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Biomedical subjects

G R Hetzel

Publications and source records attributed to G R Hetzel.

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↗
PubMed2002

Effects of candesartan and perindopril on renal function, TGF-beta1 plasma levels and excretion of prostaglandins in stable renal allograft recipients.

AIMS: Although on account of their nephroprotective effects, ACE inhibitors and angiotensin receptor antagonists appear to be advantageous for patients after renal transplantation, their use in these patients has been limited up to now. This is in part due to the risk of inducing a decrease in the glomerular filtration pressure gradient with subsequent impairment of allograft function. The aim of the present study was to investigate the effects of ACE inhibitors and angiotensin receptor antagonists on renal function, excretion of prostaglandins as a parameter of glomerular hemodynamics and TGF-beta1 plasma levels during an 8-week withdrawal phase in pretreated patients. PATIENTS AND METHODS: Sixteen patients with stable long-term allograft function undergoing therapy with candesartan (group 1) and 16 patients with stable long-term allograft function undergoing therapy with perindopril (group 2) were included in the study. Any signs of chronic allograft dysfunction were defined as exclusion criteria. Renal function, albuminuria, TGF-beta1 plasma levels as well as the excretion of thromboxane B2 and 6-keto-prostaglandin-F-1alpha were monitored during an 8-week withdrawal phase of the angiotensin receptor antagonist or ACE inhibitor, respectively. Normotension was maintained throughout the study period through adjustment of other anti-hypertensive drugs. RESULTS: Creatinine clearance as well as TGF-beta1 plasma levels and the excretion of prostaglandins remained unchanged after discontinuation of candesartan or perindopril. However, after withdrawal of the substances a significant increase in albuminuria was noted in both patient groups throughout the observation period. After 8 weeks, median albuminuria had increased by 63% in group 1 and by 163% in group 2. CONCLUSIONS: We were able to demonstrate that the use of ACE inhibitors and angiotensin receptor antagonists in patients after renal transplantation is safe. Favorable effects of both substances on albuminuria were detectable in patients who showed no signs of chronic allograft dysfunction according to the usual criteria. Therefore, a nephroprotective effect of candesartan as well as of perindopril, is highly probable in patients after renal transplantation. Further investigations regarding routine use in these patients are therefore mandatory.

Adult↗
PubMed2001

Quantitative heel ultrasound in assessment of bone structure in renal transplant recipients.

Many patients with advanced renal disease have osteopenia or even osteoporosis by the definition of the World Health Organization based on bone mineral density (BMD). Dual-energy X-ray absorptiometry (DXA), the standard method to assess BMD, is not always available. Quantitative heel ultrasound (QUS) is an inexpensive, mobile, and radiation-free diagnostic alternative, yet few data address this method's usefulness in patients with renal disease. The present study assessed the value of QUS in detecting changes in bone structure in renal transplant recipients compared with DXA. In a cross-sectional analysis, 50 patients (29 women) with a mean age of 50 +/- 13 years, mean time since transplantation of 60 months (range, 1 to 205 months), and stable renal allograft function were studied. BMD was quantified by DXA of the hip and spine. QUS of the left heel measured broadband ultrasound attenuation (BUA) and speed of sound (SOS). Stiffness index (SI) was calculated as SI = (0.67 * BUA + 0.28 * SOS) - 420. DXA measurements established the diagnoses of osteopenia and osteoporosis in 49% and 22% of the patients, respectively. Femoral neck BMD and QUS parameters showed good correlation (r = 0.638; P < 0.001). Sensitivities of BUA, SOS, and SI for diagnosing osteoporosis were 100%, and specificities were 73%, 76%, and 78%, respectively. Positive predictive values were 50%, 53%, and 56%, and negative predictive values were 100%. QUS can be recommended for screening patients who do not have osteoporosis. Those suspected of osteopenic bone structure should be examined by additional DXA measurement for quantification before initiation of therapy.

Absorptiometry, Photon↗
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

[Therapy options in systemic AL-amyloidosis with renal involvement].

BACKGROUND AND OBJECTIVE: Despite significant efficacy of melphalan and prednisone in the therapy of systemic AL(light chain amyloid)amyloidosis the prognosis of the disease is poor. In patients with severe renal manifestation the reported results of low-dose melphalan therapy are inconclusive with respect to relief of clinical symptoms and overall prognosis. PATIENTS AND METHODS: We report our results of therapy in a group of 22 patients (8 women, 14 men, mean age 60 years) with renal involvement as the main manifestation of systemic AL-amyloidosis without overt myeloma. RESULTS: Ten patients were treated with low doses of melphalan and prednisone. No significant clinical improvement was observed in any case: the patients died an average of 12 months after diagnosis of the disease. Three patients were treated with high doses of melphalan followed by autologous stem cell transplantation. One patient died due to septicaemia after high-dose chemotherapy. Two of the patients experienced significant remission and live virtually free of clinical symptoms 12 and 18 months after therapy. Nine patients were treated only symptomatically: four of them were alive an average of 30 months after diagnosis of systemic AL-amyloidosis. CONCLUSIONS: Only high-dose melphalan therapy offered a realistic chance of amelioration of clinical symptoms in our group of patients, although therapy-associated risks seem to be high. In patients with severe renal amyloidosis, who are not considered for high-dose therapy, particularly careful consideration of potential benefits and possible risks of conventional melphalan therapy is necessary, because the results of this approach are in doubt.

