The correlation of genetic markers with anatomoclinical and histopathological forms in Hirschsprung's disease.

Hirschsprung's disease is a birth defect that affects about one out of 5000 newborns. It is one of the most common causes of intestinal obstruction at the babies. The objectives of this study are to evaluate the characteristics of Hirschsprung's disease in Dobrogea area, test of genetic markers in families and single cases, estimate the value of the test in the diagnosis and for evolution. We made a case-control study for the period 1995-2006 and analyzed 21 cases of Hirschsprung's disease, which were treated in the Emergency County Hospital, Constanta. The diagnostic methods comprised clinical and paraclinical examination. The chromosomal markers used in the study are represented by four categories of chromosome abnormalities: Trisomy 21, Del 10q, Del 13q, Del 17q. The molecular markers investigated by us are represented by: RET, EDNRB and EDN3. We made the correlation of genetic markers with the anatomopathological and histopathological forms, by measuring the level of association, expressed by the calculated relative risk (OR) and using the correlation index f. Based on data obtained from the group investigated, we found that the indices of association and correlation are consistently higher compared to DNA-markers with chromosomal markers, both for anatomopathological forms as well as histopathological. We noticed that no chromosomes markers were recorded with indices of correlation with negative values, which means that these chromosomal abnormalities are involved with a particular quota to the release of disease.

Graphene Oxide-Assisted Morphology and Structure of Electrodeposited ZnO Nanostructures.

In this paper, ZnO electrodeposition was studied with the presence of graphene oxide (GO) exploited as a possible structure-directing agent. The effect of deposition potential and duration on the morphology and structure of ZnO was analyzed. The morphology and structure of the hybrids was analyzed by Raman spectroscopy, X-ray diffraction (XRD), and Scanning Electron Microscopy (SEM). The Raman results indicate a successful modification of ZnO with GO sheets and a hybridization threshold of 10 mg L-1 by the evolution of the defect related band of ZnO at 580 cm-1. The morphology results show that a low GO content only slightly influences the morphology and orientation of ZnO nanostructures while a high content as 10 mg L-1 changes the morphology in nanoplates and growth orientation to lateral. The results show that while GO participated in the deposition reaction, it has a two-fold role, also by structure-controlling ZnO, indicating that the approach is valid for the use of GO as a structure-directing agent for the fabrication of ZnO nanostructures by electrodeposition with varying morphologies and orientations.

[Association of Wolff-Parkinson-White syndrome with isolated non-compaction of the left ventricle: a case report]. / Association du syndrome de Wolff-Parkinson-White a une non-compaction isolée du ventricule gauche. A propos d'un cas.

The Wolff-Parkinson-White syndrome (WPW) may be associated with a number of cardiac pathologies, especially congenital disease, in 7.5 to 17% of cases. The authors report a rare association of the WPW syndrome with two Kent bundles, right and left septal, with non-compaction of the left ventricle in a 52 year old man. This was a chance finding during systematic echocardiography after ablation, and confirmed by cardiac MRI. The patient was asymptomatic.

Recurrence of Fabry's disease in a renal allograft eleven years after successful renal transplantation.

A case of Fabry's disease in a renal transplant recipient with a follow-up period of 11 years is reported. The patient suffered from renal, skin, peripheral nerve lesions, and asymptomatic cardiomegaly. Fabry's disease symptoms disappeared after transplantation. Improvement of renal function was rapidly observed, and it remained satisfactory during the whole posttransplantation period. The patient died of a severe, uncontrolled infection and of biliary peritonitis. Autopsy showed a polyvisceral accumulation of sphingolipids deposits. The engrafted kidney was histologically free of disease. Ultrastructurally, it revealed numerous sphingolipid inclusions in the endothelial cells of capillaries. The explanation of this complication could be attributed to: (1) high circulating levels of plasma substrates locally overwhelming the enzymatic capability of the graft endothelial cells; and (2) the endothelial cells originated from the recipient but not from the donor, an occurrence that has been described after transplantation. Rejection and the newly formed deposits in the endothelial cells may lead to the loss of the engrafted organ. As a consequence of the increasing possibility of organ transplantation, this complication should be detected by studying the blood vessels ultrastructurally in order to evaluate the condition of the transplant.

