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Biomedical subjects

R Hofmann

Publications and source records attributed to R Hofmann.

At least 91 records · Page 5Linked to original sources

Magnetic resonance imaging in the diagnosis of acute injured distal tibiofibular syndesmosis.

RATIONALE AND OBJECTIVES: This study assessed the diagnostic potential of magnetic resonance imaging for the evaluation of the tibiofibular syndesmosis. METHODS: A total of 38 patients with an acute ankle trauma and clinical suspicion of a syndesmotic tear were prospectively studied with conventional plain film radiography and magnetic resonance imaging. Magnetic resonance imaging studies included plain T1-weighted (T1-w) and T2-weighted (T2-w) sequences and contrast-enhanced T1-w sequences 0 to 3 days after trauma. All images were read by two independent radiologists before surgical intervention. Sensitivity and specificity were determined for the two observers and the concordance of the two observers were calculated using the interobserver analysis (Kappa-Test). Intraoperative inspection (n = 21) revealed rupture of the anterior tibiofibular ligament (ATIF) in 15 patients, intact ATIF in 6 patients, and intact posterior tibiofibular ligament (PTIF) in 21 cases. Clinical and follow-up examinations revealed an intact syndesmotic complex in another 17 patients. RESULTS: Primary diagnostic criteria for diagnosing a ligamentous tear included tibiofibular diastasis in conventional plain films; nonvisualization of the ATIF; an abnormal course, a wavy, irregular contour of the ligament; increased signal intensity of the ligament in T2-w sequences, in plain T1-w sequence, and marked enhancement in T1-w after contrast. Important secondary signs were defined as joint fluid in the tibiofibular space and prolapse of interspace fat. Highest diagnostic accuracy was achieved if three or more diagnostic criteria could be visualized. Both readers performed best with the enhanced T1-weighted and the T2-weighted images in transverse orientation. The interobserver analysis resulted in high concordance: Kappa = 0.9 (confidence interval: 0.76 to 1.00) for all patients, and in Kappa = 0.76 (confidence interval: 0.45 to 1.0) for surgically treated patients. CONCLUSIONS: Magnetic resonance imaging of the syndesmotic complex is a highly sensitive and specific tool for the pretherapeutic-evaluation of syndesmotic injury.

Acute Disease↗

Relative bioavailability of 3 different chlormezanone 200 mg preparations after single dose oral administration.

Eighteen male volunteers have been treated with 3 different oral formulations of chlormezanone according to a randomized 3-way change-over design. The test preparation was a tablet (Krewel), reference preparation 1 was a suspension (Krewel), and reference preparation 2 was a tablet (Muskel Trancopal, Sanofi Winthrop GmbH). All preparations contained 200 mg of chlormezanone. Divided in 3 periods the volunteers received single doses of the test and the 2 reference formulations, respectively. Blood samples have been drawn immediately prior to each administration and at 21 sampling points within 144 h after dosing. A wash-out period of 2 weeks was maintained between successive drug doses. Plasma concentrations of chlormezanone were determined by a validated reversed-phase HPLC method with UV detection, with a lower limit of quantification of 0.1 microgram/ml. The following mean values have been obtained for the test preparation: AUC0-infinity 121 micrograms x h/ml, Cmax of 2.9 micrograms/ml at 1.5 h, t1/2 38 h, after administration of the suspension: AUC0-infinity 111 micrograms x h/ml, Cmax 2.6 micrograms/ml, tmax 1.5 h, t1/2 40 h, and after administration of the reference tablet: AUC0-infinity 121 micrograms x h/ml, Cmax 3.0 micrograms/ml, tmax 1.6 h, t1/2 38 h. The test preparation shows a relative bioavailability of 109% compared to the suspension and has been proven to be bioequivalent to the reference tablet with regard to extent and rate of absorption.

Administration, Oral↗

Treatment of left ventricular hypertrophy in hypertensive patients with a combination of verapamil and captopril--a multicenter study.

