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Biomedical subjects

A M el Nahas

Publications and source records attributed to A M el Nahas.

At least 19 recordsLinked to original sources
PubMed2000

Medical illustration in the UK: its current and potential role in medical education.

This paper describes how medical illustration has evolved to become increasingly important in undergraduate medical education, postgraduate medical education and continuing medical education, as new technologies have become available and new teaching methods have developed based on the emerging technologies. It also examines how the role of the medical illustrator has changed. The descriptor 'medical illustration' fails to reflect the changing face of the profession and it is suggested that a new title is required to convey better the evolving role of the profession.

Education, Medical↗
PubMed1997

Renal fibrosis: insights into pathogenesis and treatment.

The progression of chronic renal failure is characterised histologically by glomerulosclerosis, tubulointerstitial fibrosis and vascular sclerosis. Recent research has identified common mechanisms underlying these fibrotic processes. In particular, the scarring process within the glomeruli and the tubulointerstitium involves the infiltration by inflammatory cells including monocytes, the activation of intrinsic renal cells as well as interactions between infiltrating and resident cells. These interactions depend, to a large extent, on the release by these cells of chemokines, cytokines and growth factors. These factors are in turn involved in the induction of cellular proliferation within the kidney and the stimulation of the synthesis and deposition of extracellular collagenous matrix. Fibrosis is believed to result from excessive synthesis of extracellular matrix and a concommitant decrease in its breakdown. This fibrotic process resulting in end stage renal insufficiency bears strong similarities to that taking place within cirrhotic livers or fibrotic lungs. The new insights in our understanding of renal fibrosis have opened the way to new interventions aimed at its prevention. This may ultimately slow the progression of chronic renal insufficiency and decrease the number of patients requiring dialysis replacement therapy.

Animals↗
PubMed1997

Myofibroblasts and the progression of diabetic nephropathy.

BACKGROUND: The cellular mediators of progressive renal fibrosis in diabetic nephropathy remain unknown. Myofibroblasts have been implicated in the pathogenesis of experimental and clinical renal fibrosis. Their role in the progression of diabetic nephropathy is the subject of this study. SUBJECTS AND METHODS: We have studied by immuno-histochemistry the expression of cytoskeletal proteins associated with the activation of myofibroblasts; alpha-smooth-muscle actin (alpha-SMA), vimentin (Vi) and desmin (D), in the kidneys of 25 patients with diabetic nephropathy (5 patients had a superimposed glomerulonephritis). Comparisons were made with normal tissue from three kidneys removed for renal-cell carcinoma. Correlations were studied between clinical and biochemical parameters with the expression of renal cytoskeletal proteins. RESULTS: In normal kidneys, cells expressing alpha-SMA were confined to the vascular media and adventitia while immunoreactive Vi was detected in glomerular epithelial cells. In diabetic kidneys, cells expressing alpha-SMA were detected primarily in the renal interstitium and to a lesser extent in some glomeruli in association with mesangial proliferation. Vimentin immunostain decreased in glomeruli displaying diabetic hyalinosis and sclerosis. By contrast, strong Vi immunoreactivity was noted in atrophic diabetic tubules and to a lesser extent in the interstitium. Desmin was not detected in either normal or diabetic kidneys. Close correlations were observed between the expression of renal cytoskeletal proteins and the progression of renal insufficiency. Interstitial alpha-SMA proved to be a predictor of progressive diabetic nephropathy (R2 for 1/serum Cr slope = 0.608, P = 0.00001). This predictive value was superior to, and independent from, that of the best conventional histological predictive parameters; tubular atrophy (R2 = 0.477, P = 0.00004) and interstitial fibrosis (R2 = 0.28, P = 0.001). CONCLUSION: We have demonstrated in this study the neoexpression of cytoskeletal proteins within diabetic kidneys. This has allowed the identification of new predicting histological markers for the progression of diabetic nephropathy.

Actins↗
PubMed1997

Myofibroblast phenotypes expression in experimental renal scarring.

