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Biomedical subjects

B Kutkuhn

Publications and source records attributed to B Kutkuhn.

At least 19 recordsLinked to original sources

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↗

[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↗

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↗

[Mycophenolatemofetil in ocular immunological disorders. A survey of the literature with 3 case reports].

BACKGROUND: Up to now ophthalmologists have only a small number of substances in their therapeutic armamentarium for the treatment of ocular immunological disorders. These are very potent agents, and any rapidly proliferating cells are extremely sensitive to such agents, thus the possibility of severe side effects is great. Mycophenolatemofetil (MMF) has been shown to be effective in preventing acute graft rejection following clinical renal and cardiac transplantation with a low risk of adverse events. Likewise MMF was effective in the treatment of experimental immunological disorders. A review of literature was performed in Medline. CASE REPORTS: We report on the effective use of MMF in a patient with ocular cicatricial pemphigoid, the switch from Cyclosporin A (CSA) therapy to MMF therapy following high-risk keratoplasty due to CSA allergy and about the combination therapy (CSA/MMF) in a patient following high risk keratoplasty, in whom CSA monotherapy was not sufficient to prevent allograft rejection. CONCLUSIONS: In these three cases MMF has been shown to be a safe and effective agent for the treatment of ocular immunological disorders. Whether these beneficial casuistic experiences will hold true will be depended on the outcome of longterm studies underway.

Corneal Transplantation↗

Haemolytic-uraemic syndrome and thrombotic-thrombocytopenic purpura in adults: clinical findings and prognostic factors for death and end-stage renal disease.

BACKGROUND: Left untreated, haemolytic-uraemic syndrome (HUS) and thrombotic-thrombocytopenic purpura (TTP) in adults have a poor prognosis with mortality rates reaching 90%. Patients who survive often develop end-stage renal disease. Because of similarities in clinical and morphological findings, both diseases are considered as one entity referred to as HUS-TTP syndrome. METHODS: From 1974 to January 1995, 45 adult patients received treatment for HUS-TTP at our clinic. By stepwise logistic regression analyses, we examined how known risk factors and plasma exchange with fresh-frozen plasma (PE) influenced mortality and end-stage renal disease. RESULTS: Three of 45 patients died (7%). Though we were not able to find significant predictors of mortality, low haemoglobin levels (5.93 +/- 0.32 vs 9.10 +/- 2.16 g/dl) and high leukocyte counts on admission (15.830 +/- 3.690 vs 11.150 +/- 4.580 microliters-1) appeared to indicate an unfavourable outcome. Regarding the development of end-stage renal disease, PE proved to be the only favourable indicator (P = 0.0001). PE was performed in 30 patients 3-20 times (9.2 +/- 4.8, mean +/- SD). Of 28 surviving patients treated with PE, only four developed end-stage renal disease, whereas dialysis was necessary in 11 of 14 patients not treated with PE. Application of PE led to an 81.8% reduction of the relative risk of developing end-stage renal disease. An additional prognostic influence of other potential risk factors such as age, sex, platelet count on admission, lactate dehydrogenase serum levels, serum creatinine, blood pressure, prodromal disease, and renal histology was not found. CONCLUSION: This retrospective clinical study confirms the therapeutic value of plasma exchange with fresh-frozen plasma to maintain renal function in patients with HUS-TTP.

Adolescent↗

[Hypertension and insulin resistance].

Non insulin dependent diabetes mellitus (NIDDM) and obesity are defined as classical insulin resistant states. Essential hypertension is now also considered to be an insulin resistant state, even in absence of NIDDM or obesity, as shown in epidemiological, clinical and experimental studies. Neither the underlying mechanism nor a direct causality between the two phenomena has been detected as yet, but different hypotheses have been postulated where, on the one hand, insulin resistance and hypertension are considered to be causally related and, on the other hand, they are considered to be parallel phenomena due to genetic and acquired factors. The clarification of the connection between hypertension and insulin resistance seems to be of great clinical importance, since they are both independent risk factors for cardiovascular disease and mortality from cardiovascular complications. This paper gives an overview of the results of recent research on the possible underlying pathogenetic mechanisms linking hypertension and insulin resistance.

