PubMed Health⌕ Search

Biomedical subjects

G Engel

Publications and source records attributed to G Engel.

At least 19 recordsLinked to original sources
PubMed2004

Replacement therapy with levothyroxine plus triiodothyronine (bioavailable molar ratio 14 : 1) is not superior to thyroxine alone to improve well-being and cognitive performance in hypothyroidism.

OBJECTIVES: There is evidence from recent controlled clinical studies that replacement therapy of hypothyroidism with T4 in combination with a small amount of T3 may improve the well-being of the patients. As the issue is still the subject of controversial discussion, our study was assigned to confirm the superiority of a physiological combination of thyroid hormones (absorbed molar ratio 14 : 1) over T4 alone with regard to mood states and cognitive functioning. DESIGN AND PATIENTS: After a run-in period with the T4 study medication for 4 weeks, a controlled, randomized, double-blind, two-period (each 12 weeks), cross-over study without washout between the treatment periods was performed in 23 hypothyroid patients (three males, 20 females, age 23-69 years, 21 subjects after surgery/radioiodine, two with autoimmune thyroiditis) to compare the effects of the previous individual T4 dose (100-175 micro g) with a treatment in which 5% of the respective T4 dose was substituted by T3. MEASUREMENTS: Standard hormonal characteristics and standardized psychological tests to quantify mood and cognitive performance were measured after the run-in period and at the end of each treatment period. In 12 subjects, the concentration-time profiles of fT3 and fT4 were compared after the last administration of the respective study medication. TSH, fT3 and fT4 were measured with immunological assays. CLINICAL RESULTS: Replacement therapy with T4 and T4/T3 was not different in all steady-state hormonal, metabolic and cardiovascular characteristics except for TSH, which was more suppressed after T4/T3. The efficacy of replacement therapy with the T4/T3 combination was not different from the T4 monotherapy with regard to all psychological test scores describing mood and cognitive functioning of the patients. Mood was even significantly impaired by the T4/T3 combination in eight subjects, with TSH < 0.02 mU/l, compared to patients with normal TSH (Beck Depression Inventory: 8.25 +/- 5.01 vs. 4.07 +/- 5.60, P = 0.026). PHARMACOKINETIC RESULTS: The area under the concentration-time curve (AUC(0-8h)) of fT3 was significantly higher after T4/T3 compared to the T4 monotherapy (42.8 +/- 9.03 pmol x h/l vs. 36.3 +/- 8.50 pmol x h/l, P < 0.05) and was significantly correlated to serum TSH (r(s) = -0.609, P < 0.05). After T4/T3, patients with a history of Graves' disease or autoimmune thyroiditis had significantly higher serum trough levels of fT3 whereas the fT4 concentrations were significantly lower in patients with a nonautoimmune background. CONCLUSION: Replacement therapy of hypothyroidism with T4 plus T3 does not improve mood and cognitive performance compared to the standard T4 monotherapy. There is even a higher risk of signs of subclinical hyperthyroidism associated with impaired well-being of the patients, which is clearly caused by significant fluctuations in the steady-state fT3 serum concentrations.

Adult↗
PubMed2002

[Recurrent hemoptysis as initial symptom of a thoracic angiomatosis in an adult patient].

HISTORY: A 24-year-old man presented with recurrent hemoptysis and decreased exercise capacity. DIAGNOSTIC FINDINGS: The chest radiograph demonstrated multiple disseminated pulmonary nodules. In addition the patient developed a hematopericardium with tamponade. The further diagnostic approach revealed an extensive thoracic angiomatosis affecting the lung and the heart. TREATMENT AND COURSE: Tumor resection could not be performed. A therapy with Interferon alpha-2a was initiated. After 3 month a significant regression of the pulmonary angiomatosis was documented. On the other hand the cardiac tumor showed no therapeutic response. CONCLUSION: Thoracic angiomatosis should be considered in the differential diagnosis of otherwise unclear hemoptysis or hematopericardium. Diagnosis intra vitamin requires an aggressive and invasive approach. Interferon alpha-2a is effective in palliative treatment of diffuse angiomatous diseases. But not all angiomatous processes respond to that therapy.

Adult↗
PubMed2001

Feasibility and reliability of rapid diagnosis of myocardial infarction.

