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Biomedical subjects

F Heinrich

Publications and source records attributed to F Heinrich.

At least 19 recordsLinked to original sources

Carotenoids are decreased in biopsies from colorectal adenomas.

UNLABELLED: A lower intake of carotenoids is associated with an increased risk of colorectal cancer. In order to take advantage of the chemopreventive properties of carotenoids, it is necessary to determine carotenoid concentration at the target tissue. As early stages in the adenoma-carcinoma sequence of colorectal cancer might be susceptible to chemoprevention, we sought to determine carotenoid concentrations in biopsies from colorectal adenomas. METHODS: Biopsies from colorectal adenomas and non-involved mucosa were taken from seven patients. For controls, biopsies were obtained from the ascending and descending colon of patients without polyps (n = 5). Concentration of carotenoids (alpha-, beta-carotene, lutein, lycopene, zeaxanthin, beta-cryptoxanthin) were determined by optimizing gradient HPLC-analysis. Results are expressed as pmol/microg DNA. RESULTS: Except for alpha-carotene, all carotenoids could reliably be detected in all specimens. In control patients carotenoid concentrations were highest in the ascending colon, being followed by the descending colon and non-involved mucosa from polyp-carriers. In colorectal adenomas all carotenoids were significantly reduced as compared to-non-involved mucosa (beta-carotene: 0.37 vs 0.19, P<0.03; lycopene: 0.34 vs 0.21, P<0.06, beta-cryptoxanthin: 0.14 vs 0.09, P<0.03, zeaxanthin: 0.18 vs 0.09, P<0.02; lutein: 0.18 vs 0.13,P <0.02). CONCLUSION: All carotenoids investigated are reduced in colorectal adenomas, suggesting that mucosal carotenoids could serve as biomarkers for predisposition to colorectal cancer. Moreover, anti-tumor activity exerted by carotenoids is limited due to mucosal depletion. We speculate that supplementation of a larger array of carotenoids might be beneficial for patients with colorectal adenoma.

Adenoma↗

[Necrobiotic xanthogranuloma , a cutaneous disorder associated with monoclonal gammopathy].

INTRODUCTION: Necrobiotic xanthogranuloma is a rare cutaneous disorder usually associated with monoclonal gammapathy. We describe two new cases. EXEGESIS: A 70-year-old patient was affected by a monoclonal gammopathy. She presented with a diplopia related to a retro-orbital tumor. The biopsy showed inflammatory lesions. Five years later, inflammatory xanthomatous skin lesions appeared. Biopsy specimens gave the diagnosis of necrobiotic xanthogranuloma. A 70-year-old woman was referred for inflammatory cutaneous lesions. Clinical, biological investigations and skin biopsies led to the diagnosis of cutaneous sarcoidosis associated with monoclonal gammopathy. Four years later, she developed a nephrotic syndrome. New skin biopsy specimens showed a necrobiotic xanthogranuloma. CONCLUSION: Necrobiotic xanthogranuloma is a systemic disease. It is a rare non-Langerhans cell histiocytosis characterized by frequent cutaneous and ophthalmologic lesions and associated with monoclonal gammopathy. To our knowledge, retro-orbital involvement has never been reported in necrobiotic xanthogranuloma. Treatment is difficult.

Aged↗

Improved method for rapid determination of vitamin A in small samples of breast milk by high-performance liquid chromatography.

Employing a short, potassium hydroxide (KOH) saponification (25 min) and rapid extraction with n-hexane-toluene (1:1) and a <4-min retention time, a convenient, rapid, accurate and precise determination of vitamin A in breast milk was developed. The recovery rate was 102.3 +/- 2.5% and the small relative standard deviation (intra-assay 1.9%, inter-assay 2.3%) resulted in high precision. The amount of breast milk needed is very low (1 ml) which makes the method suitable for the use in free field studies with large sample sizes. The simple extraction and separation steps allow a high throughput screening under routine laboratory conditions.

Chromatography, High Pressure Liquid↗

Determination of retinol, antioxidant vitamins and homocysteine in skin puncture blood.