BACKGROUND: Myofibroblasts have been implicated in the pathogenesis of wound healing and tissue fibrosis. A role has also been put forward for these cells in the development of experimental and clinical renal scarring. SUBJECTS AND METHODS: We examined the expression of myofibroblast phenotypes by immunohistochemistry, relying on an avidin-biotin-peroxidase method, during the course of renal scarring in rats submitted to subtotal (5/6) nephrectomy (SNx). We also attempted to identify changes in immunoreactive transforming growth factor-beta (TGF-beta) and collagen (III and IV) within remnant kidneys in order to determine their association with the expression of the myofibroblasts. RESULTS: In normal sham-operated rats, alpha-smooth muscle actin (alpha-SMA) was confined to the media of renal arteries and arterioles. In contrast, in rats with renal ablation we observed the early (day 7) appearance of myofibroblasts expressing alpha-SMA (A) in the interstitium of remnant kidneys particularly around vessels. Interstitial cells expressing alpha-SMA increased with time as tubulointerstitial fibrosis progressed. By day 30 some interstitial cells also expressed vimentin (V). Various interstitial myofibroblast phenotypes (A, V, VA) were expressed during the course of experimental renal scarring. Interstitial myofibroblasts appeared to be associated with TGF-beta as these cells' cytoplasm stained for both this growth factor and alpha-SMA. Interstitial fibrosis was also associated with increased interstitial expression of both collagen III and IV. Some atrophic tubular cells showed positive immunostaining for vimentin during the late stages of renal scarring (days 90-150). In the glomeruli, a segmental expression of alpha-SMA was noted from day 21 after SNx onward. Normal glomerular endothelial cells appeared to express vimentin while epithelial cells expressed both vimentin and desmin (D). The glomerular immunostain for vimentin increased with time but decreased as glomerulosclerosis progressed. In contrast, glomerular desmin and alpha-SMA immunostain continued to rise with progressive glomerulosclerosis. This was associated with the appearance of type III collagen within scarred glomeruli. Both vimentin and desmin appeared within the walls of the renal arterioles and increased with time from day 7 and 15, respectively. Vimentin was also expressed in the peritubular capillaries of remnant kidneys. By contrast, alpha-SMA, normally present in the media of arterioles, decreased as arteriolar sclerosis progressed. These changes cannot be exclusively attributed to systemic hypertension as they were absent in a group of age-matched, sham-operated, spontaneously hypertensive rats. DISCUSSION: Myofibroblasts may play a role in the pathogenesis of glomerulosclerosis, tubulointerstitial fibrosis and vascular sclerosis. Further, the acquisition of new myofibroblastic phenotypes by glomerular and tubular cells may contribute to renal fibrosis.

Actins↗
PubMed1997

Urinary and serum type III collagen: markers of renal fibrosis.

BACKGROUND: The progression of chronic renal failure is characterized by the progressive fibrosis of the kidneys. Such fibrosis reflects the increased deposition of collagens (I, III, and IV) as well as fibronectin within scarred kidneys. In this study, we determined whether changes in renal extracellular matrix (ECM) components are reflected by parallel changes in their circulating or urinary levels. PATIENTS AND METHODS: We studied 40 patients with a range of subacute and chronic nephropathies who underwent a renal biopsy. At the time of the biopsy, their serum and urinary levels of collagens III (amino terminal peptide of procollagen III; PIIINP) and IV, as well as fibronectin were measured. Clinical, biochemical and histological parameters were correlated. Multiple regression analysis was applied to determine the predictive value of circulating and urinary ECM components for the severity of renal fibrosis. RESULTS: We noted an increase in circulating and urinary levels of collagens III and IV but not fibronectin in patients with nephropathies compared to healthy volunteers. Increased immunoreactivity for these ECM components was also detected in kidney biopsies when compared to normal kidneys. A strong positive correlation was detected between circulating and urinary procollagen III (PIIINP) and the severity of renal interstitial fibrosis (serum PIIINP: r = 0.49, P < 0.01; urine PIIINP: r = 0.51, P < 0.01). CONCLUSION: We conclude that the measurements of urinary collagen III (PIIINP), and to a lesser extent serum collagen III (PIIINP), are useful indicators of the extent of renal fibrosis. This may have diagnostic implications and may prove useful for the monitoring of disease progression.

Adolescent↗
PubMed1997

Cytokines and the malnutrition of chronic renal failure.

