[APC resistance due to factor V Leiden mutation presenting as acute hemorrhagic jejunal infarction--case report]. / Akuter hämorrhagischer Jejunuminfarkt als Erstmanifestation einer APC-Resistenz bei Faktor-V-Leiden-Mutation--ein Fallbericht.

We report on a 43-year-old patient presenting to the emergency department with acute abdominal pain the source of which turned out to be acute hemorrhagic jejunal infarction due to portal and mesenteric vein occlusion with no apparent cause. In spite of a lacking history of hereditary thrombophilic risk factors, further diagnostic procedures revealed heterozygous factor V Leiden mutation. Diagnosis, therapy and clinical course are described. An overview on acute mesenteric venous occlusion with special reference to genetically determined thrombophilic disorders is given.

Differential effects of cyclosporine and tacrolimus on mycophenolate pharmacokinetics in patients with impaired kidney function.

In a single-center prospective randomized controlled study, the impact of calcineurin inhibitor (CNI) reduction or withdrawal on the pharmacokinetics of mycophenolic acid (MPA) was studied in a group of renal transplant recipients with impaired renal function. Mycophenolate mofetil (MMF) was added to a baseline regimen of prednisolone and CNI. Afterwards the patients were randomized into "CNI withdrawal" and "CNI continuation" groups. The dosage of CNIs, cyclosporine or tacrolimus, was gradually reduced and withdrawn within 6 weeks from patients in the withdrawal group. The continuation group was maintained on therapy with CNI, MMF, and steroids. These regimens were maintained until the ninth month. In contrast to the withdrawal of tacrolimus, which has no significant effect on MPA pharmacokinetics, cyclosporine withdrawal was associated with a significant increase in the trough levels and areas under the curve of MPA. Serum creatinine and urine albumine levels stabilized on average after CNI withdrawal in this population. The results are consistent with the hypothesis that cyclosporine attenuates the enterohepatic recirculation of MPA. The withdrawal of CNI has a positive effect on renal function in chronic allograft dysfunction.

Switching immunosuppression from cyclosporine to tacrolimus improves long-term kidney function: a 6-year study.

To improve long-term kidney graft function, acute graft rejection, hyperlipidemia, hypertension, and toxic influences must be avoided because they may contribute to chronic allograft nephropathy. Many studies have demonstrated greater efficacy and tolerability of tacrolimus compared with cyclosporine with regard to these conditions. Our study investigated whether 30 patients with deteriorating renal function benefitted from conversion to tacrolimus based upon a retrospective analysis using data recorded from 3 years before to 3 years after conversion. Renal function (GFR) deteriorated progressively under cyclosporine (creatinine: baseline 1.5 mg/dL; delta(Cyc) = +1.4 mg/dL within 3 years; GFR: delta(Cyc) = -35 mL/min within 3 years). After switching to tacrolimus, kidney function stabilized and even improved (creatinine: baseline after switching 2.9 mg/dL; delta(Tac) = -0.7 mg/dL; GFR: delta(Tac) = 14 mL/min). Conversion from cyclosporine to tacrolimus is recommended for patients with a kidney transplant in which there has been a progressive decrease in renal function. It may lead to stabilization of or even improvement in transplant function.

Cyclosporine and tacrolimus: influence on cardiovascular risk factors.

After allogenic transplantations, a dramatic increase in the development of arteriosclerotic plaques can be observed, which might be due to metabolic alterations, changes in the transplant organ, or the immunosuppression regimen. Many studies have demonstrated beneficial effects of tacrolimus compared with cyclosporine with regard to these conditions. These results have suggested that conversion to tacrolimus from cyclosporine is advantageous. Our study investigated whether patients with deteriorating renal function profit from this conversion. Thirty renal transplant patients were studied retrospectively, using data recorded from 3 years before to 3 years after conversion from cyclosporine to tacrolimus. While renal function (GFR) deteriorated progressively under cyclosporine, it stabilized and even improved under tacrolimus (creatinine: DeltaCyc = +1.4 mg/d; DeltaTac = -0.7 mg/dL; GFR: DeltaCyc = -35 mL/min; DeltaTac = 14 mL/min). In addition, uric acid levels (7.0 mg/dL vs 6.4 mg/dL, P < .05) and cholesterol levels (258 mg/dL vs 225 mg/dL, P < .05) were both significantly lower under tacrolimus. Conversion from cyclosporine to tacrolimus is recommended for kidney transplant patients in whom there has been a progressive fall in renal function. It leads to stabilization or even improvement of transplant function and a reduction in cardiovascular risk factors.