For determination of the vitamin status via mass screening, simple and rapid methods are required. Additionally, blood samples should be obtained using simple and low invasive sampling techniques. To fulfill this existing methods have been modified to analyze retinol, tocopherols, beta-carotene, vitamin C and homocysteine in 20 microliters plasma. Blood samples were obtained via skin punctures. HPLC measurements were carried out with isocratic separation and precolumn derivatization. Intra and interday variation coefficients were below 8% and regression coefficients better than 0.99 for all measurements. The difference between venous and capillary samples were < 5%. In conclusion, the methods employed proved satisfactory for the determination of important nutritional parameters in blood samples obtained via skin punctures. These methods are therefore well suited for mass screening, especially under field conditions in developing countries.

Antioxidants↗

Biochemical but not clinical vitamin A deficiency results from mutations in the gene for retinol binding protein.

BACKGROUND: Two German sisters aged 14 and 17 y were admitted to the Tübingen eye hospital with a history of night blindness. In both siblings, plasma retinol binding protein (RBP) concentrations were below the limit of detection (<0.6 micromol/L) and plasma retinol concentrations were extremely low (0.19 micromol/L). Interestingly, intestinal absorption of retinyl esters was normal. In addition, other factors associated with low retinol concentrations (eg, low plasma transthyretin or zinc concentrations or mutations in the transthyretin gene) were not present. Neither sibling had a history of systemic disease. OBJECTIVE: Our aim was to investigate the cause of the retinol deficiency in these 2 siblings. DESIGN: The 2 siblings and their mother were examined clinically, including administration of the relative-dose-response test, DNA sequencing of the RBP gene, and routine laboratory testing. RESULTS: Genomic DNA sequence analysis revealed 2 point mutations in the RBP gene: a T-to-A substitution at nucleotide 1282 of exon 3 and a G-to-A substitution at nucleotide 1549 of exon 4. These mutations resulted in amino acid substitutions of asparagine for isoleucine at position 41 (Ile41-->Asn) and of aspartate for glycine at position 74 (Gly74-->Asp). Sequence analysis of cloned polymerase chain reaction products spanning exons 3 and 4 showed that these mutations were localized on different alleles. The genetic defect induced severe biochemical vitamin A deficiency but only mild clinical symptoms (night blindness and a modest retinal dystrophy without effects on growth). CONCLUSIONS: We conclude that the cellular supply of vitamin A to target tissues might be bypassed in these siblings via circulating retinyl esters, beta-carotene, or retinoic acid, thereby maintaining the health of peripheral tissues.

Adolescent↗

North Baden venous lysis trial (NBVL): multicentre prospective randomized phlebographically controlled trial on the effect of ultra-high versus conventional doses of streptokinase in fresh leg-pelvis venous thromboses.

Since no previous randomized comparison has been carried out between ultra-high and conventional dosage streptokinase therapy of fresh venous thromboses, the NBVL trial was carried out as a prospective, randomized, multicentre, phlebographically monitored comparison of the results and adverse effects of these two fibrinolytic treatment options. Using the normal exclusion criteria, 156 patients with a leg-pelvis venous thrombosis presumed to be a maximum of 14 days old were treated with 1.5 million U streptokinase/h for 6h daily (n = 77, group A) or conventional dosage with 100,000 U streptokinase per hour (n = 79, group B). There were 15 patients (eight in group A, seven in group B) who had to stop therapy prematurely, and eight patients (five in group A, three in group B) could not be evaluated because of incorrect monitoring times. The phlebograms were evaluated using IFP-C scores. These showed a reduction in the IFP score from 4.55 to 2.2 in the 64 patients in group A after a mean of 2.7 +/- 0.6 therapy cycles with administration of 24.4 +/- 5.7 million U streptokinase, i.e. 47% of the baseline value. The 69 patients in group B had a reduction in score from 4.2 to 2.93 after a mean of 3.7 +/- 1.2 days of treatment with administration of 8.6 +/- 3.3 million units, i.e. a fall of 30% in the baseline values (p = 0.007). There were 132 out of 281 completely occluded venous segments in group A (47%) and 81 out of 279 segments in group B (29%) that showed complete patency. Eight out of 27 three-segment occlusions in group A and only one of 26 in group B showed complete patency. The IFP score improved by 55% in the 45 men in group A, compared with only 30% in the 47 men in group B (p = 0.002). When both dosages are combined, men showed a greater improvement in IFP score than women (42 versus 29%; p = 0.02). The IFP score improved more in the 20 patients aged more than 60 years in group A than in the 19 patients aged over 60 years of age in group B (61 versus 20%; p = 0.003). No other significant differences in effect were seen on analysis of sub-groups and individual factors (sex, age, presumed age of thrombus and side of thrombosis). In the 77 patients in group A, haemorrhagic complications were less frequent than in the 79 patients in group B (22.1 versus 36.7%; p = 0.054), especially concerning urogenital haemorrhage (6.5 versus 22.8%; p = 0.004). Women were affected more frequently by haemorrhagic complications than men (35.2 versus 26.5%), and the 19 patients aged more than 65 years old were affected more than the 137 younger patients (21.1 versus 13.9%). There were no deaths, and clinically insignificant pulmonary emboli occurred three times. Ultra-high dosage streptokinase shows better and more rapid thrombolytic treatment for popliteal-femoral-iliac venous thromboses and causes fewer haemorrhagic complications than conventional dosage streptokinase. The better effect of ultra-high dosage can be observed particularly for three-segment occlusion as well as in male patients. In older patients, accurate diagnosis is required because of the higher rate of haemorrhagic complications.

