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Biomedical subjects

K L Schulte

Publications and source records attributed to K L Schulte.

At least 19 recordsLinked to original sources

[Hemobahn endoprosthesis: experience with percutaneous placing in the arteria femoralis superficialis].

The self-expanding Polytetrafluoroethylene-lined nitinolstent Hemobahn offers from its design a prophylaxis for re-occlusion after angioplasty of long femoral artery occlusions. During the last two years we placed in 33 patients at 35 extremities a total of 53 Hemobahns. Fontaine's clinical stages were: 30 x IIb, 1 x III and 4 x IV. The treated lesions were femoral stenoses (3x) and occlusions (32x with mean distance 12 cm). Follow-up-visits were after 3, 6 and 12 months. The mean ankle-brachial-index changed from 0.49 to 0.85, post-interventional Fontaine's stages were: 24 x I, 5 x IIa, 2 x IIb and 4 x IV. The primary inhospital patency rate was 91%. After 3 months all primary/secondary patency rates were: 77%/87%, after 6 months 62%/85% and after 1 year 40%/67%. Causes for re-occlusions were a poor "run off", calcifications and multiple vessel lesions. The results for "ideal indications" were much better. Such "ideal indications" applied to: > or = 1 cm "healthy" proximal and distal vascular segments, missing lesions in the popliteal artery, at least one open lower leg vessel and no severe calcifications. The primary/secondary patency rate was inhospital 100% (n = 23), after 3 months 95/100%, after 6 months 85/100% and after 1 year 80/100%. Side effects were local haematoma, pain in the prosthesis and temporarily temperature reactions. Sonographically no re-stenoses at the limb ends were observed. Hemobahn-endoprostheses are suited for therapy of long femoral artery occlusions. The medium patency rate of "ideal indications" is higher than that of angioplasty with or without uncovered stents.

Aged↗

Anticoagulation: the present and future.

Thrombin is a central bioregulator of coagulation and is therefore a key target in the therapeutic prevention and treatment of thromboembolic disorders, including deep vein thrombosis and pulmonary embolism. The current mainstays of anticoagulation treatment are heparins, which are indirect thrombin inhibitors, and coumarins, such as warfarin, which modulate the synthesis of vitamin K-dependent proteins. Although efficacious and widely used, heparins and coumarins have limitations because their pharmacokinetics and anticoagulant effects are unpredictable, with the risk of bleeding and other complications resulting in the need for close monitoring with their use. Low-molecular-weight heparins (LMWHs) provide a more predictable anticoagulant response, but their use is limited by the need for subcutaneous administration. In addition, discontinuation of heparin treatment can result in a thrombotic rebound due to the inability of these compounds to inhibit clot-bound thrombin. Direct thrombin inhibitors (DTI) are able to target both free and clot-bound thrombin. The first to be used was hirudin, but DTIs with lower molecular weights, such as DuP 714, PPACK, and efegatran, have subsequently been developed, and these agents are better able to inhibit clot-bound thrombin and the thrombotic processes that take place at sites of arterial damage. Such compounds inhibit thrombin by covalently binding to it, but this can result in toxicity and nonspecific binding. The development of reversible noncovalent DTIs, such as inogatran and melagatran, has resulted in safer, more specific and predictable anticoagulant treatment. Oral DTIs, such as ximelagatran, are set to provide a further breakthrough in the prophylaxis and treatment of thrombosis.

Administration, Oral↗

Underestimation of 24-hour hypotensive efficacy of nifedipine GITS versus enalapril: ambulatory recording as an adjunct to clinical blood pressure measurement.