Granzyme B-gene expression: a marker of human lymphocytes "activated" in vitro or in renal allografts.

Human killer cells contain cytoplasmic granules in which serine esterases, or granzymes, and perforin have been identified. We have studied the induction of granzyme B-gene expression in peripheral blood lymphocytes and large granular lymphocytes activated by various stimuli in vitro as well as in cellular infiltrates at the site of renal allografts in patients with and without rejection. Using in situ hybridization, kinetic experiments have shown that granzyme B mRNA is an early marker of in vitro cell activation. Data obtained in vivo also indicate the presence of granzyme B mRNA-bearing cells, which argues in favor of the induction of granzyme B gene in cells activated in vivo.

Liver granulomatosis is not an exceptional cause of hypercalcemia with hypoparathyroidism in dialysis patients.

In 4 of our patients on chronic dialysis, we were intrigued by the association of hypercalcemia +/- hyperphosphatemia and normal intact PTH, with anicteric cholestasis without cytolysis. This picture occurred in 2 patients after they resumed dialysis because of a transplant rejection and in a third one after discontinuation of corticosteroids, prescribed for an idiopathic thrombocytopenia. No patient was under calcitriol, CaCO3 therapy, and their hypercalcemia persisted on a low calcium dialyzate (1.25 mmol/l). Obvious etiologies of hypercalcemia were not found: vitamin D or A intoxication, hyperparathyroidism, aluminum intoxication, hemopathy, HIV infection. The hypothesis of a granulomatous disease was made and a liver biopsy was performed showing granulomas with giant epitheloid cells. In one case foreign material (silicon ?) was present in the macrophages. Extensive investigations for sarcoidosis, tuberculosis and mycosis were negative. In 2 cases the so-called "dialysis" granulomatosis actually occurred in transplanted patients, suggesting the role of a transplantation related factor (toxic or virus). In the last case HCV seroconversion was present. In the 4 cases, corticotherapy led to the disappearance of hypercalcemia and to an increase of PTH. Our patients had the biological pattern of low bone turnover disease (hypercalcemia and normal intact PTH) and bone biopsy performed in 2 showed osteomalacia or ABD without aluminum. The association of this pattern with cholestasis should evoke liver granulomatosis, which should be confirmed by a liver biopsy and lead to a treatment by corticosteroids. The masking effect of previous corticoid therapy for transplantation should be pointed out. In 2 cases serial monitoring of plasma calcitriol showed a relation between decreasing high normal calcitriol with prednisone and normalization of calcemia, suggesting the role of inappropriate synthesis of calcitriol by the granuloma. In conclusion, liver granulomatosis should be looked for in dialysis patients on the association of unexplained hypercalcemia and normal PTH with anicteric cholestasis, and confirmed by a liver biopsy. Although still of unknown etiology, its evolution is favourable under corticotherapy.

Risk factors of renal failure progression two years prior to dialysis.