UNLABELLED: The regression of left ventricular hypertrophy in hypertensive patients was evaluated in a multicenter study with a combination therapy of verapamil 120 mg and captopril 25 mg given once or twice daily. The degree of left ventricular hypertrophy was assessed using echocardiography, while hypertension was evaluated by means of twice daily blood pressure self-measurements and ambulatory blood pressure monitoring. RESULTS: An overall of 61 patients was evaluated. Left ventricular mass had decreased by 13.5% during the 6-month treatment period. This reduction neither correlated with the baseline left ventricular mass nor with the extent of blood pressure decrease. CONCLUSION: The combination therapy-verapamil 120 mg plus captopril 25 mg--is well tolerated by hypertensive patients with left ventricular hypertrophy and produced a decrease of left ventricular mass that is independent of the extent of blood pressure decrease.

Adult↗

[Changes in blood rheology and microcirculation after preparatory combined thrombocytapheresis and plasmapheresis].

INTRODUCTION: Because of anticoagulation, changes in blood composition, and--perhaps--extracorporeal circulation, donor apheresis should cause alterations in hemorheology and hence in the perfusion of the microvasculature. MATERIAL AND METHODS: 19 regular blood donors were included. According to our standard protocol for automated collection of blood components with the MCS 3p cell separator, we harvested 1 unit of platelets and 2 units of plasma in each case. Prior to, 1 h after, and 24 h after donation, the following parameters were measured: total serum protein (tsp), hematocrit (hc), whole blood and plasma viscosity (wbv/pv), red cell aggregability (rca) and blood flow velocity of the nail-fold capillaries (bfv). RESULTS: The following parameters decreased 1 h/24 h after donation: tsp (p < 0.001/p = 0.008), elastic wbv (p = 0.018/p < 0.001), viscous wbv (p = 0.85/p = 0.0031), pv (p < 0.001/p < 0.001), static rca (p < 0.001/p = 0.0073), dynamic rca (p < 0.001/p = 0.017). The hc showed an initial increase (p < 0.001) with a subsequent overshooting decrease after 24 h (p < 0.001). 1 h after donation bfv raised (p = 0.0065). It decreased after 24 h and remained only slightly higher than the initial level (p = 0.27). CONCLUSIONS: Automated combined collection of platelets and plasma gives rise to: i) Improvement of rheological properties of the donor's blood and increased bfv of his nail-fold capillaries within the 1st h after apheresis. ii) 24 h after donation the improved hemorheological properties remain demonstrable, but the bfv of nail-fold capillaries declines and shows a trend toward the starting-point. iii) Taken together, this is possibly reflecting adapted hemodynamic and vasoconstrictor regulation for altered hemorheological conditions.

Adaptation, Physiological↗

Clinical relevance of urokinase plasminogen activator, its receptor, and its inhibitor in patients with renal cell carcinoma.

BACKGROUND: Urokinase plasminogen activator (u-PA) plays a key role in the metastatic process by promoting plasmin mediated tissue degradation. Metastatic cell invasion requires localized proteolysis, which may be directed by u-PA receptor. The binding of u-PA and PAI-1 to the u-PA-receptor may cause internalization of the trimeric complex into the cell and activate a tyrosine-kinase. In a prospective study the u-PA, u-PA-R, and PAI-1 content in patients with renal cell carcinoma (RCC) and benign renal tissue were correlated with traditional prognostic factors such as the TNM staging, histologic grading, ploidy, and the clinical outcome of the patients. METHODS: One hundred fifty-two patients who underwent transperitoneal tumor nephrectomy for RCC were followed up for a mean of 23.9 months. u-PA, u-PA-R, and PAI-1 from the tumor tissue and corresponding benign renal tissue were quantified from detergent extracted tissue samples (1% Trinton-X-100 in triethanolamine-buffered saline) and measured with an enzyme-linked immunoadsorbent assay. RESULTS: PAI-1 significantly correlated with the prevalence of distant metastasis (M0: 10.04 vs. M1 23.79, P=0.02) and the development of new metastasis postoperatively (M0: 10.85 vs. M1 27.36, P=0.001). A cut-off level of 12 ng/mg protein for PAI-1 selected a group of patients at high risk for relapse. Forty-one patients had PAI-1 > 12 ng/mg with 6 relapses compared with 55 patients with PAI-1 < 12 ng/mg with 1 relapse during the follow-up. Content of mu-PA correlated with the development of distant metastases (log rank 4.32, P=0.037). A cut-off value of 0.84 ng/mg selected 2 groups: a group at high risk for metastasizing (u-PA > 0.84, n=11 with 9 events and a group at low risk (u-PA < 0.84 with 94 patients and 5 events). Applying a cut-off value of 0.85 for u-PA-R 2 groups could be discriminated: 31 patients had no relapse with u-PA-R < 0.85 and 18 had 3 recurrences with u-PA-R > 0.85 g/ml. CONCLUSIONS: u-PA, u-PA-R, and PAI-1 are strong and independent prognostic factors for predicting early relapse for RCC. Especially with PAI-1, a high and low risk group for disease free survival can be discriminated.