Animals↗

Apolipoprotein A, fibrinogen, age, and history of stroke are predictors of death in dialysed diabetic patients: a prospective study in 412 subjects.

BACKGROUND: Diabetic patients with end-stage renal failure (ESRD) have a high cardiovascular morbidity and mortality. The underlying mechanisms are not completely elucidated. The aim of our study was to define predictors of death in diabetic patients with end-stage renal disease. PATIENTS AND METHODS: We performed a prospective study in 35 dialysis centres in Germany between 1985 and 1994. To evaluate predictors and risk factors in this population we examined 412 diabetic patients at the time of admission to dialysis treatment (peritoneal dialysis (PD) or haemodialysis (HD)). Classification of the type of diabetes was done according the criteria of the National Diabetes Data Group [1,2]. Items assessed at the time of admission were coronary artery disease (CAD), peripheral occlusive disease (POD), and stroke. CAD was defined as a history of myocardial infarction with the corresponding changes in the ECG or luminal narrowing by more than 50% in at least one coronary artery upon coronarangiography; POD was defined as claudication and/or brachial-tibial ratio (BTR) less than 0.9 or a history of amputation. Assessment of the nutritional state comprised body mass index, skinfold thickness of the upper arm and lateral thorax area, and urea concentration. Cholesterol, HDL, LDL, apolipoprotein A (ApoA-I) and B (ApoB), triglycerides, lipoprotein(a) (Lp(a)), and fibrinogen were measured. As an index of disturbed cardiac innervation beat-to-beat variation was measured. Outcome measurements were causes of death (i.e. cardiac and non-cardiac) and time of survival. RESULTS: One hundred and eighty of 412 (44%) patients died during the observation period. Patients who died were older (61 +/- 12 versus 53 +/- 15 years P < 0.0001), had lower skin fold thickness (13.1 +/- 6.0 versus 15.1 +/- 7.3 mm P < 0.04), lower ApoA-I (100 +/- 35 versus 111 +/- 32 mg/dl P < 0.005) and higher fibrinogen (515 +/- 146 versus 451 +/- 155 mg/dl P < 0.02). Type II diabetic patients had a lower mean survival time than type I (34 versus 66 months P < 0.0006). The mode of renal replacement therapy (PD or HD) had no adverse effect on survival time. Survivors less frequently had a history of CAD, POD and stroke than non-survivors. In multivariate analysis ApoA-I, fibrinogen, age and stroke were independent predictors of cardiac and non-cardiac death in diabetic patients with end-stage renal failure. Lipid values and nutritional state did not independently predict the overall and cardiovascular mortality. CONCLUSION: This study in dialysed diabetic patients identifies several predictors of death, some of which are susceptible to intervention.

Adult↗

Apolipoprotein B, fibrinogen, HDL cholesterol, and apolipoprotein(a) phenotypes predict coronary artery disease in hemodialysis patients.