AIMS: Short-acting calcium entry blockers should be used primarily in slow-release form. Furthermore, studies of the antihypertensive efficacy of drugs can be negatively influenced by between 15% and 30% of the enrolled patients not being hypertensive according to ambulatory blood pressure (BP) measurement. Thus, a randomized double-blind multicenter parallel-group study was conducted to compare the effect of nifedipine GITS (gastrointestinal therapeutic system) with enalapril. METHODS AND RESULTS: After a 2-week placebo run-in period, 186 patients with a sitting diastolic BP > or = 95 mmHg were enrolled for an 8-week treatment period. They received 30-60 mg nifedipine GITS or 5-10 mg enalapril. Diastolic BP fell comparably from 99 to 87 mmHg (p < 0.01) in the nifedipine GITS group, and from 100 to 88 mmHg (p < 0.01) in the enalapril group. The increase in BP 2 h before waking, however, was suppressed significantly more by nifedipine. Furthermore, this study highlighted the existence of "whitecoat" hypertension in a number of patients, especially when clinical BP was used to identify hypertension. Of the patients who had been identified as hypertensive before randomization by standardized BP measurement, 53 (28.5%) were identified as non-hypertensives by 24-h BP monitoring. This led to an underestimation of the efficacy of the antihypertensive therapy. CONCLUSION: Nifedipine GITS as well as enalapril are comparably effective antihypertensive drugs.

Adult↗

Captopril test: time over?

OBJECTIVE: The role of non-invasive tests for the detection of renovascular hypertension is still a matter of controversy. The 'captopril test' is widely used; its clinical usefulness, however, remains questionable. The aim of the current study was therefore to report our own experience and to review the published data on the diagnostic significance of the test. PATIENTS AND METHODS: Data from 485 hypertensive patients who underwent a captopril test in consecutive order at our institution were analysed retrospectively. After a 30-min resting period in the supine position 50 mg of captopril was given orally. Blood was collected before and 90 min after dosage for the determination of plasma renin concentration (normal range 3.5-8.0 ng/ml/h). An increase by 100% or more of the baseline value was considered a positive response. Blood pressure was recorded at baseline and at 90 min. RESULTS: A positive response was present in 62 patients; further diagnostic work-up revealed significant renal artery stenosis in 11 of these patients. In the 423 patients with a negative response renal artery stenosis was found in three cases. With some limitations of retrospective analyses in mind, sensitivity and specificity of the test were calculated as 79% and 89%, respectively. No severe complication occurred during the test. CONCLUSION: Our data on the diagnostic indices and the safety of the captopril test are in good agreement with most published series. Altogether, available data suggest that the captopril test has a limited diagnostic accuracy as a screening test for the detection of renovascular hypertension. New radiologic non-invasive techniques with greater diagnostic value are therefore likely to challenge the clinical role of the test in the future.

Adolescent↗

Clonidine suppression test revisited.

BACKGROUND: The diagnosis of pheochromocytoma may be difficult because the clinical picture is variable. OBJECTIVE: The purpose of this paper is to report our experience and to review the published data on the diagnostic significance and risks of the clonidine suppression test in the diagnosis of pheochromocytoma. PATIENTS AND METHODS: 114 patients were evaluated for pheochromocytoma using the clonidine suppression test. RESULTS: The diagnosis was established in four patients. Overall accuracy of the test in our own series was 98% when the normal response to clonidine was defined as total plasma catecholamines of less than 500 ng/L, or less than 70% of the baseline value. No serious complication was noted. CONCLUSION: Our data and the published series demonstrate that the clonidine suppression test is accurate and safe in patients with suspected pheochromocytoma.

Adrenal Gland Neoplasms↗

[Screening and diagnosis for eliminating renovascular hypertension. Value of 24-hour blood pressure monitoring and color-coded duplex ultrasound diagnosis].

