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Biomedical subjects

A Voiculescu

Publications and source records attributed to A Voiculescu.

At least 19 recordsLinked to original sources
PubMed2007

Intravenous iloprost: a new therapeutic option for patients with post-transplant distal limb syndrome (PTDLS).

The purpose of this study was to investigate the application of intravenous iloprost as a novel therapy for the treatment of post-transplant distal limb syndrome (PTDLS). PTDLS is a benign but disabling complication in the first year after renal transplantation. It is characterized by bilateral, often incapacitating pain in the feet and or knees on motion and a significant rise in alkaline phosphatase levels on laboratory evaluation. On MRI, bone marrow edema of the affected bone regions can be demonstrated. PTDLS differs from steroid induced osteonecrosis of the hip in terms of localization, an average cumulative steroid dosage within expected limits, and a benign outcome, as PTDLS does not progress to overt cell necrosis. From August 2003 to April 2005 we treated 10 patients with MRI-proven diagnosis of PTDLS following a standardized regimen of intravenous iloprost over 5 days. Iloprost led to prompt pain relief measured on a visual analogous scale (VAS) ranging from 1 to 10 (5.6 +/- 1.5 before vs. 2.1 +/- 1.3 after treatment, p = 0.0004). PTDLS represents a benign but disabling complication following renal transplantation. Intravenous iloprost might be a promising therapeutic concept leading to a quick relief of symptoms without relevant side effects.

Adult↗
PubMed2006

Renovascular disease: a review of diagnostic and therapeutic procedures.

The clinical importance of renovascular disease, atherosclerotic or of other origin, arises from the fact, that renal artery stenosis (RAS), if hemodynamically significant (> 70% diameter reduction), induces arterial hypertension, renal insufficiency or both. The prevalence of RAS rises with increasing age and with the presence of atherosclerosis of the aorta, carotid, coronary and peripheral arteries. Typical clinical symptoms, as uncontrolled hypertension or renal dysfunction in the absence of pathological urinary findings, are helpful to select patients for further screening methods: We see a prominent role of color duplex sonography as a screening procedure. Intra-arterial angiography remains gold standard for the diagnosis of RAS. The major problem in daily clinical practice is the differentiation between patients in which hypertension and kidney function can be improved or normalized by removal of RAS and those with ''fixed'' hypertension and irreversible kidney dysfunction and therefore to decide if it is worth while to perform invasive treatment as angioplasty or surgery. In this setting, the proof of hemodynamic significance is essential and is indicated especially when the stenosis has a diameter reduction of < 50-70% only. Methods proving a critical stenosis are intra-arterial measurement of the pressure gradient, measurement of differential renal vein renin and duplex sonography. In addition, predictors of treatment outcome should be considered. Studies analyzing if patients improve with blood pressure and kidney function after removal of RAS have shown that high grade stenosis and/or very high blood pressure indicate a good outcome. Further prognostic factors are the absence of parenchymal disease and/or positive functional test. In the presence of a critical stenosis in a patient with a clear clinical problem with hypertension and/or renal dysfunction a positive effect of invasive treatment seems warranted despite the risks that must be considered as well in angioplasty as in surgery. The selection for the type of invasive treatment requires a clarification of the treatment goals in the individual patient, the evaluation of the morphology and localization of the stenosis as the presence of other vascular disease (aortic aneurysm, peripheral artery disease etc.) and the assessment of the risk according to the type of intervention.

Decision Trees↗
PubMed2003

Successful treatment of renovascular hypertension has no effect on insulin sensitivity.