Adult↗

Clinical evaluation of an immunoturbidimetric D-dimer assay in the diagnostic procedure of deep vein thrombosis and pulmonary embolism.

We investigated 128 patients with suspected deep vein thrombosis and 26 patients with suspected pulmonary embolism. Plasma cross-linked fibrin degradation products were measured instantly by a new rapid and fully quantitative immunoturbidimetric assay (Boehringer Mannheim) which recognizes the D-dimer epitope by antibody-coated latex particles. Diagnosis of deep vein thrombosis was established by either ascending venography (n = 105) or colour duplex ultrasound (n = 8), whereas for the exclusion of deep vein thrombosis only venography was accepted. The sensitivity/specificity for the diagnosis of deep vein thrombosis was 98%/44%. Patients with suspected pulmonary embolism were examined by pulmonary angiography (n = 19) or perfusion lung scanning alone (n = 6), if sufficient. One pulmonary embolism was diagnosed at post-mortem examination. For pulmonary embolism, sensitivity/specificity was 100%/50%. These findings indicate that the new immunoturbidimetric technique is as reliable as former ELISA methods and allows to rule out thromboembolic disorders. D-dimers showed a correlation to the extent of the deep vein thrombosis, proximal thrombosis producing higher D-dimer levels. Patients presenting immediately after the onset of symptoms were found to have higher D-dimers than patients examined after a few days. A quantitative D-dimer measurement thus seems to provide precious additional information of the duration and the extent of thromboembolic disease.

Adult↗

Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry.

OBJECTIVES: The present study investigated current management strategies as well as the clinical course of acute major pulmonary embolism. BACKGROUND: The clinical outcome of patients with acute pulmonary embolism who present with overt or impending right heart failure has not yet been adequately elucidated. METHODS: The 204 participating centers enrolled a total of 1,001 consecutive patients. The inclusion criteria were based on the clinical findings at presentation and the results of electrocardiographic, echocardiographic, nuclear imaging and cardiac catheterization studies. RESULTS: Echocardiography was the most frequently performed diagnostic procedure (74%). Lung scan or pulmonary angiography were performed in 79% of clinically stable patients but much less frequently in those with circulatory collapse at presentation (32%, p < 0.001). Thrombolytic agents were given to 478 patients (48%), often despite the presence of contraindications (193 [40%] of 478). The frequency of initial thrombolysis was significantly higher in clinically unstable than in normotensive patients (57% vs. 22%, p < 0.001). Overall in-hospital mortality rate ranged from 8.1% in the group of stable patients to 25% in those presenting with cardiogenic shock and to 65% in patients necessitating cardiopulmonary resuscitation. Major bleeding was reported in 92 patients (9.2%), but cerebral bleeding was uncommon (0.5%). Finally, recurrent pulmonary embolism occurred in 172 patients (17%). CONCLUSIONS: Current management strategies of acute major pulmonary embolism are largely dependent on the degree of hemodynamic instability at presentation. In the presence of severe hemodynamic compromise, physicians often rely on the findings of bedside echocardiography and proceed to thrombolytic treatment without seeking further diagnostic certainty in nuclear imaging or angiographic studies.