Patients with end-stage renal disease have a markedly elevated risk for coronary artery disease (CAD). Lipids and most lipoproteins, however, seem to be not predictive for CAD in these patients. Although there is clear evidence that lipoprotein(a) [Lp(a)] is significantly elevated in these patients, no study with a sufficiently large group of hemodialysis patients has investigated the relationship between CAD and Lp(a), as well as the genetically determined apolipoprotein(a) [apo(a)] phenotype. This cross-sectional study determines the prevalence of CAD in relation to the cardiovascular risk profile in an unselected population of 607 hemodialysis patients, of which 33% were diabetic patients. Twenty-six percent (n = 158) of all patients suffered from CAD as diagnosed by a definitive myocardial infarction (n = 102) and/or at least one stenosis >50% of a coronary artery (n = 143). In univariate analysis, several classic risk factors, including the concentration of lipids, lipoproteins, apolipoproteins, and fibrinogen, correlated with CAD. Lp(a) in patients with CAD showed only a tendency to higher levels, without reaching significance, compared with patients without CAD (26.6 +/- 30.8 mg/dl versus 22.1 +/- 30.4 mg/dl, P = 0.10). The frequency of low molecular weight apo(a) isoforms, however, was significantly greater in the group with CAD (34.8% versus 23.6%, P < 0.01). Stepwise logistic regression analysis found seven variables associated with CAD: apolipoprotein B, the low molecular weight apo(a) phenotype, male sex, age, fibrinogen, diabetes mellitus, and HDL cholesterol. The association of these variables with CAD differed depending on age. These results indicate that, besides classic risk factors such as age, sex, and diabetes mellitus, additional factors of the lipoprotein and fibrinolytic system contribute to the high prevalence of CAD in hemodialysis patients.

Adult↗

Development of insulin resistance and elevated blood pressure during therapy with cyclosporine A.

OBJECTIVES: Essential hypertension and insulin resistance frequently coexist; cyclosporine A (CsA) is known to induce hypertension which has been used as a model for essential hypertension. The present study aimed to evaluate whether elevated blood pressure and insulin resistance coexist during CsA therapy to prove the similarity between essential hypertension and CsA induced hypertension. DESIGN: Normotensive patients who underwent keratoplasty were investigated before and during single therapy with CsA (2-4 mg/kg body weight) in an open A-B Trial. PATIENTS: Eighteen lean, normotensive patients without metabolic disorders with normal renal function and without family history of hypertension or metabolic abnormalities. MAIN METHODS: Insulin sensitivity index was determined by the modified frequent sampling intravenous glucose tolerance test (FSIGT) and blood pressure was determined by indirect ambulatory blood pressure monitoring. RESULTS: Mean insulin sensitivity index (S1) was significantly reduced (p < 0.03) during treatment with CsA (4.4 +/- 2.6 x 10(-4) vs 2.8 +/- 2.0 x 10(-4)/min per microU/ml), whereas mean systolic daytime blood pressure increased from 126.4 +/- 10.8 mmHg to 135.7 +/- 11.8 mmHg (p < 0.02), as well as the corresponding diastolic blood pressure from 76.8 +/- 8.7 mmHg to 82.8 +/- 9.3 mmHg (p < 0.05). CONCLUSIONS: CsA therapy induces elevated blood pressure and insulin resistance as seen in patients with essential hypertension, thus CsA induced hypertension is considered to have pathophysiological similarities to essential hypertension.

Adult↗

Acute blockage of the renin system and differential renal vein renin determinations in the diagnosis of renovascular hypertension.

For validation of differential renal vein renin determinations in the diagnosis of renovascular hypertension (RVH), we investigated 102 patients suspected of suffering from RVH before and 1 h after administration of 25 mg captopril. Sensitivity, specificity and posterior probability for renin ratio (RR) and renin secretion (RS) were calculated based on 44 patients with proven RVH and 58 patients with primary hypertension (PH) using discriminant analysis. There is good (> 95%) and identical specificity of both variables under all conditions, whereas sensitivity remains poor even after Captopril administration (RR 23% vs. 32%; RS 20% vs. 34%). The posterior probabilities obtained by discriminant analysis revealed a cut-off point of 2.5 for the renin ratio and of 1.9 for the renin secretion. No change is observed after ACE inhibition. We conclude that the acute blockade of the renin system by captopril in differential renin sampling yields no advantages in diagnosing RVH and that there is no difference between RR and RS in the diagnosis of RVH.

Adult↗

[Repeated ingestion with suicidal intent of potentially lethal amounts of thallium].