BACKGROUND: Prevailing hospital practice dictates a protracted phase of observation for patients with chest pain to establish or exclude the diagnosis of myocardial infarction. Early diagnosis of acute myocardial infarction may improve patient care and reduce both complications and hospital costs. A study was performed to investigate the feasibility of early diagnosis of myocardial infarction within the first 9 hours of the hospital stay. METHODS: The records of all patients admitted with chest pain within one calendar year were analyzed. The timing of creatine kinase-MB (CK-MB) quantification was determined with reference to the initial phlebotomy (time 0). An enzymatic diagnosis of myocardial infarction was assigned if any determination of CK-MB exceeded the upper limit of normal, and the diagnosis of each patient at or before 9 hours (early diagnosis) was compared to the ultimate diagnosis at 14 to 24 hours (final diagnosis) beyond initial assessment. RESULTS: Of the 528 included patients, 523 patients (99.1%) had identical early and final diagnostic outcomes; 5 patients (0.9%) had conflicting results. An early diagnosis of myocardial infarction was assigned to 195 of the 528 patients (36.9%). Of these, 190 achieved the diagnosis within 9 hours (sensitivity 97.4%). The negative predictive value was 98.5%. CONCLUSION: Standard CK-MB mass measurements within 9 hours of arrival provided an accurate clinical assessment in > 99% of the cases. The high sensitivity and negative predictive values suggest that early diagnosis of myocardial infarction is feasible and reliable.

Aged↗
PubMed2000

Comparison of several approaches of therapeutic drug monitoring of cyclosporin A based on individual pharmacokinetics.

OBJECTIVE: The clinical outcome of patients after organ transplantation is correlated with cyclosporin A (CyA) exposure. It is generally accepted that the area under the concentration-time curve (AUC) provides a reliable means for drug exposure. However, in routine therapeutic drug monitoring (TDM) of CyA, trough levels are mostly used. Currently, a number of different new concepts of CyA-TDM, including approaches such as single, double or triple time-point and abbreviated AUC determinations, have been introduced. The purpose of this study was to compare the predictive value of the different strategies of TDM. METHODS: Calculations were based on 40 individual concentration time profiles after oral administration of CyA to patients who had been included into an ongoing prospective clinical trial. Non-compartmental analysis was used to calculate the AUC0-12h. Multiple linear regression was performed to describe the relationship between the different sets of blood concentrations and the respective AUC0-12h as well as to evaluate their predictive value regarding AUC. Predictive performance was assessed by prediction bias and prediction precision, which were estimated as the mean prediction error and root mean squared error, respectively. RESULTS: When comparing the various combinations of time points, it was found that one-point approaches showed the strongest differences with regard to the predictive value; the associated r2 values differed from 0.203 to 0.792. The two and three time-point approaches showed lower differences - r2 0.802-0.972. The four-point and five-point approaches (r2 0.942-0.982) were the strongest predictors for CyA AUC0-12h. Relative bias ranged from -27.7% to 63.8% and changed significantly when multiple-point predictors were used. In those cases, the predictive performance improved. Considering the predictive performance as well as the smallest bias and highest prediction precision, C3, C1 + C3, C1 + C3 + C6 and C1 + C2 + C3 + C6 were the best predictors. CONCLUSION: The results of this study indicate that in kidney transplant patients a clinically sufficient precise estimation of the CyA AUC is possible using two or three concentration time points.

Adult↗
PubMed2000

Can axillary dissection be avoided by improved molecular biological diagnosis?

Axillary dissection is presently a routine staging procedure in the management of breast cancer. The use of adjuvant systemic treatment is largely based on the diagnosis of axillary metastases. Routine axillary dissection leads to acute and chronic side-effects in a large proportion of patients. The sentinel node technique is presently explored with the aim of decreasing the need for standard axillary dissection. A complementary way forward is to analyse the primary breast cancer for molecular markers with prognostic significance with reference to the risk for metastatic capacity and thereby obtain a 'biological staging' and identify those patients in need of systemic adjuvant therapy. A large number of molecular biological factors have been shown to have prognostic significance in breast cancer e.g. c-erbB-2, p53, uPA, PAI-I and VEGF. This article reviews the expression of these and other factors in the primary breast cancers in relation to the risk for axillary and systemic metastatic disease, with the long-term aim of excluding routine axillary dissection.

Axilla↗
PubMed2000

[Diagnostic approaches in pleural effusion].

It is not easy to discover the underlying cause for pleural effusion. Over a quarter of the pleural effusions remain unexplained by indirect methods of examination such as chemical, cytological or bacterial tests. Thoracoscopy however, shows impressive results and can be conducted under simple conditions. Different statistical collections allow for the assumption that pleural effusions due to cardiac disease and malignant conditions occur equally often. They are followed in frequency by infection diseases and the often misjudged effusion with pulmonary embolism.

Humans↗
PubMed1999

Malignant Sertoli cell tumor of the ovary metastatic to the lung mimicking neuroendocrine carcinoma: report of a case.