Acute Disease↗

Association between thrombolytic treatment and the prognosis of hemodynamically stable patients with major pulmonary embolism: results of a multicenter registry.

BACKGROUND: Thrombolytic treatment has been shown to accelerate resolution of major pulmonary embolism and lead to a rapid improvement of right-side hemodynamics. However, the association between these favorable effects and the clinical outcome of patients who have no severe hemodynamic compromise at presentation remains unknown. METHODS AND RESULTS: The present multicenter registry included 719 consecutive patients with major pulmonary embolism according to clinical, echocardiographic, scintigraphic, and cardiac catheterization criteria. Symptom onset was acute (<48 hours) in 63% of patients. All patients were hemodynamically stable (ie, without evidence of cardiogenic shock) at presentation. Primary thrombolytic treatment (within 24 hours of diagnosis) was given to 169 patients (23.5%), whereas the remaining 550 patients were initially treated with heparin alone. Overall 30-day mortality was significantly lower in the patients who received thrombolytic agents (4.7 versus 11.1%, P=.016). Clinical factors associated with a higher death rate were syncope (P=.012), arterial hypotension (P=.021), history of congestive heart failure (P=.013), and chronic pulmonary disease (P=.032). However, only primary thrombolysis was found by multivariate analysis to be an independent predictor of survival (odds ratio for in-hospital death, 0.46; 95% confidence interval, 0.21 to 1.00). Patients who underwent early thrombolytic treatment had a reduced rate of recurrent pulmonary embolism (7.7 versus 18.7%, P<.001) but also a higher frequency of major bleeding episodes (21.9% versus 7.8%, P<.001). Cerebral bleeding occurred in 2 patients in each treatment group, and 1 patient in each group died of a bleeding complication. CONCLUSIONS: The results of our study suggest that thrombolysis may favorably affect the clinical outcome of hemodynamically stable patients with major pulmonary embolism.

Adolescent↗

[Early treatment of acute myocardial infarct: implementation of therapy guidelines in routine clinical practice, MITRA pilot phase].

The prognostic value of thrombolytics, aspirin, beta-blockers and ACE-inhibitors has been well documented in large clinical trials, but the application of these drugs in clinical practice is not known. MITRA is a multicenter study of 54 hospitals in a defined region in southwest Germany. The aim is to document actual clinical practice (pilot phase) and to establish an individually optimised prognostic therapy for acute myocardial infarction, considering only the absolute contraindications for each drug. In the pilot phase, 1303 consecutive patients with acute transmural myocardial infarction were enrolled. The median age was 66 years, the prehospital time was 2.7 hours. 47% had an anterior infarction. In the subgroup of patients without absolute contraindications, only 53.4% were treated with thrombolytics, 87.6% with aspirin, 37.1% with beta-blocker, and 17.4% with ACE-inhibitor. Out of these, patients were classified as "optimally treated" if they received thrombolysis, aspirin as well as beta-blocker. Patients were also included if any of these medications was withheld in the presence of absolute contraindications. Treatment was defined suboptimal, if the patients did not receive any of these three medications despite the absence of absolute contraindications. Only 29% (n = 383) received an optimal post-infarction therapy and 71% (n = 775) a suboptimal treatment. The univariate analysis revealed 10 variables influencing optimal therapy. In this subgroup patients were younger, they more often had clear ECG-findings or left bundle branch block, an anterior infarction, acute cardiac failure, AV-block, bradycardia, recent trauma or surgery (less then 2 weeks) and a severe chronic obstructive lung disease. The prehospital time was more often available. Early mortality after 2 days was 5.0% versus 9.3% in the suboptimal treated patients (OR: 0.5, CI: 0.30-0.86) the total inhospital mortality was 10.9% in the optimal versus 17.7% in the suboptimal group (OR: 0.6, CI: 0.38-0.84). In a multivariate analysis the parameter "optimal treatment" was found to be an independent predictor of the early (OR = 0.4; CI: 0.20-0.69) and the inhospital mortality (OR = 0.4; CI: 0.25-0.64). The following in-hospital events occurred: stroke 2.8%, reinfarction 12.9%, cardiac failure 21.5%, cardiogenic shock 10.4% and in-hospital mortality 18.1% (2-days mortality 9.5%). Pharmacological therapy for acute myocardial infarction is inconsistent with the recommendations suggested in recent clinical trials and needs to be individually optimised. Optimal treatment is an independent predictor of early and inhospital mortality.