Malnutrition in uremic patients remains one of the major causes of morbidity and mortality. Its mediators remain largely unknown. Uremia is characterized by changes in circulating levels of catabolic cytokines and anabolic growth factors. The aim of this study was to investigate whether these changes are associated with the malnutrition of patients with chronic renal failure (CRF). We have studied the prevalence of malnutrition in a small group of patients (n = 20) with CRF (serum creatinine = 551 +/- 105 mumol/l, mean +/- SD) and 25 age-matched controls. Nutritional status was assessed by dietary diaries, subjective global assessment (SGA), and by measurement of anthropometric parameters. Regression analysis was applied to examine the relationship between biochemical and anthropometric parameters. Simultaneously, we have investigated changes in the circulating levels of catabolic cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta and IL-6] and an anabolic growth factor [insulin-like growth factor-I (IGF-I)]. We observed a high prevalence of malnutrition as judged initially by SGA: 50% moderately malnourished and 15% severely malnourished. This was confirmed by anthropometric measurements. We noted a significant reduction in both triceps skinfold thickness (TST; 35% of patients < 25th centile) and midarm muscle circumference (MAMC, 65% of patients < 25th centile). We also noted a reduction in serum IGF-I in malnourished patients (IGF-I in well-nourished patients = 207 +/- 48 micrograms/l, in malnourished patients = 133 +/- 33 micrograms/l, p < 0.01). IGF-I correlated with TST (r = 0.71, p < 0.001) and MAMC (r = 0.47, p < 0.05). IGF-I had a high predictive value for TST (R2 = 51%, p < 0.001). In contrast, TNF-alpha levels were higher in malnourished patients: 19.5 +/- 30 pg/ml compared to 3.9 +/- 8 pg/ml in healthy patients (p < 0.001) and TNF-alpha showed a negative correlation with MAMC (r = -0.69, p < 0.01; R2 = 47%, p < 0.01). IL-1 beta levels were higher in CRF than in controls but did not correlate with nutritional parameters. No significant changes could be detected in serum IL-6. A significant percentage of predialysis patients with CRF suffer from some degree of malnutrition. This may be attributed in part to a fall in circulating anabolic growth factors and an increase in catabolic cytokines.

Adult↗
PubMed1997

Progression of renal scarring: a balancing act.

The progression of renal scarring and fibrosis is a complex process involving intricate interactions between a wide range of pro-scarring and anti-scarring forces and mediators. A better understanding of these events should allow more rational interventions based on their manipulations. Unfortunately, while rapid and considerable progress has been made in experimental animals and in the rat in particular, these so far have had a limited impact on progressive nephropathies in humans. It is as if clinical interventions continue to proceed along different lines, defined decades ago.

Animals↗
PubMed1996

Renal function and morphometry in the dwarf rat following a reduction in renal mass.

BACKGROUND: The compensatory increase in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) which follows a reduction in renal mass may be mediated by growth hormone, a renal vasodilator. METHODS: GFR, ERPF and glomerular morphometry were assessed in the dwarf rat, selectively deficient in GH, and compared its Lewis base strain. Studies were performed 21-days after sham-operation, unilateral nephrectomy or subtotal nephrectomy in age-matched animals. GFR and ERPF were assessed from the renal clearance of inulin and p-aminohippurate measured under barbiturate anaesthesia. RESULTS: The dwarf rat had a lower GFR and ERPF than the Lewis rat, in proportion to its lower body weight and lower kidney weight. Kidneys from the dwarf rat had a similar number of glomeruli to the Lewis, but smaller glomerular components in proportion to a lower kidney weight. Following unilateral nephrectomy, GFR (dwarf + 58%, Lewis + 53%) and ERPF (dwarf + 58%, Lewis + 52%) increased to a similar degree in both rat strains. Glomerular diameter, volume and capillary surface area increased in proportion to kidney growth, although compensatory renal growth (dwarf + 62%, Lewis + 78%) was somewhat lower in the dwarf. Following 5/6 subtotal nephrectomy, GFR (dwarf + 143%, Lewis + 171%) increased to a similar degree in both rat strains while ERPF (dwarf + 108%, Lewis + 48%) and compensatory renal growth (dwarf + 115%, Lewis + 86%) were greater in the dwarf than the Lewis rat. Subtotal nephrectomy was also associated with an increase in the thickness of the glomerular basement membrane in both rat strains. CONCLUSIONS: The results do not support a role for GH in the compensatory increase in renal function or hypertrophy which follows a reduction in renal mass, excluding this as a potential mechanism for GH-dependent renal scarring.

Animals↗
PubMed1996

The effect of rhubarb extract on experimental renal fibrosis.