BACKGROUND: The association of insulin resistance (IR) and essential hypertension is well known, but a causal relationship has not been proven. Patients with secondary hypertension as a result of renal artery stenosis (RAS) usually do not reveal IR, but no study has addressed the effect of blood pressure reduction after successful treatment of RAS on insulin sensitivity and glucose effectiveness. PATIENTS AND METHODS: The insulin sensitivity index (SI) and glucose effectiveness (SG) were measured before and after successful intervention of an angiographically proven significant RAS in 18 out of 23 patients (eight males/10 females; mean age 51.5 +/- 13.1 years) in which improvement/cure of arterial hypertension was achieved. After a mean of 10.7 months, patients were reevaluated for 24-h blood-pressure measurement, kidney function, adrenaline, noradrenaline, plasma-renin-activity (PRA), aldosterone, atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP), and glucose metabolism parameters such as basal insulin, glucose disappearance constant (K-value), SI and SG. For calculation of SI and SG, insulin and glucose data from the modified frequent sampling intravenous glucose tolerance test (FSIGT) were submitted to the MINMOD program. RESULTS: After intervention, systolic 24-h blood pressure had decreased from 156.1 +/- 16.4 mmHg to 139.9 +/- 15.1 mmHg, and diastolic 24-h blood pressure from 97.1 +/- 14.7 mmHg to 87.3 +/- 13.4 mmHg. No significant change in SI (before 4.3 +/- 2.0, after 4.8 +/- 2.0 min(-1) per microU mL(-1)) or SG (before 1.55 +/- 0.42x10(-2) min(-1), after 1.8 +/- 0.48x10(-2) min(-1)) was observed. Aldosterone decreased from 246.7 +/- 180.7 to 115 +/- 61.4 (P=0.009) as PRA decreased from 12.4 +/- 11.4 to 4.2 +/- 7.6 ng mL h(-1) (P=0.01). Creatinine clearance, and adrenaline and noradrenaline levels as well as ANP and cGMP did not change after treatment for RAS. Subsequent to the definition of IR (SI < or =3.2x10(-4) min(-1) per microU mL(-1)) some differences among these two subgroups (SI < or =3.2, or SI>3.2) could be found. Patients with IR (n=8) were characterized by a higher body mass index (BMI), higher basal insulin values and significantly lower cGMP values. Only the group without IR (n=10) developed significant improvement of systolic blood pressure. CONCLUSION: We conclude that blood pressure reduction by treatment of RAS does not alter insulin action and that there is no link between the circulating concentrations of renin/aldosterone and glucose metabolism in renovascular hypertension (RVH). The results do not support the hypothesis of a direct link between blood pressure in RVH and the individual state of insulin sensitivity. However, patients with a normal SI are more likely to experience an almost normalization of arterial blood pressure after treatment for RAS.

Adult↗
PubMed2003

Hemodynamically relevant hematuria several months after biopsy of a kidney graft: an unusual cause.

We report the case of a 52-year-old female patient, who after a complicated living donor kidney transplantation, underwent kidney biopsy for suspected rejection. Duplex scanning revealed a small, asymptomatic arteriovenous (AV) fistula which was assessed as being hemodynamically unimportant. During follow-up, several urinary tract infections occurred and recurrent short episodes of hematuria were attributed to cystitis, urethritis and urosepsis. Eight months later, the patient developed suddenly massive hematuria, tamponade of the urinary bladder and hemorrhagic shock as well as urosepsis. Duplex sonography showed a massive pseudoaneurysm in addition to the AV fistula. Arteriography confirmed the Duplex sonographic findings and embolization was performed after treatment of concomitant urosepsis. The fistula was closed completely and bleeding ceased. Although AV fistulas are rare complications of kidney biopsies and in most cases they remain asymptomatic, life-threatening hematuria can present several months after a biopsy due to the development of a pseudoaneurysm. Concomitant infectious complications of the urinary tract, bleeding disorders and other factors can be misleading during the assessment of the cause of gross hematuria. Regular Duplex sonographic follow-up examinations in patients with AV fistulas are advisable.

Aneurysm, False↗
PubMed2002

[Aortoiliac reconstruction after kidney transplantation. Strategies to avoid ischemic damage of the transplant].