AIM: The respective contribution of sex, type of nephropathy, degree of proteinuria, blood pressure, protein and sodium daily intakes, blood lipid profile, protidemia, hemoglobinemia, acidosis and CaPO4 product on the rate of renal failure progression is debated. PATIENTS AND METHODS: The link between these parameters and the decrease of creatinine clearance, deltaCcr (according to Cockroft) was assessed in uni- and multivariate analysis in a population of 49 patients (26 women; age 60+/-15 years, weight 79+/-15 kg) selected out of 173 presently treated hemodialysis patients on the basis of availability of a quarterly follow-up for 2 years before starting dialysis. The patients were advised a moderate protein and salt restriction which could be retrospectively assessed (on urinary excretion of urea and sodium) at, respectively, 0.82 g/kg/day and 6.5 g/day. RESULTS: The 2-year deltaCcr was 14+/-14 ml/min. It was not different in men and women. This decrease in Ccr was neither significantly different in gomerular disease (17+/-8, n = 14), diabetic nephropathy (12+/-6, n = 7), nephroangiosclerosis (15+/-8, n = 5), interstitial nephritis (12+/-10, n = 14), and PKD (11 +/-12, n = 9). Patients with antihypertensive drugs (n = 42) had a faster progression than those without drugs (n = 7): deltaCcr = 15+/-14 vs 7+/-7 ml/min (p < 0.05) in spite of comparable blood pressure but with higher proteinuria. Linear regression of deltaCcr with the initial and 2-year averaged values of the quantitative parameters showed a significant positive link for both values with cholesterol, hemoglobine and proteinuria and a negative one with protidemia. A positive link was observed with the initial value of bicarbonate and the 2-year mean of diastolic and mean blood pressures. No link at all was observed with urea and Na excretion, CaPO4 product and triglycerides. Multiple regression disclosed a significant link only for protidemia (negative with both initial and 2-year averaged value), diastolic BP (only for the 2-year averaged value and hemoglobinemia (for the initial value). When the patients were classified according to a threshold value of their protidemia, DBP, hemoglobinemia, and cholesterolemia those with the combination of 2 risk factors of progression (protidemia > or = 66 g/l, DBP > or = 90 mmHg, hemoglobinemia > 11 g/dl, proteinuria > or = 3 g/d, CT > 5 mmol/l) had a significantly greater decrease of Ccr than those with the 3 other combinations at the exception of the association of low protidemia with DBP. CONCLUSION: Diastolic hypertension and low protidemia are the 2 most important factors predicting progression of renal failure. A predictive synergy was furthermore pointed out between low protidemia or diastolic hypertension with proteinuria and cholesterol. On the contrary anemia attenuates progression linked to low protidemia, diastolic hypertension, proteinuria and high cholesterol.

[Could angiotensin II type I receptor antagonists have a superior beneficial effect than that of angiotensin II converting enzyme inhibitors with respect to the risk of cerebrovascular accident?]. / Les antagonistes des récepteurs de type 1 de l'angiotensine II peuvent-ils avoir un effet bénéfique supérieur à celui des inhibiteurs de l'enzyme de conversion vis-à-vis du risque d'accident vasculaire cérébral?

In contrast with the expected results, the Captopril Prevention Project study has found that the relative risk of stroke was greater by 25% in patients treated with ACEI than in patients receiving the conventional diuretics +/- betablockers regimen (Hanson et al. ISH Amsterdam, June 98). This difference persisted after adjustment for the initial differences of blood pressure levels between the groups after randomisation. This does not mean that ACEI would worsen the risk of stroke when compared to a placebo, since a potent protective effect of diuretics and betablockers on the relative risk of stroke has long been demonstrated. Nonetheless, these results suggest that for a similar blood pressure lowering effect, conventional therapy is more effective than ACEI to prevent stroke. This finding, in discrepancy with the current prevailing opinion that ACEI have emerged as the most effective preventive treatment to reduce cardiovascular morbidity, is regarded as surprising by the investigators. However, a number of animal experimental data may help to envisage the complete inhibition of angiotensin II formation as a two-edged sword, because of the multiplicity of its receptors mediating different, and even opposite effects. In a series of experimental studies in mammals, the group of Fernandez has provided a bundle of observations suggesting that angiotensin II contributes to early reperfusion following acute ischemia by enabling the recruitment of pre-existing collateral vascularisation, an effect mediated via the stimulation of non-AT1 receptors (possibly AT2). Indeed, the worsening of stroke in the gerbil after incomplete ligation of the carotid by pre-treatment with ACEI had been demonstrated by these authors (J Cerebral Blood Flow Metab, 1988; 24:937), and they further show that pre-administration of losartan significantly reduced the ischemic brain damage and the mortality induced by the abrupt ligation of one carotid, but that this preventive effect of losartan was abolished if enalapril was co-administrated (J Cardiovasc Pharmacol 1994; 24:937). The first available clinical data on stroke risk with ACEI reported in the CPP study, showing a less effective prevention of stroke with ACEI than diuretics supports the hypothesis that similar mechanism may also prevail in humans, and lead us to propose to discuss the rationale for a large multicentric trial aiming to compare the protective effect of ARAT1 and ACEI on the risk of recurrence of stroke.