In order to explore the therapeutic potential of traditional Chinese medicinal herbs on the progression of experimental chronic renal failure (CRF), we have studied the effect of orally administered rhubarb extract on the course of CRF in rats submitted to subtotal nephrectomy (SNx). Adult male Wistar rats were submitted to either a SNx (n = 18) or a sham operation (n = 10). Thirty days after SNx, nine SNx and five sham operated rats were given aqueous rhubarb roots extract (150 mg/day) in drinking water. The rats were followed up for 120 days. Rhubarb treatment had no effect on the systemic hypertension observed in SNx rats. Rhubarb-tested SNx rats had significantly less proteinuria 90 days (172 +/- 63 mg/24 h) and 120 days (228 +/- 92 mg/24 h) after SNx when compared to untreated SNx controls (day 90, 246 +/- 80 mg/24 h; day 120, 335 +/- 113 mg/24 h, P < 0.05). Renal function was comparable in rhubarb-treated and untreated SNx rats. However, at sacrifice the severity of glomerulosclerosis was significantly reduced in SNx rats treated with rhubarb (2.03 +/- 0.44; SNx controls, 2.58 +/- 0.53, P < 0.05). The difference in tubulointerstitial scarring between the two groups did not reach significance. Our results suggest that rhubarb extract reduces proteinuria and the severity of glomerulosclerosis in rats with remnant kidneys.

Animals↗
PubMed1995

Cyclosporine enhances the expression of TGF-beta in the juxtaglomerular cells of the rat kidney.

The mediators of cyclosporine (CsA) nephrotoxicity remain ill defined. In this study, we describe evidence of increased amounts of transforming growth factor-beta (TGF-beta) in the kidneys of adult male Wistar rats treated with CsA (5 to 25 mg/kg/day) for four weeks. Localization of TGF-beta was undertaken immunocytochemically at both light and electron microscope levels and Northern blot analysis was applied to detect changes in transcription of TGF-beta. In control rats, weak to moderate immunostaining for TGF-beta was observed, in the juxtaglomerular arterioles. CsA treatment resulted in a dose-dependent increase in the number of stained afferent and interlobular arterioles and in the intensity of staining. The number of stained afferent arterioles increased from a control value of 0.21 +/- 0.08/mm2 cortex to 0.84 +/- 0.15/mm2 cortex, P < 0.01, and to 1.12 +/- 0.10/mm2 cortex, P < 0.01, in rats treated with CsA 12.5 mg/kg/day and 25 mg/kg/day, respectively. The number of interlobular arterioles stained for TGF-beta increased from a control value of 0.07 +/- 0.05/mm2 to 0.31 +/- 0.02/mm2, P < 0.05, and 0.39 +/- 0.07/mm2, P < 0.01, in rats treated with CsA, 12.5 mg/kg/day and 25 mg/kg/day, respectively. At the electron microscope level, TGF-beta was localized exclusively within the granular cells of the juxtaglomerular arterioles. Northern blot analysis suggested that this enhanced staining is due to increased transcription of TGF-beta 1. We have therefore observed an association between TGF-beta and CsA-induced nephrotoxicity. While this does not establish a causal link, it leads us to postulate that TGF-beta, alone or in combination with other growth factors, may play a role in the pathogenesis of CsA induced nephrotoxicity.

Animals↗
PubMed1995

Nutritional profile of continuous ambulatory peritoneal dialysis patients.

Undernutrition in dialysis patients contributes to their morbidity and mortality. This is a cross-sectional study of the nutritional status of 61 patients treated with continuous ambulatory peritoneal dialysis (CAPD). They were studied with emphasis on assessment of their nutritional intake, anthropometric measurements, and evaluation of biochemical parameters. The correlation between the rate of CAPD peritonitis and these measurements was also examined. The majority of the patients (63.1%) had inadequate protein intake ( < or = 1.2 g/kg/day). A comparable percentage had a low energy intake ( < or = 30 kcal/kg/day). Moderate malnutrition, as assessed by a low triceps skinfold thickness (TST) or a reduced midarm muscle circumference (MAMC) of < or = 20th percentile, was detected in 52% and 39% of the patients, respectively. Severe malnutrition (TST or MAMC < or = 10th percentile) was present in 36% of the patients. The serum insulin-like growth factor I (IGF-I) proved to be the most useful biochemical marker of malnutrition. It showed a positive correlation with TST (r = 0.325; p < 0.05). No significant correlation was observed with other short-life proteins such a transferrin or prealbumin. However, stepwise regression analysis showed the predictive value of serum IGF-I for anthropometric values to be low (adjusted R2 = 34.6%). Wasted patients did not appear to have more infections when compared to their healthier counterparts. However, a weak correlation was observed between TST and the number of peritonitis episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Anthropometry↗
PubMed1995

Relationship between the diuretic effect of radiocontrast media and their ability to increase renal vascular resistance.

