhered to cultured primary respiratory epithelial cells and the conjunctival cell line. Adherence of nine clinically prevalent S. pneumoniae capsular types studied was inhibited preferentially by sialylated oligosaccharides that terminate with the disaccharide NeuAc alpha2-3(or 6)Galbeta1. Adherence of some strains also was weakly inhibited by oligosaccharides that terminate with lactosamine (Galbeta1-4GlcNAcbeta1). When sialylated oligosaccharides were covalently coupled to human serum albumin at a density of approximately 20 oligosaccharides per molecule of protein, the molar inhibitory potency of the oligosaccharide inhibitor was enhanced 500-fold. The above-mentioned experiments reveal a previously unreported dependence upon sialylated carbohydrate ligands for adherence of S. pneumoniae to human upper airway epithelial cells. Enhanced inhibitory potencies of polyvalent over monovalent forms of oligosaccharide inhibitors of adherence suggest that the putative adhesin(s) that recognizes the structure NeuAc alpha2-3(or 6)Galbeta1 is arranged on the bacterial surface in such a manner that it may be cross-linked by oligosaccharides covalently linked to human serum albumin.

Bacterial Adhesion↗
PubMed1998

Granulomatous vulvitis, granulomatous cheilitis: a single diagnosis?

We report two cases of labial swelling (oral and vulvar) with a granulomatous histology in patients with a history of Crohn's disease. The differential diagnosis of granulomatous vulvitis and cheilitis, as well as the symptomatology and treatment of vulvar and oral Crohn's disease are further discussed. To our knowledge, reported cases of vulvar and oral Crohn's disease are quite scarce in the literature, but the disease might be underdiagnosed. We hope to contribute to an earlier recognition and a better management of the vulvar and oral mucocutaneous lesions of Crohn's disease.

Adult↗
PubMed1998

Digital image analysis of bone allograft union in sheep.

We compared the reliability of computer-assisted radiographic analysis (CARA) and visual evaluation of radiographs to assess host-graft junctions. 68 host bone/allograft junctions were obtained from an ongoing study on bone allografting in sheep. At 6 months, the grafted tibias were explanted and healing of the host-graft junctions were macroscopically determined. 49 junctions were macroscopically healed, whereas 19 had not united. 51 (0.8) of the junctions were correctly classified by radiographs, while 63 (0.9) of the junctions were correctly classified by CARA (p = 0.03). These findings warrant further evaluation in a clinical setting.

Animals↗
PubMed1998

[Intravascular malignant B-cell lymphomatosis with renal glomerular involvement: a case].

We report a case of intravascular malignant lymphomatosis observed in a 71 year-old male and characterised by the presence of a proteinuria in relation to the specific intraglomerular localisation. This malignant lymphoma, usually of the B phenotype, is rare and affects predominantly the central nervous system and the skin. Neoplastic cells home selectively to endothelium. Histological renal infiltration is frequent but a glomerular localisation, with proteinuria, is rare. The mechanism whereby lymphocytes home to endothelium cells is unclear but it could be related to the expression of lymphocyte-endothelium adhesion molecules. When present the nephrotic syndrome is associated with minimal change disease.

Aged↗
PubMed1998

[Ischemic renal diseases have become the most frequent causes of end stage renal disease in the elderly].

In the 80s it was established that atherosclerotic renal artery stenosis (ARAS) is a leading cause of renal insufficiency and that this condition ranks among the rare etiologies of chronic renal failure amenable to improvement or stabilization particularly in the white. Nephroangiosclerosis (NAS) is an increasing cause of ESRD in the western countries, especially in blacks. Epidemiological data on the vascular nephropathies leading to ESRD are still rare. In this study, we compare annual incidence of ESRD due to ARAS and NAS during two five-year periods: period A = 1982-1986, period B = 1992-1996. The region of the survey comprised 410,664 inhabitants (99.6% of Caucasians), of whom 100,230 were aged over 60 years. Diagnosis of ARAS required arteriography and that of NAS a renal biopsy. Undetermined vascular nephropathy was diagnosed when ESRD patients had had previously no arteriography or no histological examination. Major results were as follow (A vs B, incidence = n/million inhabitants): 1) Increasing incidence of ESRD due to all causes: 76 vs 95 per million, mean age at ESRD 56 vs 62 yrs, percentage of patients over 65 yrs 28 to 59% (p < 0.001). 2) Increasing incidence of ESRD due to vascular nephropathies: 5.5 vs 27.5 per million (p < 0.0001) in general population and 22 vs 110 per million (p < 0.0001) in population aged over 60 years, mean age at ESRD 68 vs 73 yrs. 3) Increasing incidence of different types of ischemic renal diseases leading to ESRD: ARAS 2.5 vs 15 per million (p < 0.0001) in general population and 10 vs 60 per million (p < 0.001) in those aged over 60 yrs, mean age 69 vs 74 yrs, NAS: 1 vs 8 and 4 vs 32 per million (p < 0.001), mean age 67 vs 72 yrs, undetermined VN 0.5 vs 2.5 and 2 vs 10 per million, 65 vs 73 yrs. Our study demonstrates that ischemic renal diseases 1) have become the most frequent causes of ESRD (27% of all patients and 43% of those aged over 6C years) in the Caucasian elderly. 2) are the only cause of increasing incidence of ESRD in this French region.

Aged↗