A Sertoli cell carcinoma of the ovary with lung metastases mimicking neuroendocrine carcinoma is presented. Lung metastases frequently occur. Primary and secondary tumors may exhibit similar growth patterns and differentiating primary from secondary tumors may be troublesome. This process may be more difficult when metastases occur from a tumor in which metastases are uncommon and morphologically resemble only a small portion of the primary tumor. We report the case of a 52-year-old woman who underwent resection of a 4,550-g Sertoli cell tumor of the ovary. Histologically, in addition to the characteristic tubular pattern of growth, 5% of the tumor consisted of poorly differentiated areas with tumor cells in sheets, a high mitotic rate, and areas of necrosis. Eleven months after this surgery she presented at a different institution with multiple pulmonary nodules. Microscopic examination of a subsequently resected lung nodule showed histologic findings similar to those of the poorly differentiated areas of the ovarian tumor and initial immunohistochemical studies showed positive staining for cytokeratin, neuron-specific enolase, and focal positivity for synaptophysin. Without knowledge of the ovarian tumor the lung lesion was interpreted as large-cell neuroendocrine carcinoma. On review of the clinical history and comparison with the previous surgical material, however, both tumors showed similar light microscopy and immunohistochemical reactivity, and a final diagnosis of metastatic Sertoli cell tumor was made. Immunohistochemical staining for inhibin revealed weak positivity in the poorly differentiated areas of the ovarian tumor but not in the lung metastasis. This is one of the rare reports of ovarian Sertoli cell tumor metastasizing to the lungs and it emphasizes the importance of complete clinical histories, ancillary studies, appropriate sampling, and review of archival material in such unusual cases.

Carcinoma, Neuroendocrine↗
PubMed1999

Predictive value of serum S100B for monitoring patients with metastatic melanoma during chemotherapy and/or immunotherapy.

In the immunohistology of malignant melanoma the use of polyclonal antibodies against protein S100 is well established. Recently, it was shown that S100B, a subunit of the S100 protein family, is detectable in the serum of melanoma patients and correlates with the stage of the disease in patients with metastatic melanoma. In the present study, the first evaluation of a large number of treatment observations (n = 77) in 64 different patients during chemotherapy and/or immunotherapy for advanced metastatic melanoma (stage IV) is presented. All patients received treatment according to standardized protocols comprising 8 weeks of treatment followed by routine staging procedures to evaluate therapeutic outcome. In 13 patients with tumour enlargement after first-line therapy, a second-line treatment was subsequently given. S100B immunoradiometric assay (IRMA) tests were performed before, during and after treatment at scheduled time points. In the interim analysis at 4 weeks 29 of 37 (78%) patients with tumour progression during treatment showed a raised S100B level. In the final analysis at 8 weeks, 31 of these 37 patients (84%) demonstrated rising S100B values (P < 0.001). Patients who responded to treatment (stable or regressing metastatic disease) showed constant or declining S100B levels in 38 of 40 patients (95%) at the interim analysis, at 8 weeks this was further increased to 39 of 40 patients (98%; P < 0.001). Thus, the use of S100B for monitoring treatment is adequate in the majority of cases. Our observations are of great interest for therapeutic trials of adjuvant and palliative therapies as the rise of S100B levels might indicate that re-staging and/or changes in therapy strategies should be chosen.

Adult↗
PubMed1999

S100B protein detection in serum is a significant prognostic factor in metastatic melanoma.

The serum detection of S100B, a new melanoma marker, has shown clinical significance in early studies. The aim of our study of 1, 339 serum samples from 412 different melanoma patients and 107 control patients was to prove the prognostic value of serum S100B levels in melanoma patients at different stages of disease and at follow-up (median: 30 months). Using a cutoff level of 0.2 microgram/l S100B, 5 of 286 patients (1.7%) with primary tumors (stage I/II), 14/73 (19.2%) patients with locoregional metastasis (stage III) and 57/84 (67.9%) patients with advanced disease (stage IV) were S100B positive (statistically significant differences for stage I/II vs. III, I/II vs. IV, and III vs. IV, p < 0.001). The estimated overall survival time was significantly longer (p < 0.001) for patients with S100B values below 0.2 microgram/l compared to patients with elevated S100B levels (>/=0.2 microgram/l), which was independent of the stage of disease (I-IV). Regarding prognosis, we were furthermore able to distinguish different subgroups among stage III and IV patients using S100B serum levels (p < 0.01). Patients with different cutaneous non-melanoma diseases served as S100B-negative controls. S100B serum evaluations using the Sangtec(R)100 IRMA are highly specific and sensitive for the detection of metastatic melanoma. S100B has been shown to be a relevant prognostic factor for survival in a study with a large sample size of melanoma patients including close follow-up evaluations.