30 minutes after drinking half a cup of rat poison a 16-year-old girl was admitted to hospital. In addition to various enteric detoxification measures forced dialysis was instituted and, after the urinary thallium level had become known (9 mg/l), haemodialysis was begun and ferric ferrocyanide (Prussian blue) administered (0.5 mg daily for six days). She had no symptoms at any time. After 10 days she was discharged. Five days after discharge she was again admitted, with colic-like abdominal pain, vomiting, paraesthesias of the hands and feet, and in a state of agitation. She had once again ingested rat poison, about one cup. Physical examination revealed little of consequence, except diffuse alopecia. Urinary thallium concentration was 37 mg/l. In the electrocardiogram the P-R interval was shortened to 0.11 s and T waves inverted in leads III and V1. Electronmicroscopy of cardiac and skeletal biopsies revealed lipid droplets, increased sarcoplasm and widening of some of the tubules. Treatment consisted of haemodialysis, forced diuresis (1 l urine/h), administration of ferric ferrocyanide, orthograde intestinal infusions and potassium substitution (serum level: 5 mmol/l). After 28 days the patient was discharged into psychiatric care.

Adolescent↗

Renin secretion and captopril stimulation in hypertensive renal transplant recipients.

Basal renin secretion and the diagnostic value of a captopril stimulation (captopril test) in identifying renovascular hypertension secondary to transplant renal artery stenosis was assessed in 69 patients with hypertension after renal transplantation. An increase of plasma renin activity of 260% 1 h after captopril was considered as a positive result, assuming renovascular hypertension. Six of 69 patients had a positive captopril test, of these patients 5 had transplant renal artery stenosis. These patients were treated with percutaneous transluminal angioplasty (PTA) or surgery. Based on angiographic results and blood pressure response after PTA or surgery the captopril test showed a sensitivity of 100% and a specificity of 92% in the identification of hemodynamically significant stenosis of the transplant artery. Therefore, the captopril test provides a suitable screening instrument for the differential diagnosis of hypertension following renal transplantation.

Adult↗

Colour Doppler ultrasound in the diagnosis of transplant renal artery stenosis.

The validity of colour Doppler ultrasound (CDU) in the detection of transplant renal artery stenosis (TRAS) was investigated. 93 patients presenting with deteriorating hypertension underwent CDU. Seven out of 93 patients (8%) were excluded from the study because of incomplete visualization of the transplant vessels. The CDU diagnosis of TRAS was made when all of the following criteria were present: 1. local increase in flow velocity exceeding 150% of the values found in other sections of the transplant artery and 2. marked turbulences in the artery distally of a region with local flow increase. 86 CDU examinations obtained in 86 patients [52 male, 34 female; mean age 45.7 +/- 12.6 years; examined on average 28.8 months (1-156) after transplantation] were compared with 40 angiographies. Patients showing stenosis in the CDU (n = 12) or receiving combined antihypertensive therapy with 3 or more drugs (n = 28) had an angiography performed. Angiography confirmed 11 out of the 12 arterial stenoses that had been found with CDU and detected one segment artery stenosis of 30-50% that was not detected by CDU. In 4 stenosed arteries, peak velocities were higher than the maximum velocity measurable with the pw-Doppler (higher than 350 cm/s). Peak velocities measured by CDU within 8 stenoses exceeded the flow speeds obtained elsewhere in the artery by 193 +/- 35% (286 +/- 82 cm/s). Using the criteria of stenosis as defined in this paper, CDU may be employed as screening method to detect TRAS with a sensitivity of 92% and a specificity of 96%.

Adult↗

[Prevention of acute renal failure in suprarenal aortic surgery. Results of a pilot study].