INTRODUCTION: The rising life expectancy of patients undergoing kidney transplantation and the improvement in the function rate of the allografts have led to an increasing number of patients suffering from arteriosclerosis-related diseases of the aortoiliac arteries. In these particular cases, an interruption of the blood supply of the allograft is always necessary for operative repair of the aortic and iliac arteries. This means a high risk of ischemic damage to the transplanted kidney. PATIENTS AND METHODS: Between 1987 and 2000, 1,076 kidney transplantations were performed in our department. During this time, 14 reconstructive operations of the aortoiliac arteries were performed in 12 patients (6 women, 6 men, average age 55.2 (45-71) years). Operations were indicated in patients suffering from occlusive disease with imminent extremity or allograft loss, and symptomatic or asymptomatic aneurysms with a maximum diameter of more than 4 cm. In patients presenting with thoracoabdominal (1) and abdominal aortic aneurysms (3), protection of the transplanted kidney was performed by axilloiliac or axillofemoral bypass. Hypothermic flush-perfusion of the allograft containing PGE1 and heparin was performed in seven of nine operations for occlusive disease. RESULTS: None of the patients presented with a permanent decrease in kidney function, six patients showed temporary creatinine elevation, and in nine patients creatinine levels at discharge were lower than they were preoperatively. None of the patients died. CONCLUSION: Reviewing all reported methods of allograft protection, we recommend a three-step strategy including sequential clamp technique (ischemia < 30 min.), hypothermic flush-perfusion (ischemia < or = 60 min.), and temporary axilloiliac/femoral shunt (ischemia > 60 min), depending on the expected renal ischemia time.

Aged↗
PubMed2001

Systemic mycophenolate mofetil in comparison with systemic cyclosporin A in high-risk keratoplasty patients: 3 years' results of a randomized prospective clinical trial.

BACKGROUND: With the use of systemic cyclosporin A (CsA), graft prognosis after high-risk penetrating keratoplasty has improved considerably. However, the application of CsA is limited owing to a variety of severe side effects. In this prospectively randomized study mycophenolate mofetil (MMF), a safe and efficient immunosuppressive medication after renal transplantation, was compared with CsA after high-risk penetrating keratoplasty. METHODS: Twenty-nine high-risk keratoplasty patients were treated with MMF 2x 1 g daily; another 27 patients received CsA, aiming at blood trough levels of 120-150 ng/ml. Systemic immunosuppression was scheduled for 6 months. In both groups oral corticosteroids (fluocortolone 1 mg/kg) were administered for 3 weeks postoperatively. RESULTS: During the first year after operation, no graft failure was recorded. Two years postoperatively 92%/82% and 3 years postoperatively 74%/69% of grafts were clear in the MMF and CsA group, respectively (Kaplan Meier P=0.33, logrank test). In total, two graft failures were recorded in the MMF group and four in the CsA group. Three years postoperatively 53% of the grafts were rejection-free in the MMF group and 73% in the CsA group (Kaplan Meier P=0.46, log-rank test). Eight endothelial immune reactions were observed in the MMF group (three under systemic immunosuppression/five thereafter; six mild/two severe) and five in the CsA group (three under systemic immunosuppression/two thereafter; three mild/two severe). Side effects occurred in six patients under MMF and 11 under CsA. CONCLUSIONS: Concerning efficacy, no statistically significant difference between systemic MMF and systemic CsA administered for 6 months after high-risk penetrating keratoplasty could be shown. Systemic MMF was proven to be at least as safe as CsA. The main mechanism in improving graft survival is a shift from severe to milder endothelial immune reactions, as already demonstrated for CsA. Thus, MMF may become an alternative to CsA for immunosuppression after penetrating high-risk keratoplasty. About 2 years postoperatively, pharmacologically induced relative immunological tolerance slowly decreases. Therefore, long-term administration of systemic MMF should be evaluated in further studies.

Adolescent↗
PubMed2001

Eurotransplant Senior Program 'old for old': results from 10 patients.