Adult↗
PubMed1998

Structure of a genome region of the Lactobacillus gasseri temperate phage phiadh covering a repressor gene and cognate promoters.

By sequencing the DNA regions which flank the intG gene encoding integrase of the temperate Lactobacillus (Lb.) gasseri bacteriophage phiadh, a continuous sequence of 6590 bp was established. It encompasses five newly identified ORFs, of which four are located upstream, and one (orfC) downstream of intG. Proteins corresponding to the expected products of the intG upstream coding regions, orfA (33 kDa), orf2 (14 kDa), rad (12.1 kDa), and tec (7.9 kDa), were identified by in vitro expression of subcloned DNA fragments. Rad shares homology with transcription regulators, including SinR of Bacillus species and the repressor of phage phi105. The gporf2 is similar to predicted products of topologically equivalent coding regions of the Lactococcus lactis phage TP901-1 and the B. subtilis phage phi105. Promoters for the divergently oriented rad and tec genes were mapped within the 435-bp region between them and specify overlapping transcripts with extended 5'-untranslated sequences. As shown with lacZ fusions, Rad repressed transcription from the tec and rad promoters 20- and 5-fold, respectively. In Lb. gasseri, weak expression of cloned rad ws sufficient to mediate immunity towards phiadh.

Amino Acid Sequence↗
PubMed1998

Correlation between basic fibroblast growth factor immunostaining of stromal cells and stromelysin-3 mRNA expression in human breast carcinoma.

We examined the localization of basic fibroblast growth factor (bFGF) in a series of human breast carcinomas using immunohistochemistry. Staining was observed in tumour cells in 15 out of 54 (28%) tumours and in the adjacent stroma in 34 out of 54 (63%) tumours examined. No correlation was observed between positive staining of these two compartments. The relationship between bFGF staining and expression of the metalloprotease stromelysin-3, and between bFGF and microvessel density, was examined. A statistically significant correlation (P < 0.003) was observed between bFGF staining of the stromal compartment and high expression of stromelysin-3 (ST-3; MMP-11) metalloprotease mRNA by stromal cells. In contrast, no correlation was observed between bFGF and intratumour microvessel density (IMD). These results raise the possibility that bFGF may be involved in the induction of stromelysin-3 mRNA expression in breast cancer stroma.

Breast Neoplasms↗
PubMed1998

Stromelysin-3 mRNA expression in dysplasias and invasive epithelial cancer of the larynx.

Matrix metalloproteinases are believed to play an important role in tumor progression, invasion and metastasis. In order to investigate if the expression of stromelysin-3 (ST3) mRNA could add prognostic information concerning invasive laryngeal cancer and/or be indicative of a high risk for tumor progression in laryngeal dysplasias ST3 expression was analyzed by in situ hybridisation of formalin fixed paraffin embedded laryngeal specimens. Furthermore, all specimens underwent image cytometry (ICM) DNA analysis, and, p53 immunostaining. Invasive epithelial cancer, both localized (T1, T2) cancers, cured, as well as not cured, by radiotherapy, and cases with regional lymph node metastases were studied. Furthermore, high grade and low grade dysplasias, selected for rapid, slow and non-progression, as well as non-neoplastic inflammatory lesions were investigated. Expression of the ST3 gene was found in 9 out of 14 (64%) invasive cancer lesions, and in 3 out of 10 (30%) dysplasias, thus indicating that ST3 expression correlates to tumor progression. The ST3 positive laryngeal cancer lesions displayed a higher degree of DNA aberration than the ST3 negative lesions thus suggesting that ST3 positivity could indicate highly malignant tumors. Of the three ST3 positive dysplasias, the first progressed rapidly to cancer in situ with suspected microinvasion. The second ST3 positive dysplasia progressed to invasive cancer within five months. The third ST3 positive dysplasia had been radically excised and hereby cured. All but one of the dysplastic lesions showed p53 immunoreactivity, and all dysplasias exhibited aneuploid cells. ST3 expression appears to be a late event in the multistage process of carcinogenesis and could prove useful as an indicator of dysplasias with imminent risk for progression to invasive cancer.

Humans↗
PubMed1998

Interferon- and streptolysin O-induced activation of protein kinases and inhibition of cytochrome P450-dependent monooxygenases in rats.