[Periarteritis nodosa complicated by intrapancreatic vascular rupture]. / Périartérite noueuse compliquée d'une rupture vasculaire intra-pancréatique.

Clinical pancreatic manifestations are unusual in polyarteritis nodosa. A case of intrapancreatic hemorrhage due to vascular rupture occurring during the course of histologically proven polyarteritis nodosa is described. The patient presented with massive hemoperitoneum requiring emergency laparotomy. Splenopancreatectomy was performed to control bleeding. Steroid therapy was continued during the postoperative course, with favorable outcome. The mechanism of vascular rupture is not clear, but is probably related to focal arteritis with consequent infarction. No ruptured microaneurysm was found in this case.

[Collapsing glomerulopathy and cytomegalovirus, what are the links?]. / Glomérulopathie avec collapsus du floculus et cytomégalovirus, quels liens?

BACKGROUND: Collapsing glomerulopathy is a form of focal and segmental glomerulosclerosis which occurs preferentially in black people. It causes severe nephrotic syndrome and quickly progresses towards end-stage renal failure. CASE REPORT: We report the case of a 16-year-old black girl from Guadeloupe who was admitted for tetanus and edema in 1996. She had hypoparathyroidism, renal failure and a nephrotic syndrome as well as cytomegalovirus infection. Renal biopsy showed collapsing glomerulopathy. The renal function improved on glucocorticoid and ganciclovir therapy and her serum creatinine stabilized around 250 mumol/l for two years. DISCUSSION: Collapsing nephropathy is the cellular type of focal and segmental glomerulosclerosis. The main etiology is the human immunodeficiency virus. A viral infection may be involved in its pathogenesis. Other viruses could be linked with this nephropathy. This case report relates a case associated with a cytomegalovirus viruria. The clinical course might be related with the antiviral treatment.

[Emphysematous pyelonephritis associated to urogenital tuberculosis]. / Pyélonéphrite emphysémateuse associée à une tuberculose urogénitale.

Emphysematous pyelonephritis is a rare condition which in most cases occurs as a result of Escherichia coli infection of the urinary tract in patients known as being diabetic. The gas-filled abscesses carry a high mortality rate, especially when the antibiotic treatment is not combined with early surgery. We report a case where the failure of medical treatment led to curative nephrectomy. Unusually, diabetes was revealed by the pyelonephritis. Another particularity of this case was that the emphysematous pyelonephritis was associated with genitourinary tuberculosis. This association, of which no other example could be found in the literature, is discussed.

[Renal and hypertensive complications of extracorporeal lithotripsy]. / Complications rénales et hypertensives de la lithotritie extracorporelle: les patients à risque.

HISTOLOGICAL AND FUNCTIONAL CONSEQUENCES OF ESWL: Extracorporeal shock wave litotripsy is now used for the treatment of about 90% of stones. Because of the nonpunctual delivery of energy into the stone, a small volume of renal parenchyma is injured, giving rise to a fibrous scar which can be visualized by morphological techniques such as magnetic nuclear resonance. Isotopic techniques point out a 15% reduction of renal plasma flow on the side of the litotripsy. For a majority of patients, this alteration is transient. HYPERTENSION: In a few cases, abrupt onset of transient hypertension has been reported in clear relation with a compressive perirenal hematoma. The causal effect of ESWL on late occurrence of permanent hypertension is however still uncertain, probably because of the difficulty to show that this occurrence is not related to the older age of the patient alone. The FDA sponsored multicentric study begun in 1993 should solve this issue in the future. PATIENTS AT RISK: Recent articles suggest that altered renal function prior to ESWL would predict late occurrence of hypertension and worsening of renal failure. Furthermore, age and the resistance index of arcuate or interlobular renal arteries (measured by Doppler) could help to screen the patients at risk of developing hypertension. Practical attitude: In practice, renal function and blood pressure should be carefully monitored in patients aged over 60 and/or who have a serum creatinine > 300 mumol/l.