Adrenergic beta-Antagonists↗

Treatment of deep vein thrombosis with low-molecular-weight heparins: a consensus statement of the Gesellschaft für Thrombose-und Hämostaseforschung (GTH).

Recent studies have led to a new concept for the management of deep vein thrombosis. The German Society on Thrombosis and Haemostasis decided to work up the clinical studies in this field published until June 1996 for a consensus statement. The consensus group concluded that (1) high-dose, APTT-controlled subcutaneous administration of unfractionated heparin is as effective as high-dose, APTT-controlled continuous intravenous infusion of unfractionated heparin (grade B recommendation); (2) the anticoagulation with heparin may start at day 1 or 2, overlapping with oral anticoagulants for 7 to 10 days (grade C recommendation); (3) high-dose subcutaneous low-molecular-weight heparins are almost as effective and safe as continuous intravenous infusion of unfractionated heparins (grade B recommendation); (4) no agreement was obtained for the other concomitant treatments of DVT, such as duration of bed rest, use of antiphlogistic drugs, whether LMW heparins are comparable, and whether outpatient treatment can be recommended using LMW heparins.

Anticoagulants↗

[Results of the North Baden Venous Lysis--NBVL--Study. Prospective phlebographically controlled randomized multicenter evaluation of ultra high versus conventional dose streptokinase in acute thrombosis of the leg and pelvic veins].

BACKGROUND AND AIM: The Nordbaden Multicentre Study on lysis of venous thrombosis was prompted by a lack of randomized studies comparing ultra-high and conventional-dose streptokinase therapy in fresh iliac and leg vein thrombosis. The aim was to compare prospectively the phlebographically monitored results of three courses of ultra-high dosed with those of a 5-day course of conventionally dosed streptokinase treatment and to record any side-effects of fibrinolysis. PATIENTS AND METHOD: 77 patients were randomized to ultra-high-dose streptokinase (group A), and 79 to conventionally-dosed streptokinase (group B) therapy. In 13 patients of group A and 10 of group B, no monitoring phlebography was possible--in 15 patients (9.6%) who broke off treatment prematurely, and in 8 (5.1%) who failed to keep their phlebography appointment. RESULTS: Detailed analysis of the phlebographic findings (main target criterion) on the basis of the IFP score revealed a decrease in the score from 4.55 to 2.41 (47%) for the 64 group A patients after a mean of 2.7 +/- 0.6 courses of treatment with administration of 24 +/- 5.7 million IU streptokinase, and from 4.2 to 2.93 (30%) for the 69 group B patients after a mean of 3.7 +/- 1.2 days of treatment with administration of 8.6 +/- 3.3 million IU (p = 0.007). Of the 281 totally occluded vein segments in group A, 132 (47%) were rendered fully patent, while this was true of 81 (29%) of the 279 total occlusions in group B. Of the 21 incomplete occlusions in each group, 10 in group A and 16 in group B became fully patent. Analysis of subgroups and individual factors showed that the re-establishment of patency in the 45 men in group A was better (55%) than in the 47 group B men (30%); while the women showed no inter-group difference there was an overall difference vis-a-vis the men (p = 0.02). In group A, patients aged over 60 showed better results (61%) than those of the same age in group B (20%) (p = 0.003). The presumably older thrombi were just as readily lysable as fresher ones. Among the 77 group A patients, side-effects occurred significantly less frequently than among the 79 group B patients. For the most part, side-effects were haemorrhage overall (22.1% vs. 35.7%) and urogenital bleeding in particular (6.5% vs. 22.8%); there were no deaths. Women bled somewhat more often than men (35.2% vs. 26.5%), and bleeding was more commonly in patients older than 65 years. CONCLUSIONS: 1. Ultra-high-dose streptokinase treatment of deep venous thrombosis (iliac, femoral, popliteal veins) is more effective (at least in males) and produces less bleeding than conventional doses. 2. Presumably older thromboses (8 to 14 days) are no less responsive to ultra-high dose streptokinase. 3. In view of the higher risk of bleeding in over-65-year-olds, the indication for fibrinolytic therapy must be considered with care.