Biomarkers, Tumor↗

Autologous tissue cardiac valve for aortic valve replacement: technical aspects and early results.

BACKGROUND: The known complications of heterograft bioprostheses and homograft valves have renewed the interest in the use of autologous material. A new technique to construct a tissue prosthesis for aortic valve replacement using the patient's pericardium harvested at the time of operation was developed. The glutaraldehyde-tanned pericardium is mounted on a stent requiring no suturing. Intraoperative testing assures adequate valve function. METHODS: The autologous tissue cardiac valve was implanted in 50 patients in the aortic position between March 1994 and May 1995. Echocardiograms were performed in all patients before hospital discharge, at 3 months (41 patients), and at the end of first postoperative year (12 patients). The mean age was 69.8 +/- 5 years (range, 58 to 82 years). Eighty-four percent of patients presented with aortic stenosis and 16% had a combined lesion. Additional cardiac procedures were performed in 21 patients. RESULTS: Aortic cross-clamp time was 72 +/- 19 minutes, and bypass time was 97 +/- 28 minutes. There were three in-hospital deaths, and 2 patients died within the first postoperative year. Predischarge echocardiography demonstrated excellent hemodynamics, with a mean gradient of 20 +/- 8 mm Hg and no or trivial aortic insufficiency in 45 patients. One patient had moderate aortic insufficiency. At first follow-up 36 patients (90%) were in New York Heart Association class I and 4 patients were in class II. Echocardiography showed no evidence of valve failure or degeneration (mean gradient, 17 +/- 5mm Hg; aortic insufficiency = grade 0 [trivial] in 35 patients, grade II in 3 patients, and grade III in 1 patient). Similarly, no degeneration or valve failure with increasing aortic insufficiency was seen in the patients studied at the end of the first postoperative year. CONCLUSIONS: These results demonstrate that an autologous tissue cardiac valve can be manufactured in the operating room without significant additional operating time. Intraoperative testing minimizes the risk of primary failure with aortic insufficiency. Short-term results are encouraging with good hemodynamic performance of the valve and no signs of degeneration. However, long-term durability needs to be demonstrated.

Aged↗

Prognostic value of urokinase plasminogen activator and plasminogen activator inhibitor-1 in renal cell cancer.