More frequently there is the need for renal transplantation of older patients. Against the background of an increasing number of old donors and recipients, Eurotransplant Leiden started the Eurotransplant Senior Program (ESP) 'old for old' in 1999. The ESP works with donors and recipients both over 65 yr. The kidneys are transplanted with short cold ischaemia time regardless of the human leukocyte antigen (HLA) compatibility. Compatibility of blood groups, negative crossmatch and less than 5% cytotoxic antibodies are required. First experiences from 10 patients at Heinrich Heine University hospital are reported here. The course of 10 transplanted patients is described from January 1999 until November 1999 (28.4+/-15.8 wk). Age of donor and recipient, cause of dialysis and concomitant diseases from recipients, function of the transplanted kidney and complications are analysed. Immunosuppression consisted initially of cyclosporin A, mycophenolic acid and steroids. The results of these 10 patients were compared to 14 patients who were transplanted according to the ordinary Eurotransplant criteria (Eurotransplant Kidney Allocation System) in the same period of time. Kidneys from six donors (70.5+/-3.3 yr) were transplanted to 10 different recipients (66.9+/-2.2 yr). The control group consisted of 14 patients (47.6+/-14.4 yr) who received kidneys from 14 donors (48.3+/-10.1 yr). One double kidney transplantation was performed in the senior group, i.e. two kidneys from a marginal donor were transplanted to one recipient ('two in one'). In the ESP group, cold ischaemia time was reduced by 5 h and mean of HLA mismatches was more than doubled. Mean length of hospitalisation of ESP and control groups was 47.2+/-28.2 and 34.2+/-11.6 d, respectively. Intraoperatively, no complications were seen, post-operative care was performed on a normal ward. ESP patients suffered more often from delayed graft function, which led to further need for haemodialysis for 11.2 d. Finally, 9 of 10 patients acquired a satisfactory renal graft function. A total of 13 biopsies were performed in eight cases. Altogether seven acute rejections in 6 patients were found (four interstitial, one vascular, one interstitial+vascular, one clinical). The 9 patients with sufficient renal graft function were discharged with a mean serum creatinine level of 2.3+/-0.5 mg/dL (control: 1.9+/-0.8 mg/dL). Comparing these 10 recipients to a control group consisting of 14 patients, the results are comparable and encouraging. In conclusion, the short-term results of the ESP are promising. Nevertheless, the post-operative care requires more attention due to several complications. Though the HLA compatibility was not considered, all rejections were coped with effectively. Quality of life was improved.

Age Factors↗
PubMed2001

[Highly active antiviral and immunosuppressive combination therapy with acyclovir and mycophenolate mofetil following keratoplasty in patients with herpetic eye disease].

BACKGROUND: Herpes simplex virus (HSV) infection is the most common cause of corneal blindness in developed countries. Penetrating keratoplasty is the only therapeutic option for visual rehabilitation in patients with severely scarred corneas. Recurrence of the underlying disease and allograft rejection (AR) are the common causes of graft failure. Systemic immuno-suppression with cyclosporin A is contraindicated due to the risk of HSV recurrence. The potent immunosuppressive properties of mycophenolate mofetil (MMF) have already been shown clinically. By reducing the intracellular guanosid-pool MMF inhibits the proliferation of lymphocytes. As these quanosin-nucleosides also act as competing substrates to acyclovir at the viral DNA-polymerase, a synergistic effect of MMF and acyclovir might be expected. The aim of this study was to evalute the efficacy and safety of a double-drug regimen with MMF and acyclovir in the prevention of acute allograft rejection and HSV recurrence following corneal transplantation. METHODS: Patients following penetrating keratoplasty due to herpetic eye disease have been treated with MMF 1 g twice dialy and acyclovir 5 x 200 mg/day for one year. Primary efficacy variables have been the number of acute AR and recurrence of herpetic disease per patient and time. The number of adverse events has been documented for safety analysis. RESULTS: Fifteen patients have been enrolled. The average follow up period was 9.1 (+/- 5.2) months. No graft opacifications have been seen. With two AR and no recurrence of herpetic disease the efficacy ofthis therapeutic regimen was supperior compared with historical control groups. CONCLUSION: In this first study on the efficacy and safety of a double drum regimen with acyclovir and MMF for the control of acute corneal AR and HSV-recurrenct following keratoplasty in patients with herpetic eye disease, the combination therapy has been shown to be a safe and highly efficient protocol for graft protection.

Acyclovir↗
PubMed2001

Noninvasive investigation for renal artery stenosis: contrast-enhanced magnetic resonance angiography and color Doppler sonography as compared to digital subtraction angiography.