Adult↗

[Clinical aspects, diagnosis and therapy of pulmonary embolism].

Pulmonary embolism is a frequent and malignant complication of other diseases. To consider this is the most important step. ECG, pO2/pCO2, chest X-ray are used for differential diagnosis; pulmonary embolism is directly confirmed by scintigraphy, echocardiography, pulmonary angiography and pulmonary artery catheterisation, supplemented by examination of lower venous system (sonography, phlebography). Small emboli should also be noted as a signal of dangerous recurrence. The choice of the therapeutic method (embolectomy, fibrinolysis, anticoagulation) depends on the severity of pulmonary embolism, available methods and present contraindications. Depending upon the severity and general condition of the patient, it may be necessary to disregard possible contraindications against therapeutic methods that may cause desobliteration. Anticoagulation is used as prophylactic method, in exceptional cases a blockade is applied to the vena cava inferior.

Diagnostic Imaging↗

Evaluation of plasma D-dimer in the diagnosis and in the course of fibrinolytic therapy of deep vein thrombosis and pulmonary embolism.

Blood samples were obtained from patients with deep venous thrombosis (DVT) or pulmonary embolism (PE) after angiographic confirmation as well as during fibrinolytic therapy with streptokinase. Plasma cross-linked fibrin degradation products were measured by a quantitative enzyme-linked immunoassay that recognizes the D-Dimer epitope. 24 patients with PE showed elevated D-Dimer levels (median; 25%-, 75%-quartile) (3,250 ng/ml; 1,270 ng/ml, 6,940 ng/ml) as well as 38 patients presenting with DVT (2,330 ng/ml; 1,760 ng/ml, 3,980 ng/ml). The sensitivity for the diagnosis of PE was 92%, for diagnosis of DVT 89% resp. 100%, depending on the cut-off limit. The D-Dimer level showed a correlation (r = 0.64) to the angiographically documented severity of PE quantified by the Miller's score, in contrast to DVT, where no such correlation could be found. During fibrinolytic therapy median levels rose from 3,020 ng/ml to 63,000 ng/ml within 8 hours and then fell within 6 days to 2,930 ng/ml. 10 patients with PE showed a good correlation (r = 0.72) between the reduction of Miller's score within 72 hours and D-Dimer 24 hours after the onset of therapy. In 17 patients with fibrinolytic treatment of DVT no correlation between D-Dimer and clot lysis could be found. These findings indicate that D-Dimer can provide additional information in the diagnostic procedure of suspected PE. During fibrinolytic therapy of PE with streptokinase, D-Dimer could serve as an early prognostic parameter of successful thrombolysis.

Biomarkers↗

[New developments and findings in the field of opiates, opioids, opiate receptors and complete and partial opiate antagonists].

The historical development of the application of opiates is reviewed. After the detection and localization of opiate receptors in 1973, the clinical application of these substances has been scientifically and systematically developed. The function of the opiate system, the theory of opiate receptors, the opioid peptides, substance P as well as different opiates and analgesics are discussed in detail. The international trend in recent research efforts is aimed at finding a kappa-receptor specific opioid. The aim is to develop a selectively analgesic-acting opioid without respiratory depressant and addictive effects and without cardiovascular and excitative side-effects. Although major progress has been made in synthesizing the partial opiate agonist and opiate antagonist nalbuphine ++ (nubain), it has not yet been possible to develop a drug completely corresponding to ideal concepts.

Endorphins↗