PURPOSE: Urokinase type plasminogen activator and its inhibitor plasminogen activator inhibitor are associated with invasion and formation of metastases in tumors. In a prospective study urokinase and plasminogen activator inhibitor-1 content in renal cell cancer and benign renal tissue was correlated with the traditional factors of TNM staging and grading as well as ploidy and actual clinical outcome of the patients. MATERIAL AND METHODS: A total of 152 patients, who underwent transperitoneal tumor nephrectomy for renal cell cancer, was followed for a mean of 23.9 months. Urokinase and plasminogen activator inhibitor-1 from the tumor tissue and corresponding benign renal tissue were quantified from detergent extracted tissue samples (1% triton-X = 100 in TBS) and measured with an enzyme-linked immunosorbent assay. RESULTS: Urokinase content correlated with the development of distant metastases (log rank 4.32, p = 0.037). Cutoff value was 0.84 ng/mg. A group of 11 patients were considered to be at high risk for metastases (9 events) based on urokinase greater than 0.84 ng/mg., while 94 patients were considered to be at low risk (5 events) with urokinase less than 0.84 ng/mg. Plasminogen activator inhibitor-1 significantly correlated with the prevalence of distant metastases (log rank 5.17, MO, 10.04 versus M1, 23.79, p = 0.02) and the development of new metastases postoperatively (MO, 10.85 versus M1, 27.36, p = 0.001). Cutoff value was 12 ng/mg. protein. A group of 41 patients were considered at high risk for relapse (6) based on plasminogen activator inhibitor-1 greater than 12 ng/mg. protein compared to 55 patients with plasminogen activator inhibitor-1 less than 12 ng/mg. protein with only 1 relapse during followup. CONCLUSIONS: Plasminogen activator inhibitor-1, the specific inhibitor of urokinase is a strong and independent prognostic factor in predicting early relapse of renal cell carcinoma. High and low risk groups for disease-free survival can be discriminated by plasminogen activator inhibitor-1 antigen content in the tumor tissue.

Carcinoma, Renal Cell↗

Pharmacodynamic effects of St. John's Wort on rat intracerebral field potentials.

Two extracts of St. John s Wort were compared with respect to their action on in vivo monitored field potentials from four brain areas of the freely moving rat. Quantitative assessment of the drug action revealed a late onset (3 to 4 hours after oral application) and main effects on the frontal cortex. Changes consisted in electrical power alterations reminiscent of the action of antidepressive and/or analgesic drugs. Particular frequency bands affected first line were alpha1 and alpha2, which in some way are related to serotonergic and dopaminergic transmission. From this it is concluded that St. Johns Wort could be used for the indication of depression with predictable success. The extract labeled "K" turned out to be superior especially after repetitive application and could thus far be used for further studies.

Action Potentials↗

[DMSO in patients with active gonarthrosis. A double-blind placebo controlled phase III study].

BACKGROUND: For the patient, the most important aspect of gonarthrosis is pain and the associated impairment of movement.-- METHOD: In a randomized, placebo-controlled, double-blind study involving 112 patients (56 in each of the two groups test substance and placebo) the efficacy and tolerability of DMSO gel 25% applied over a period of three weeks were investigated in comparison with placebo. In addition to an assessment by the doctor of pain under loading while going about daily activities, rest pain, pain on palpation and of loss of mobility, the patient also kept a pain diary.-- RESULTS: In comparison with the gel base used as placebo, percutaneous treatment with DMSO proved to have a clinically relevant analgesic effect on the intensity of loading pain during everyday activities (p = 0.019). A positive effect of DMSO was also seen for pain intensity at rest (p = 0.015) and pressure pain (p = 0.029). The pain diary also reflected these observations. No serious adverse events or changes in laboratory values were observed.

Administration, Topical↗

Aortic valve replacement: is the stentless xenograft an alternative to the homograft? Early results of a randomized study.

From November 1992 to October 1993 we randomized 101 patients over 60 years of age undergoing elective aortic valve replacement, with or without concomitant coronary artery bypass grafting, to receive either a cryopreserved aortic or pulmonary homograft (n = 38) or a stentless porcine aortic valve xenograft (Edwards Prima 2500) (n = 63). The majority of all valves (92%) were inserted freehand in the subcoronary position. Six homografts (16%) were implanted as a free-root replacement and two xenografts (3%) were used as a mini root. There were four in-hospital deaths (4%), three in the homograft group and one in the xenograft group (homograft, 7.9% versus xenograft, 1.6%; p = not significant). Forty-one patients were followed at 3- to 6-month intervals for 9 +/- 2 months (3 to 14 months) and valve pathology was assessed routinely by means of color flow Doppler echocardiography. Two patients in the homograft group developed new aortic insufficiency grade II; all others remained with trivial or no valve incompetence. The mean gradient remained unchanged to immediate postoperative measurements (homograft, 5 +/- 1 mm Hg versus xenograft, 11 +/- 4 mm Hg; p < 0.001). Despite a slightly higher transvalvular gradient, xenografts achieved excellent initial results when compared to homografts. Ease of implantation and freedom from thromboembolism indicate that xenografts can be an acceptable alternative to homografts, particularly in older patients with small aortic annuli. Long-term studies assessing the durability of the xenograft are necessary for final evaluation.