BACKGROUND: Direct renal angiography is still the method of choice for identification of renal artery stenosis. Newer non-invasive diagnostic methods include color coded duplex sonography and also ambulatory 24-h blood pressure monitoring, since in a large proportion of patients with secondary forms of hypertension the usual blood pressure fall during nighttime disappears. PATIENTS AND METHODS: In a prospective in-hospital study we investigated 86 patients with suspected renovascular hypertension. Circadian blood pressure was measured oscillometrically and color coded duplex sonography was performed immediately before direct renal angiography. RESULTS: Angiography revealed renal artery stenosis (> or = 50%) in 42 patients. This compared to a sensitivity of 92.9% and specificity of 91.7% for the use of sonography in those patients (70.4%) who could be adequately examined. Mean 24-h pressure values as well as standard deviations of blood pressure means as an indicator for blood pressure variability were not different in the 2 groups of patients, when all the data were analysed together and also when the data for nighttime and daytime were examined separately. The percent of blood pressure fall during nighttime was also not different in the 2 groups. In both groups 4 hypertensive patients had a blood pressure increase during nighttime. In 11 patients without renal artery stenosis a blood pressure fall of < 10% was observed, compared to 12 patients with renal artery stenosis. The circadian pattern of pulse rate was similar in both groups. CONCLUSION: We conclude that ambulatory blood pressure monitoring has a considerably lower diagnostic value for renal artery stenosis compared to angiography and also to color duplex sonography. This method therefore does not appear to be an appropriate screening approach for this kind of secondary hypertension. The color coded duplex sonography, however, seems to be the best non-invasive diagnostic method in those patients, who can be adequately examined.

Adolescent↗

Color-coded duplex sonography for noninvasive diagnosis and grading of renal artery stenosis.

The accuracy of color-coded duplex sonography (CCDS) in screening hypertensive patients for renal artery stenosis (RAS) was assessed using a semi-quantitative waveform analysis. Our special aims were to separate between moderate and high grade stenoses and to evaluate the accuracy of the method in imaging both the whole course of the renal arteries and accessory renal arteries. Included in the prospective, angiographically controlled study were 135 consecutive patients with 268 renal arteries, of which 195 arteries (73%) could be visualized both proximally and distally by CCDS. Only three of 15 accessory renal arteries could be identified by CCDS. In 42 RAS > or = 50% sensitivity of CCDS was 93%, specificity 92%, and overall accuracy 92%. The sensitivity in identifying RAS > or = 75% was 92%, and none of the high grade stenoses were missed. Because of difficulties in visualizing the middle portion of the renal artery, we carefully examined this part of the artery in 116 additional patients. Whereas the proximal and the distal parts could be visualized in 77% of the renal arteries, signals from the middle third could be derived only in 60% on the right, and in 39% on the left side. Provided that the renal arteries were visualized both proximally and distally, a hemodynamically effective RAS could be excluded with high probability. Moreover, exact grading of high-grade stenoses was possible in all cases but one. An advantage of CCDS over conventional duplex sonography appears to be the time-saving examination. Since a low prevalence of RAS impairs the positive predictive value of CCDS, the examination should be reserved for patients with a strong clinical suspicion of renovascular hypertension.

Adolescent↗

24 h anti-anginal and anti-ischaemic effects with once daily felodipine. A double-blind comparison with nifedipine, twice daily, and placebo in patients with stable exercise induced angina pectoris.

The effects, as monotherapy, of felodipine ER 10 mg o.m. and nifedipine SR 20 mg b.d. were compared in a double-blind, randomized, placebo-controlled, three-way cross-over trial in 43 patients with stable exercise-induced angina pectoris. The exercise tests were performed at the end of dosage interval (i.e. 24 h after felodipine ER, 12 h after nifedipine SR) and at the expected peak time of 3 h post dose. Felodipine and nifedipine improved exercise duration by 66 and 50 s, respectively, (P < 0.001) compared with placebo at the end of the dosing interval. Time to the end of exercise showed no statistically significant difference between the two calcium antagonists. The onset of anginal pain and time to 1 mm ST depression were significantly more delayed by felodipine ER than nifedipine SR (22 s and 19 s, respectively, P < 0.05). Both felodipine and nifedipine decreased the pain score and rate pressure product at the highest comparable work load. Overall tolerability was good for both drugs.

Administration, Oral↗

E-selectin polymorphism and atherosclerosis: an association study.