Conversion from cyclosporine to tacrolimus after renal transplantation improves cardiovascular risk factors.

BACKGROUND: It is vital that after, renal transplantation, immunosuppression is efficacious and causes few complications. It is especially important that hyperlipidaemia, hypertension and toxic influences should be avoided because these conditions can reduce patient and transplant survival. Many studies have demonstrated beneficial effects of tacrolimus in comparison with cyclosporine with regard to these conditions. These results have suggested that a conversion to tacrolimus from cyclosporine is advantageous. Our study investigated whether patients with deteriorating renal functions can profit from this conversion. METHODS: Thirty patients with a renal transplant were studied retrospectively, using data recorded from 3 years before to 3 years after conversion from cyclosporine to tacrolimus. RESULTS: While renal function (glomerular filtration rate [GFR]) deteriorated progressively under cyclosporine, it stabilised and even improved under tacrolimus (creatinine: Delta(Cyc)=+1.4 mg/d; Delta(Tac=)-0.7 mg/dl; GFR: Delta(Cyc)=-35 ml/min; Delta(Tac)=14 ml/min). In addition, uric acid level (7.0 vs. 6.4 mg/dl, p<0.05) and cholesterol level (258 vs. 225 mg/dl, p<0.05) were both significantly lower under tacrolimus. CONCLUSION: Conversion from cyclosporine to tacrolimus is recommended for patients with a kidney transplant, in which there has been a progressive fall in renal function. It leads to stabilisation or even improvement of transplant function and a reduction in cardiovascular risk factors.

Effect of parathyroid hormone levels on carotid intima-media thickness after renal transplantation.

BACKGROUND: The present study aimed to investigate the intact parathyroid hormone (iPTH)-dependent evolution of common carotid intima-media thickness (CC IMT) in renal transplant recipients (RTR) within a 12-month follow-up, ie, before (E0) and 3 months (E3), 6 months (E6), and 12 months after renal transplantation (RTX). METHODS: A total of 55 normotensive patients, aged 47 +/- 1.7 years, underwent a RTX. The graft function was stable (clearanceCockroft >60 mL/min and S-creatinine <2.5 mg/dL) in all patients throughout the follow-up. RESULTS: In 67% of the RTR, the iPTH levels were classified as high at E0 (E6: 63%; E6: 49%; E12: 67%). The plasma iPTH levels decreased after RTX (P < .01). The arterial blood pressure remained stable. The CC IMT was positively and independently correlated with age (P < .01), gender (P < .01), and iPTH levels (P < .01). CONCLUSIONS: Normalization of iPTH levels is associated with a significant intima-media thickness (IMT) reduction. The increased IMT in renal transplant recipients may contribute to the high cardiovascular morbidity and mortality in patients with end-stage renal failure.

Influence of age on the prognosis of renal transplant recipients.