[Primary hyperparathyroidism. Lack of effect of cimetidine on plasma levels of parathyroid hormone and calcium]. / Hyperparathyroïdie primitive. Absence d'effet de la cimétidine sur les taux plasmatiques de parathormone et de calcium.

Because of the contradictory results formerly published as regards the effect of cimetidine in primary hyperparathyroidism, we have studied the effect of cimetidine at the daily dose of 1200 mg in 14 cases of primary hyperparathyroidism. The diagnosis was ascertained in all cases by the coexistence of an otherwise unexplained hypercalcemia and of a concomitantly elevated plasma concentration of immunoreactive parathyroid hormone (PiPTH) measured by 2 different antibodies and confirmed in 10 cases by surgical neck exploration. In 5 cases with severe hypercalcemia (greater than 12.0 mg/l) cimetidine was discontinued after 5 days because of its lack of effect on both plasma concentrations of calcium and PiPTH, and the patients were successfully operated. In 8 cases with milder hypercalcemia, cimetidine was given for 1.5-6 months. There was no significant change in both plasma concentrations of calcium (PCa) and PiPTH but a regression analysis showed that PCa was negatively correlated to time with a correlation coefficient which would have become significant if the follow-up had been 9 months. In the last patient severe hypercalcemia was controlled by simultaneous administration of phosphate, indomethacin and cimetidine without concomitant decrease of PiPTH; and 6 weeks after cimetidine discontinuation no significant increase of PCa and PiPTH occurred. These data show that cimetidine has no clinically therapeutic value in primary hyperparathyroidism.

[Long-term stability of bone mineral density in patients with renal transplant treated with cyclosporine and low doses of corticoids. Protective role of cyclosporine?]. / Stabilité à long terme de la densité minérale osseuse des transplantés rénaux sous ciclosporine et faibles doses de corticoïdes. Rôle protecteur de la ciclosporine?

OBJECTIVES: Cyclosporine has been thought to have a deleterious effect on bone in transplant recipients because of high turnover osteopenia observed in humans after transplantation. However, varying confounding factors such as renal and parathyroid function, cumulative steroid doses and previous exposure to aluminium, also play a role and hinder interpretation of the cyclosporine effect on bone mineral density (BMD). PATIENTS AND METHODS: A 2-year prospective study was conducted to measure BMD starting 3 months after transplantation and bone remodeling markers from the first post-transplantation day in 52 kidney recipients with no prior exposure to aluminum. None of the patients experienced rejection and at 3 months all had good stable renal function (serum creatinine 137 mumol/l) and mildly elevated parathyroid hormone levels (1.5 times the upper limit of normal). All patients were given the same low dose steroid treatment (10 mg/day) and at 6 months cyclosporine was decreased from 7 to 4.8 mg/kg/day. RESULTS: BMD measured by double energy X-ray absorptiometry, (DEXA) and expressed in Z score, was moderately decreased at 3 months for the vertebrae (-1.40), the femoral neck (-1.34) and the ultradistal radius (-0.95) which have predominantly cancellous bone and was significantly less decreased (p < 0.05) for the lower third of the radius (-0.6) which is mainly cortical bone. BMD measurements were comparable at 6, 12 and 24 months. When measured by axial computerized tomography (ACT) BMD of the vertebrae showed a non-significant increase of Z score from -1.37 to -1.19 at 2 years. Bone remodeling markers was observed up to month 6 (from month 3 for osteocalcine and from month 1 for total and bone alkaline phosphatase and urinary pyridinoline), then returned to baseline levels at 2 years in parallel with decreased cyclosporine dosage. The increase of vertebral BMD measured by ACT at 1 year was correlated both to cyclosporine dose at 1 year and to bone alkaline phosphatase at 6 months. CONCLUSION: Our data confirm the presence of moderate osteopenia 3 months after transplantation, predominantly in trabecular bone, logically linked to the initial high doses of corticosteroids. The long-term stability of BMD measured by DEXA and the correlation of vertebral BMD increase measured by ACT with cyclosporine dose and bone alkaline phosphate suggest that cyclosporine had a beneficial immunosuppressor effect by stimulating bone remodeling and thus counterbalancing the suppressive effect of corticosteroids.