Adhesion molecules like the members of the selectin family participate in the interaction between leukocytes and the endothelium. They are also involved in the pathogenesis of atherosclerotic processes. To contribute to the analysis of the genetic background of atherosclerosis we searched for DNA polymorphisms in the genes encoding adhesion molecules especially E-selectin which seems to be expressed only in activated endothelium. An adenine to cytosine substitution for cDNA position 561 resulting in an amino acid exchange from serine to arginine (position 128) was detected in the epidermal growth factor like domain. A significantly higher mutation frequency (P = 0.02) was observed in 97 patients aged 50 years or less with angiographically proven severe atherosclerosis (allele frequency of arginine 0.155) compared with an unselected population (allele frequency of arginine 0.088) as well as in 40 patients aged 40 years or less (allele frequency of arginine 0.21, P = 0.0025). These data suggest that the 128-serine/arginine polymorphism is associated with a higher risk for early severe atherosclerosis.

Adult↗

Quinapril, hydrochlorothiazide, and combination in patients with moderate to severe hypertension.

This 8-week, double-blind, multicentre study compared the efficacy and safety of the combination of quinapril and hydrochlorothiazide (HCTZ) with each drug as monotherapy. Outpatients with moderate to severe hypertension defined as supine diastolic blood pressure (DBP) > or = 105 mmHg and < or = 120 mmHg at the end of a 2 to 4-week placebo-baseline period were randomly assigned to one of the three treatments: once-daily 10 mg quinapril plus 12.5 mg HCTZ or monotherapy with these doses. After 4 weeks, the doses were to be doubled for the remaining 4 weeks. Three hundred and sixty-eight patients were randomized to double-blind medication; 346 completed the study. Seven patients withdrew due to lack of efficacy. Four patients withdrew due to side effects. In all three treatment groups, clinically significant reductions in DBP were achieved. Combination therapy was statistically more effective than each component taken as monotherapy. Adverse events were infrequent in all treatment groups. No patients experienced symptomatic hypotension or orthostatic hypotension.

Angiotensin-Converting Enzyme Inhibitors↗

Relationships between ambulatory blood pressure, forearm vascular resistance, and left ventricular mass in hypertensive and normotensive subjects.

Ambulant 24 h blood pressure was recorded in 97 untreated hypertensive subjects (50 with, 47 without echocardiographic signs of left ventricular hypertrophy) and 45 matched normotensive subjects. Forearm vascular resistance was calculated from mean blood pressure and blood flow, which was measured by venous plethysmography during reactive hyperemia. Blood pressure variability was calculated by standard deviations of pressure values. Systolic 24 h blood pressure exhibited the closest correlation with left ventricular mass index in hypertensives (4 = 0.48; P < .001). No relation could be found between blood pressure fall during the night and left ventricular mass index. Furthermore, body weight was a significant correlate of left ventricular mass (r = 0.53; P < .001). Regression analysis indicated that body weight and 24 h blood pressure were the principal determinants of left ventricular mass. Blood pressure variability was significantly higher in hypertensive than in normotensive subjects (P < .05). The highest vascular resistance was found in hypertensive patients with left ventricular hypertrophy compared with the other groups (P < .05). A significant close correlation between systolic resting as well as 24 h blood pressure and vascular resistance was identified for the group of hypertensives and all subjects investigated. Furthermore, left ventricular mass index and vascular resistance were correlated (in hypertensives: r = 0.32; P < .01). The extent of left ventricular mass index and forearm vascular resistance are proportional to the severity of hypertension. As vascular resistance and left ventricular mass are also related, these findings could speak for a parallel development of total peripheral resistance and left ventricular hypertrophy in essential hypertension.

Adult↗

Clinical pharmacokinetics of angiotensin converting enzyme (ACE) inhibitors in renal failure.