Aged↗

Negotiating ureteral stenoses and kinks with a hydrophilic wire.

Negotiating a tortuous or obstructed ureter with a wire can be time-consuming and sometimes tiring. The principle of using a slippery floppy wire and then replacing it with a stiff wire through a 5-french open-ended ureteral catheter yields a high success rate. The ureteral catheter can be used for a radiocontrast study and allows access for a 0.035 'coaxial wire', which can be used as a guide wire for a single or double J stent.

Humans↗

Internally concealed cocaine: analytical and diagnostic aspects.

Thirty persons arrested at Frankfurt airport for smuggling internally concealed cocaine in 1993/1994 were investigated. An X-ray examination (in all 30 cases), immunochemical examination of urine (in 27 cases) and of saliva (in 20 cases) was performed in parallel. An X-ray examination gave positive results in all examined persons. EMIT cocaine metabolite assay (cut off 300 ng benzoylecgonine (BE)/mL) was positive in eight urine samples. After reducing the cut off to 150 ng BE/mL urine, eleven samples were classified as positive. The results were confirmed by means of chromatographic determinations. These findings showed limited role of immunological examination of urine as a screening test in suspected smuggling of internally concealed drugs. All saliva samples showed negative immunochemical results. The number of concealed containers ranged from 44 to 135 per person. The amount of cocaine hydrochloride found in particular cases ranged from 242 to 1050 g net weight, divided into containers weighing from 5.7 to 13.8 g. Drug packages were obviously machine-made. The packages smuggled by a particular person were uniform. However, a distinct interpersonal variability in drug packages was observed, in regard to the number of protective layers (4-7), size, weight, and cocaine purity. This may be helpful for the identification of production site. The leaching of cocaine from selected containers was investigated in a stirring bath and was independent of the conditions applied.

Adult↗

[Symptomatic bradycardia with amiodarone in patients with pre-existing conduction disorders].

Amiodarone has been shown to improve survival in patients with impaired left ventricular function and ventricular trachyarrhythmias. The clinical applicability, however, is limited by numerous often serious adverse effects. 70 patients receiving the treatment with amiodarone for ventricular tacharrhythmias were investigated regarding the development of symptomatic bradycardia. Group 1 consisted of 25 patients with preexisting conduction disorders, 5 had first degree heart block, 10 had right bundle branch block, and 7 had left bundle branch block on electrocardiographic examination. The 3 remaining patients showed asymptomatic sinus node dysfunction defined as sinus arrest or sinuatrial block. Amiodarone caused symptomatic bradycardia in 6 of the group 1 patients (II degrees-III degrees AV block in 3 patients with preexisting I degree AV block or right bundle branch block; intermittent sinus arrest or SA block in the 3 cases with previous sinus node dysfunction). 45 patients had no conduction disorders before the administration of amiodarone (group II). None of these patients developed symptomatic bradycardia. The difference to group I was significant (p < 0.0005). Thus, patients with preexisting conduction disorders have a substantial risk of developing symptomatic bradycardia under amiodarone therapy, with an incidence of 24% in group I patients of our collective.

Aged↗

Detection of aneuploid cells in acute lymphoblastic leukemia with flow cytometry before and after therapy.

We have evaluated the proliferative activity and DNA content of immunophenotyped hematopoietic cells applying flow cytometry. After indirect immunofluorescence the cell membrane was permeabilized for propidium iodide staining of DNA. Compared with single parameter detection of DNA content this method has more certainty in the determination of aneuploidies in lymphatic leukemia cells. Immunophenotyped residual normal hematopoietic cells were used as an internal standard. If this method was tested for evaluation of therapeutic effects after chemotherapy greater sensitivity in detection of minimal residual disease was observed than when using microscopic evaluation or single parameter DNA analysis in cases of aneuploid lymphoblastic leukemias.

Aneuploidy↗