With aging, morphologic organ changes due to arteriosclerosis, hypertension, or diabetes increase, and renal transplantation tends to become less successful. We analyzed the outcome of transplantation in 123 recipients who underwent renal transplantation between January 1988 and December 1989. We assessed patient and graft survival after 1, 5, and 6 years as well as mortality and transplant failure and the incidence of rejections. We compared the results of patients aged under 60 years (group 1, n = 60) with the findings of patients aged over 60 years (group 2, n = 63). Immunosuppression was with cyclosporin A and prednisolone without exception. In patients under the age of 60, the overall patient survival at 1, 5, and 6 years was 97, 95, and 90% and was significantly compromised in recipients over the age of 60 (92, 80, and 75%). The 1-, 5- and 6-year graft survival rates were 92, 90, and 90% in recipients aged over 60 years and 88, 82, and 79% in recipients under the age of 60 years. The incidence of rejection was significantly higher in recipients under the age of 60. Patient mortality was mainly due to cardiovascular complications and transplant failure mainly related to transplant thrombosis. In older patients, renal transplantation is thought to be an option of survival rate improvement in comparison with hemodialysis. The incidence of transplant rejection is significantly lower, and this indicates a promising result regarding the long-term prognosis. As cardiovascular complications present as the main mortality factors of both transplant and patient, the prognosis is considered to be highly dependent on screening and treatment of these risk factors.

Impact of estradiol blood concentrations on skin capillary Laser Doppler flow in premenopausal women.

OBJECTIVE AND METHOD: Estradiols are known to prevent cardiovascular diseases, but the underlying mechanisms remain unclear. We assessed the finger skin capillary blood flow in 20 premenopausal women with oral contraception noninvasively by Laser Doppler flowmetry (LDF). Blood flow was registered both under basal conditions and after 2 min of arterial occlusion. Furthermore, the combination with a beat-to-beat online finger blood pressure monitor allowed the calculation of the regional peripheral resistance (RPR). All measurements were performed in the menstrual phase. LDF and RPR were correlated to the estradiol whole blood levels. RESULTS: Both baseline (r(2)=0.826; P<0.01) and vasodilation (r(2)=0.747; P<0.01) blood flux were significantly correlated to the corresponding estradiol concentrations. A multiple stepwise regression analysis (with age, height, weight, duration of oral contraception, nicotine pack years and estradiol levels in the equation) showed positive correlations between estradiol levels and (a) baseline (P<0.05) or (b) vasodilation (P<0.05) Laser Doppler flux or (c) time to reach the peak flux (r(2)=0.31; P<0.05). Furthermore, the minimal local vascular resistance was negatively correlated to the estradiol levels (r(2)=0.45; P<0.05). CONCLUSION: The study provides evidence that both the baseline and the vasodilation capillary blood flux in women in the menstrual phase depend on the estradiol whole blood levels. Furthermore, the local vascular resistance shows a negative correlation to the hormonal state. Functional or structural alterations of the microvasculature may therefore contribute to the estradiol-associated cardiovascular protection.

Comparison of quinapril versus atenolol: effects on blood pressure and cardiac mass after renal transplantation.

Based on epidemiologic facts on elevated cardiovascular mortality in renal allograft recipients, an echocardiographic 2-year follow-up in hypertensive renal allograft recipients was conducted. This study provides evidence that, in contrast to atenolol, quinapril, independent of blood pressure reduction, reduces left ventricular hypertrophy and improves left ventricular diastolic function in this population.

[Variability of blood pressure and baroreceptor function; clinical and scientific relevance]. / Blutdruckvariabilität und Barorezeptorfunktion. Klinische und wissenschaftliche Relevanz.

The human arterial blood pressure shows not only exogenic alterations, but also spontaneous fluctuations. This blood pressure variability has both scientific and clinical relevance. A well-known phenomenon is the so-called "white coat hypertension" which may severely affect diagnosis and therapy of essential hypertension. Furthermore, several studies have provided evidence that the degree of end-organ damage in hypertensive patients is closely related to the circadian blood pressure variability. Therefore, it is tempting to suggest that an optimal antihypertensive treatment should take an improvement of the blood pressure variability into consideration. Among other mechanisms modulating the arterial blood pressure, the baroreflex function has to be mentioned. Diseases like chronic renal failure, treatment with drugs like ciclosporine A and also smoking have been shown to reduce the baroreflex sensitivity. As the baroreflex sensitivity mainly reflects interactions between the blood pressure variability on the one hand and the heart rate variability on the other hand, it is not surprising that also a reduced baroreflex function is an independent cardiovascular risk factor.