Adult↗
PubMed2000

AL-amyloidosis of the kidney initially presenting as minimal change glomerulonephritis.

Small amounts of amyloid in kidney biopsy specimens may be missed on routine examination unless specifically targeted. Occasionally, this oversight results in a diagnosis of minimal change glomerulonephritis (MCGN). This misdiagnosis may be facilitated by the fact that typical "minimal changes" with flattening and effacement of the epithelial foot processes can be found in capillary loops directly affected by amyloid deposition as well as in capillary loops of glomeruli with only mild amyloid deposition in the mesangium. Repeatedly, the diagnosis of MCGN had to be corrected to renal amyloidosis when re-examination by special techniques succeeded in detecting even small amounts of amyloid fibrils. We present the case of a previously healthy 49-year-old man who suddenly developed nephrotic syndrome. A first renal biopsy showed MCGN. Proteinuria remained refractory to immunosuppressive treatments, and creatinine clearance deteriorated rapidly. Two years later, a repeat renal biopsy showed AL-amyloidosis. In this case, re-examination of the first biopsy in the light of the final diagnosis again did not show any deposition of amyloid fibrils. We suspect that proteinuria and epithelial podocyte changes in amyloidosis are caused by factors other than deposition of amyloid fibrils itself. Possibly a cytokine release during the early fibril formation leads to abnormalities even before the typical structural changes of renal amyloidosis can be detected. This is analogous to the hypothesis of a circulating factor that leads to proteinuria in focal segmental glomerulosclerosis or the speculation of altered lymphokine expression associated with the development of MCGN in Hodgkin's disease.

Amyloidosis↗
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

[Systemic Al-amyloidosis. Clinical course and limits of melphalan therapy].

BACKGROUND: Despite significant effects of melphalan and prednisone in the therapy of systemic AL-amyloidosis, overall prognosis is poor and remission of clinical symptoms cannot generally be expected. The course of the disease and results of therapy are possibly influenced by the degree and distribution of organ manifestation at the time of diagnosis. We report a group of patients with renal involvement as the main manifestation of disease. PATIENTS: Fifteen patients with systemic Al-amyloidosis without symptomatic myeloma (4 women, 11 men, median age 61 [34 to 71] years) have been attended to at our department and were treated throughout the course of the disease. RESULTS: Since primary symptoms were frequently unspecific, the maximum time to diagnosis came to 28 months. Renal involvement was primarily evident at the time of diagnosis when all patients manifested proteinuria or renal insufficiency. Ten patients were treated with a melphalan and prednisone containing chemotherapeutic protocol. A significant clinical improvement was observed in no case. One patient in an advanced stage of disease died after the administration of a high-dose regimen of melphalan with blood stem-cell support subsequent to sepsis. CONCLUSION: We do not see an absolute indication for chemotherapy. The unfavorable prognosis--14 patients died an average of 13 months after diagnosis--requires a particularly careful consideration of potential benefits and possible risks accompanying cytostatic therapy.

Adult↗
PubMed1995

[Doppler sonographic evaluation of the effectiveness of an antirejection treatment after kidney transplantation].

Data on 64 rejection reactions in 108 consecutive patients after renal transplantation (61 males, 47 females; mean age 42.8 +/- 12.9 years) were analysed to test what Doppler sonographic measurements can be used to predict whether a given drug regimen is able to suppress rejection. Results were compared with renal function and histological evidence of rejection. The >> pulsatility index << (PI), which is dependent on flow resistance, was determined by Doppler echocardiography: it increases on rejection (measurements made 2.0 +/- 1.1 days apart). The rejection reaction was successfully controlled by drugs (methylprednisolone, azathioprine and cyclosporin) in 44 patients (group 1), but not in 20 patients (group 2). PI before rejection (group 1: 1.8 +/- 0.5; group 2: 1.7 +/- 0.6), PI during histologically confirmed rejection (2.6 +/- 1.2 and 3.1 +/- 1.4, respectively), the size of difference between these values, and parameters of renal function provided no pointers to any drug efficacy in suppressing rejection. But individual changes in PI during suppression treatment proved to be of outstanding value (P < 0.00005). Signs of florid rejection at the end of treatment period correlated with a rising PI in 13 of 17 rejection episodes, while PI fell in only 7 of 47 episodes. Vascular signs of rejection tended to be poor predictors of rejection (P .028). - These findings indicate that serial Doppler sonography can be helpful in monitoring antirejection treatment.

Adult↗