INTRODUCTION: The question about the most appropriate non-invasive method for detecting a renal artery stenosis (RAS) when comparing contrast enhanced magnetic resonance angiography (MRA) and color Doppler sonography (CDS) is still under discussion. Therefore we conducted a prospective study in order to evaluate both methods as compared to digital subtraction angiography (DSA). PATIENTS/METHODS: Thirtysix consecutive patients (53,9 +/- 13,7 years) with suspected RAS were investigated. MRA was performed using gadolinium for contrast enhancement. CDS was performed using a 2.5 and 3,5 MHz transducer. A peak systolic velocity (Vmax) >200 cm/sec within renal arteries and/or a side to side difference of the resistive index (RI) of >0,05 were used to discriminate stenosis. A diameter reduction of > or = 60% by DSA was considered a stenosis relevant to the patient. RESULTS: Sixty-eight main renal arteries and 9 accessory vessels were detected by DSA. Twenty main and 3 accessory arteries were found to be stenosed > or = 60%, while 4 main and 1 accessory artery presented with occlusion. MRA detected 70 renal vessels (65 main and 5 accessory arteries). Twenty-one stenosed arteries and 4 occluded vessels were correctly diagnosed by MRA. With CDS 68 renal vessels (62 main and 6 accessory arteries) could be visual- ized out of which 21 stenoses were diagnosed because of increased Vmax and 6 stenoses were detected because of a side to side difference of RI. For main renal arteries sensitivities and specificities were 96% and 86% for MRA and 96% and 89% for CDS. CONCLUSIONS: MRA and CDS are both comparable methods for detection of a renal artery stenosis > or = 60%. Despite several limitations, CDS can at the moment still be favored as a screening method.

Adult↗
PubMed2001

Assessment of radiocontrast media induced renal vasoconstriction by color coded duplex sonography.

INTRODUCTION: Changes in renal hemodynamics are suspected to be one of the major pathogenetic correlates in radiocontrast media-induced nephrotoxicity. We investigated whether color-coded duplex sonography is an appropriate method to document changes in intrarenal vascular resistance, after intravenous injection of the low-osmolar contrast material lopamidol. METHODS: Intrarenal arterial doppler wave forms were analyzed every minute after intravenous injection of 100 mL lopamidol in 10 patients during a voiding cystourogram-procedure. The Resistive Index (RI) of each flow curve, reflecting intrarenal flow resistance, was calculated and compared to the mean of four RI measurements taken before contrast media application. RESULTS: One minute after injection of Iopamidol the RI remained unchanged compared to the baseline standard of 0.70. In measurements obtained 2, 3, 4, and 5 minutes after lopamidol injection a statistically significant rise was seen: (minute 2: 0.74, p < 0.001/minute 3: 0.75, p = 0.001/minute 4: 0.72, p =0.018/minute 5: 0.74, p = 0.031). During the further course, the resistive indices decreased progressively and showed no significant difference in comparison with the baseline standard value. CONCLUSION: Color coded duplex sonography is a simple method to detect changes in renal flow resistance after application of radiocontrast media. Based on our results, we believe that the analysis of intrarenal arterial doppler flow profiles constitutes an ideal method to investigate pathophysiologic mechanisms of radiocontrast media-induced nephrotoxicity, as well as pharmacological concepts in nephroprotectivity.

Contrast Media↗
PubMed2000

Effect of acute intravenous ace-inhibition on the intrarenal doppler flow characteristics in hypertensive patients with and without unilateral renal artery stenosis.

Assessment of intrarenal doppler signals is of particular importance in screening for renal artery stenosis. We studied the effect of acute ACE-inhibition (1,25 mg enalaprilate i.v.) on intrarenal resistive indices in 10 hypertensive patients with unilateral renal artery stenosis versus 10 patients with essential hypertension. Any changes limited to poststenotic vessels could possibly improve the diagnostic value of duplex sonography. After ACE-inhibition a significant fall of the intrarenal Resistive Index occurred in both patient groups. In cases of unilateral renal artery stenosis we saw a tendency to an increased side difference of the Resistive Index due to a greater fall on the poststenotic side. Therefore a clear advantage of duplex scanning after acute ACE-inhibition due to a limited effect of enalaprilate on poststenotic vessels was not found. The results suggest that the vascular resistance and not only the degree of renal artery stenosis is of significance for the characteristics of the doppler signal.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Post-transplant distal-limb bone-marrow oedema: MR imaging and therapeutic considerations.