The relationship between diuresis and natriuresis induced by radiocontrast media (RCM) and their renal haemodynamic effects were investigated. The effects of the iso-osmolar iotrolan and the hyperosmolar diatrizoate on the renal vascular resistance (RVR) were studied in the filtering and non-filtering variants of the isolated perfused rat kidney (IPRK) preparation. In the non-filtering model, no tubular regulatory process can be activated. The effect of diatrizoate on the RVR of the filtering IPRK in the presence of fursemide (0.3 mmol l-1) an inhibitor of the tubuloglomerular feedback (TGF) was also investigated. There was no significant difference (p > 0.05) in the response of the filtering (n = 6) and non-filtering (n = 6) IPRK to iotrolan. The induced reduction in the renal perfusate flow (RPF) by iotrolan was 20.5 +/- 3.05% and 22.9 +/- 3.03%, respectively. The reduction in the RPF which was observed with diatrizoate in the non-filtering IPRK (n = 5, 17.5 +/- 3.04%) was significantly less (p < 0.05) in comparison to that of the filtering IPRK (n = 6, 26.9 +/- 4.28%). In the frusemide experiments, a reduction in the RPF comparable to that of the non-filtering kidney was observed (n = 5, 13.7 +/- 4.34%). This study demonstrates that the renal vascular effect of diatrizoate is partially dependent on the TGF response. No tubular regulatory mechanism was accountable for the haemodynamic effect of iotrolan. The activation of the tubular response is osmolarity dependent.

Animals↗
PubMed1995

Platelet-derived growth factor in experimental glomerulonephritis.

Growth factors and in particular platelet-derived growth factor (PDGF) have been implicated in the pathogenesis of glomerulonephritis and glomerulosclerosis. We have studied the distribution of immunoreactive PDGF (iPDGF) within serial kidney biopsies (days 7, 15, 30, 90 and 120) of eight rats with an accelerated form of nephrotoxic serum nephritis (NTN). The course of NTN was mild in five rats and seere in three. Two patterns of immunostain for PDGF were noted. The first consisted of iPDGF-B chain in a glomerular segmental distribution similar to that of infiltrating monocytes (OX6+cells). At all stages of NTN the distribution of iPDGF-B chain correlated closely with the immunostain for monocytes. The second pattern of immunostain showed iPDGF-A chain in a diffuse distribution along the glomerular capillary lining and to a lesser extent in some mesangial cells. In severely affected rats the magnitude of the iPDGF-A increased along with glomerulosclerosis but disappeared later from areas of segmental and global glomerular obsolescence. By contrast, in rats with milder NTN glomerular iPDGF-A chain peaked early and decreased subsequently.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Subtotal nephrectomy: a mosaic of growth factors.

We have studied the distribution of immunoreactive growth factors, by an avidin-biotin-peroxidase technique, throughout the course of progressive renal scarring in rats submitted to extensive renal ablation. Groups of rats (n = 6) were sacrificed at Days 7, 15, 21, 30, 90 and 150 following subtotal nephrectomy (SNx) by ligation and resection of the renal poles. During the early stages, when compensatory renal growth took place, increased renal immunostaining for insulin-like growth factor-I (IGF-I) and epidermal growth factor (EGF) was detected within the collecting ducts and distal tubules, respectively. As renal scarring became established by Days 90 and 150, these two growth factors were detected within the cells of damaged and vacuolated distal tubules. By contrast, a progressive increase immunostain for platelet-derived growth factor (PDGF)-AB was apparent within the glomeruli from Day 15 onward preceding the onset of glomerulosclerosis. A third staining pattern was apparent by Day 15 for transforming growth factor-beta (TGF-beta) and by Day 30 for IGF-I consisting of a perivascular and interstitial distribution coinciding with adventitial expansion and tubulo-interstitial fibrosis, respectively. A mosaic of growth factors is expressed within the kidneys of rats submitted to extensive renal ablation.

Animals↗