Arterial hypertension occurs frequently in patients with chronic renal failure. Antihypertensive treatment of arterial hypertension with angiotensin converting enzyme (ACE) inhibitors has been shown to be effective with a low incidence of adverse effects compared with other drug classes. Furthermore, treatment with ACE inhibitors may slow the progression of renal function impairment in certain groups of patients, such as those with diabetes. Most ACE inhibitors are prodrugs which are converted by hepatic esterolysis to an active diacid metabolite. Only captopril and lisinopril have sufficient oral bioavailability and are given as active drugs. ACE inhibitors can be subdivided into 3 classes with regard to the active group: the majority of ACE inhibitors are carboxyl-containing drugs, a new class of ACE inhibitors possess a phosphoryl-group and captopril and related compounds are sulfhydryl-containing drugs. The predominant elimination pathway of ACE inhibitors is excretion via the kidneys. Therefore, renal insufficiency is associated with reduced elimination of most ACE inhibitors and, thus, altered pharmacokinetic properties. This is most evident in chronic renal failure when glomerular filtration rates (GFR) are < 30 to 40 ml/min (1.8 to 2.4 L/h). As renal clearance decreases, the peak plasma concentration and area under the plasma concentration-time curve of the active drugs or diacids are increased and time to peak concentrations and half-life are prolonged. However, there are large between-drug differences in the changes in pharmacokinetic parameters, resulting in different degrees of drug accumulation after consecutive administration. This leads, for example, to high accumulation rates for drugs such as lisinopril, or cilazaprilat. In contrast, fosinopril, which is also excreted to a large extent by the hepatobiliary pathway, does not seem to accumulate in renal failure. In general, pharmacokinetics and conversion of prodrugs seem to be slightly affected in chronic renal failure; however, these changes do not appear to be clinically relevant. Efficiency of clearance for prodrugs or active drugs and their respective metabolites by haemodialysis or peritoneal dialysis varies considerably. For some ACE inhibitors, such as captopril or enalapril, the high elimination fraction by haemodialysis necessitates a supplemental dose after dialysis. Other ACE inhibitors, such as quinapril or cilazapril, are only poorly eliminated by haemodialysis or peritoneal dialysis. Dosage recommendations for treatment with ACE inhibitors in chronic renal failure depend on the specific pharmacokinetic properties of the various agents. For most ACE inhibitors, dosage adjustment is recommended in moderate and severe impairment of renal function, with resultant dosages being 25 to 50% of those recommended for patients with normal renal function.

Angiotensin-Converting Enzyme Inhibitors↗

Relation of regression of left ventricular hypertrophy to changes in ambulatory blood pressure after long-term therapy with perindopril versus nifedipine.

Casual as well as ambulatory 24-hour blood pressure (BP) and echocardiographic parameters were studied in 40 patients with untreated or insufficiently treated mild to moderate essential hypertension. Left ventricular (LV) hypertrophy was assessed before and after 24 weeks of therapy with either the converting enzyme inhibitor perindopril or the calcium antagonist nifedipine. The design was a double-blind parallel study with a placebo run-in period. Patients received a daily oral dosage of either 4 to 8 mg of perindopril or 40 to 80 mg of nifedipine in slow-release form. A diuretic (25 mg/day of hydrochlorothiazide) was added in nonresponders (greater than 90 mm Hg casual diastolic BP). Once-daily perindopril and twice-daily nifedipine comparably reduced both casual and ambulatory BP throughout 24 hours (p less than 0.01) without affecting 24-hour heart rate. Six subjects withdrew from the nifedipine group and 4 from the perindopril group. After 12 and 24 weeks of therapy, LV hypertrophy was significantly reduced by both agents. Before active treatment was begun, LV mass index was more closely correlated to 24-hour (p less than 0.001) than to casual BP. This correlation disappeared after treatment with both agents. The correlation between ambulatory systolic day-time BP and LV mass was only still present (r = 0.54; p less than 0.05) after 24 weeks of treatment with nifedipine. It is concluded that regression of LV hypertrophy during converting enzyme inhibition or calcium antagonism may be partly independent of dosage and magnitude of 24-hour BP decrease.

Adult↗