[Is ligation of the remaining native ureter at the time of renal transplantation always harmless?]. / La ligature de l'uretère propre restant, lors des transplantations rénales, est-elle toujours anodine?

Three cases of nephrectomy after transplantation with uretero-ureteral anastomosis are presented: this anastomosis in transplantation looks to be anodyne when the transplant keeps normal function. Complications become when appears a degradation of the renal function.

[Value of nephron preservation in conservative surgery of renal tumors]. / Intérêt de la préservation néphronique dans la chirurgie conservatrice des tumeurs rénales.

The increasing use of abdominal ultrasonography and computed tomography results in the increasingly early diagnosis of subclinical renal tumours. These asymptomatic tumours can sometimes be treated conservatively. This technique raises the problem of the multifocal nature of renal tumours In order to assess the real benefit of nephron-sparing surgery in relation to the risk of recurrence, this study evaluates the repercussions of exclusive tumour resection on the nephron number. From 1990 to 1995, 28 patients underwent partial nephrectomy for suspected renal cell carcinoma. Computed tomography was use to estimate the volume and therefore the weight of the kidney and the tumour: weight (g) = volume (mL) = length x width x height/2. The mean age of the patients was 59.1 years. The contralateral kidney was normal in 20 patients (group 1) and the tumour affected a solitary kidney in 8 patients (group 2). The initial serum creatinine level was normal (between 78 and 96) in all patients. The mean weight of the tumour was 16.1 g (13.6 g for group 1 and 22.3 g for group 2), and corresponded to 3.84% of the total kidney weight in group 1 and 9.73% in group 2. 1,400,000 nephrons were preserved in group 1 versus 900,000 nephrons in group 2, equivalent to a glomerular filtration rate of 89 mL/min and 58 mL/min, respectively. Partial nephrectomy therefore constitutes a real nephron-sparing technique. It allows sparing of a sufficient number of nephrons to ensure normal renal function and, most importantly, allows the possibility of subsequent partial surgery in view of the potential risk of multifocal tumours.

[Emphysematous pyelonephritis. Apropos of a case]. / La pyélonéphrite emphysémateuse. A propos d'un cas.

Emphysematous pyelonephritis is a rare form of pyelonephritis that carries a very poor prognosis. This article reports a review of the literature on this condition and describes the clinical and roentgenographic criteria for diagnosis. Diagnosis rests on the presence of clinical manifestations of pyelonephritis with intrarenal air-filled images on the roentgenograms. Both the author's personal experience and the data from the literature confirm the need for urgent treatment combining antimicrobial agents effective against Escherichia coli, the most common causative agent, and surgery, which usually consists in a nephrectomy.

[Hypercalcemia in blood diseases and cancers]. / Hypercalcémies des hémopathies et des cancers.

The clinical classification of malignant hypercalcaemias according to the presence or absence of bone lesions no longer corresponds to the physiopathology of these hypercalcaemias as it is known today. Both focal osteolysis and humoral hypercalcaemia involve a number of substances, such as prostaglandins, cytokines, growth factors, PTH-rp and calcitriol, the action of which is neither specific nor single. A knowledge of their role in the pathogenesis of hypercalcaemia should lead to the development of antagonists for therapeutic purpose and to a better understanding of their individual physiological effects, since some of these mediators are present in non-tumoral tissues. In humoral hypercalcaemia, PTH-rp seems to play a major role on kidneys and bones.