Acute renal failure continues to be a frequent complication after vascular operations with interruption of renal circulation. Aim of the study was to evaluate two methods to prevent postischemic renal failure after suprarenal aortic surgery: the pretreatment with Prostaglandin E1 and the organ perfusion with cold saline solution. 24 patients, who did not receive Prostaglandin E1 or cold organ perfusion were used as control (Group A). 37.5% of these patients (n = 9/24) developed acute renal failure. 3 needed hemodialysis postoperatively. Only 3 out of 26 patients (11.5%), who received PGE1 (Group B), showed deterioration of renal function with plasma creatinine values greater than 2 mg % and no patient needed dialysis. 6 out of 26 patients (23%), who received organ perfusion with cold saline (Group C), developed acute renal failure and in one case temporary hemodialysis was necessary. Plasma creatinine increased in the group A from 1.1 (0.1) mg % to 1.95 (0.4) mg % on third postoperative day and to 2.1 (0.4) mg % on discharge, while after pretreatment with PGE1 (Group B) plasma creatinine increased from 1.25 (0.1) mg % to 1.44 (0.1) mg %. In the group C creatinine increased from 1.3 (0.1) mg % to 1.77 (0.1) mg %. On discharge from the hospital plasma creatinine decreased to mean values of 1.25 (0.1) mg % in the group B and 1.5 (0.1) mg % in the group C. Intraoperative organ perfusion with cold saline and Prostaglandin E1 allows today complicated arterial reconstructions of both aorta and renal arteries with minimal risk of postischemic renal damage.

Acute Kidney Injury↗

[Renal stent implantation. The current indications, 2-year results and the possibilities for percutaneous stent recovery].

Use of the Strecker flexible balloon-expandable tantalum stent for treatment of renal artery stenosis after failed angioplasty or transaortic thrombendarterectomy was evaluated in 18 patients (17 hypertensive, 1 normotensive). Right (n = 10) and left (n = 6) renal arteries were involved; in 2 patients renal artery stenosis had developed after kidney transplantation. Indications for stent placement were inadequate immediate postangioplasty response (n = 16), and obstructing intimal flaps following transaortic endarterectomy (n = 2). Stent placement was technically successful (less than 20% residual stenosis) and patency was preserved in 14 patients. Mid-term results (mean, 12-13 months) of 11 patients showed restenoses (greater than 50%) in 2 patients, and improvement of hypertension in 8 patients. The Strecker stent may be helpful in treating residual stenosis after failed revascularization procedures of the renal arteries, although long-term efficacy of stent placement will not be known until trials with more subjects and longer follow-up periods are completed.

Adult↗

[Spontaneous renal artery dissection].

The clinical clues of sudden arterial hypertension, acute pain in the side, proteinuria, hematuria, abdominal bruits and renal failure are suspicious for spontaneous dissection of the renal arteries, even in the absence of one or more of the above-mentioned symptoms. To confirm the diagnosis and to provide appropriate therapy, immediate renal arteriography is mandatory, otherwise acute loss of renal tissue may occur. We report on one patient with spontaneous dissection of the renal arteries.

Aortic Dissection↗

[The value of noninvasive 24-hour blood pressure measurement in patients with renoparenchymal, renovascular or severe essential hypertension].

210 patients receiving antihypertensive treatment underwent non-invasive ambulatory blood-pressure monitoring for the first time. 44 suffered from chronic renal failure, 51 had been renal transplanted, 36 had chronic glomerulonephritis, 36 had renovascular hypertension, and 43 had essential hypertension with severe end-organ damage. We analyzed the Circadian rhythm and the rate of insufficient antihypertensive treatment. While mean daytime systolic and diastolic blood pressure were not different between groups, patients with chronic renal failure, renal transplant or glomerulonephritis showed a very high rate (95-72%) of absent nighttime blood-pressure reduction. In patients with renovascular hypertension or complicated essential hypertension there was a lower rate (69-40%) of absent nighttime blood pressure reduction. The ambulatory blood-pressure monitoring led to a modification of antihypertensive treatment in 78% of patients because of nighttime hypertension. We think that ambulatory blood-pressure monitoring is an essential tool for physicians treating patients with renal disease or complicated essential hypertension.

Antihypertensive Agents↗