BACKGROUND: In recent years a previously unrecognized pain syndrome of the distal lower limbs after organ transplantation has been noted. A relationship to cyclosporin A was suspected, but no clear aetiology and pathogenesis have been established. METHODS: During the last 30 months we diagnosed the pain syndrome in 10 patients after renal transplantation. We prospectively followed and evaluated the patients during their clinical courses and through pathological laboratory findings and magnetic resonance imaging (MRI). RESULTS: In all patients symptoms developed within 6 months of transplantation after otherwise uncomplicated clinical courses without graft rejection episodes. Impressive bone-marrow oedema on MRI as well as elevated serum alkaline phosphatase was seen in all patients, and often exceeded the duration of clinical symptoms. All patients were instructed to avoid stress to the extremities through immobility, and steroid doses were tapered down. Within 14 weeks, eight patients were free of symptoms. Two patients have not experienced remission after 3 and 4 months respectively. None of the patients developed signs of osteonecrosis. CONCLUSION: Post-transplant distal limb bone-marrow oedema presents with distinct clinical findings and signs of bone-marrow oedema on MRI. Proven standard treatment does not exist. In our experience the elevation of the extremities, the strict avoidance of physical strain, and a stepwise withdrawal of steroids facilitates progressive disappearance of symptoms. Long-term damage to the affected ostial structures has not been seen, in contrast to avascular femoral-head necrosis.

Adult↗
PubMed1999

[Mycophenolate mofetil after penetrating high risk keratoplasty. A pilot study].

AIM: Mycophenolate mofetil (MMF, CellCept) has become a successful part of the standard immunosuppression regimes after solid organ transplantation. It was the aim of this study to compare the efficacy and the safety of MMF after penetrating high-risk keratoplasty with our standard immunosuppression, i.e. systemic cyclosporin A (CSA), in a pilot study. PATIENTS AND METHODS: Sixteen patients after penetrating high-risk keratoplasty were randomized to be treated either with MMF or with CSA for six months postoperatively. MMF was administered in an oral dose of two times 1 g daily whereas the CSA dose varied according to the blood trough levels of 120-150 ng/ml (monoclonal TDx) between 100 and 500 mg daily. RESULTS: During this first follow-up period of 11.4 (5-18) months neither in the MMF- nor in the CSA-group irreversible graft failure was observed. One serious acute endothelial immune reaction was observed in the CSA-group after systemic immunomodulation had been tapered. It was treated successfully with systemic and topical corticosteroids. In one patient CSA-prophylaxis had to be stopped five months postoperatively because of elevated liver enzymes. Side-effects did not occur in the MMF-group. CONCLUSIONS: Up to now MMF has been evaluated to be as efficacious as CSA and safe. If these results are confirmed in the long run in this study MMF may become an armament to avoid immune reactions in high-risk penetrating keratoplasty patients who must not receive systemic CSA.

Cyclosporine↗
PubMed1999

Mycophenolate mofetil versus cyclosporin A in high risk keratoplasty patients: a prospectively randomised clinical trial.

BACKGROUND/AIMS: The requirement for an effective, minimally toxic immunosuppressive agent remains a major obstacle to performing high risk corneal transplantation. Although therapy with cyclosporin A (CSA) allows superior graft survival, its use is limited because of a wide range of side effects. Mycophenolate mofetil (MMF) has been shown to be a safe and effective immunosuppressive agent following renal transplantation. This prospective, randomised clinical trial was carried out to investigate the efficacy and safety of MMF in preventing corneal allograft rejection. METHODS: Recipients of corneal transplants who were at high risk for graft failure were randomly assigned to either CSA or MMF immunosuppressive therapy. CSA was given in doses to achieve whole blood trough levels of 120-150 ng/ml. MMF was given in a daily dose of 2 g. Both therapy groups additionally received oral corticosteroids (fluocortolone 1 mg/kg) which were tapered and discontinued within the first 3 postoperative weeks. Patients were monitored closely for evidence of corneal graft rejection and adverse side effects. Drug efficacy was measured, primarily, by the number of patients who experienced at least one episode of clinical graft rejection. Safety analysis focused on reported adverse side effects and laboratory measurements. RESULTS: 41 patients were enrolled in the study. There was no statistically significant difference between the two groups. 20 patients received CSA and 21 patients received MMF. Two patients in each group showed evidence of acute graft rejection which could be treated effectively by corticosteroids. All corneal grafts remained clear throughout the follow up. CONCLUSIONS: In this study it was shown that MMF is just as effective as CSA in preventing acute rejection following high risk corneal transplantation. Mycophenolate mofetil represents a promising alternative therapeutic option in patients who are at high risk for corneal graft failure.

Adult↗