Immunostimulants known to initiate cytokine production were found to decrease the activity of hepatic microsomal drug oxidative enzymes but to activate protein kinase C (PKC). The present study investigated the effects of immunostimulating doses of rat interferon-gamma (IFN, 670,000 units i.p.) and streptolysin O (SLO, 100 HU/kg i.v. for 5 days) on hepatic soluble, membrane-bound and nuclear PKC, 7-ethylresorufin-O-deethylase (EROD) and 7-pentylresorufin-O-deethylase (PROD) in male Wistar rats. The SLO- and IFN-mediated decrease of EROD and PROD activity was associated with a characteristic activation of the hepatic and spleenic PKC. In SLO- and IFN-treated animals activities of the cytosolic, membrane-bound and nuclear PKC were significantly higher than in respective controls. Our results suggest that a decrease in hepatic cytochrome P450 content as well as the decrease in the EROD and PROD activities are inversely related to the function of PKC.

Animals↗
PubMed1997

Distribution of stromelysin-3 mRNA transcripts and microvessels in human breast carcinomas.

Several proteinases, implicated in tumor invasion, are expressed in fibroblastic cells surrounding neoplastic cells, and are believed to be induced by paracrine stimulation. Such stimulation, by the local release of angiogenic factors, is also responsible for the induction of new capillary blood vessels, a crucial aspect of tumor growth and metastasis. We have here compared the expression of a matrix metalloproteinase, stromelysin-3 (ST3), with the distribution of tumor microvessels in invasive breast carcinomas. The highest level of ST3 mRNA in each tumor was recorded and compared to the highest microvessel density. No correlation between these two parameters was observed by analysis of 63 tumors. Detailed examination of 19 individual tumors did not reveal any correlation between the distribution of ST3 mRNA and microvessels. In the material studied here, ST3 expression was observed to correlate with long-term survival of the patients, whereas microvessel density did not correlate.

Breast Neoplasms↗
PubMed1997

The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine.

AIMS: Clozapine (CLZ), an atypical neuroleptic with a high risk of causing agranulocytosis, is metabolized in the liver to desmethylclozapine (DCLZ) and clozapine N-oxide (CLZ-NO). This study investigated the involvement of different CYP isoforms in the formation of these two metabolites. METHODS: Human liver microsomal incubations, chemical inhibitors, specific antibodies, and different cytochrome P450 expression systems were used. RESULTS: Km and Vmax values determined in human liver microsomes were lower for the demethylation (61 +/- 21 microM, 159 +/- 42 pmol min(-1) mg protein(-1) mean +/- s.d.; n = 4), than for the N-oxidation of CLZ (308 +/- 1.5 microM, 456 +/- 167 pmol min(-1) mg protein(-1); n = 3). Formation of DCLZ was inhibited by fluvoxamine (53 +/- 28% at 10 microM), triacetyloleandomycin (33 +/- 15% at 10 microM), and ketoconazole (51 +/- 28% at 2 microM) and by antibodies against CYP1A2 and CYP3A4. CLZ-NO formation was inhibited by triacetyloleandomycin (34 +/- 16% at 10 microM) and ketoconazole (51 +/- 13% at 2 microM), and by antibodies against CYP3A4. There was a significant correlation between CYP3A content and DCLZ formation in microsomes from 15 human livers (r=0.67; P=0.04). A high but not significant correlation coefficient was found for CYP3A content and CLZ-NO formation (r=0.59; P=0.09). Using expression systems it was shown that CYP1A2 and CYP3A4 formed DCLZ and CLZ-NO. Km and Vmax values were lower in the CYP1A2 expression system compared to CYP3A4 for both metabolic reactions. CONCLUSIONS: It is concluded that CYP1A2 and CYP3A4 are involved in the demethylation of CLZ and CYP3A4 in the N-oxidation of CLZ. Close monitoring of CLZ plasma levels is recommended in patients treated at the same time with other drugs affecting these two enzymes.

Antibodies↗
PubMed1997

Reduction of non-steroidal anti-inflammatory drug induced gastric injury and leucocyte endothelial adhesion by octreotide.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) induce gastric ulcers. AIMS: To assess whether the somatostatin analogue octreotide prevents NSAID induced mucosal gastrointestinal damage in both animals and humans. The effect of octreotide on neutrophil adhesion to the endothelium was also evaluated. METHODS: Male Sprague-Dawley rats were pretreated either with saline (0.3 ml subcutaneously) or octreotide (0.001-1 ng/kg subcutaneously). After 30 minutes gastric ulcers were induced by the intragastric application of NSAIDs (20 mg/kg indomethacin, 200 mg/kg aspirin, 200 mg/kg ibuprofen, or 50 mg/kg diclofenac). Four hours later the rats were killed and gastric mucosal lesions were assessed by computed planimetry. To determine whether octreotide could prevent indomethacin induced injury in humans, 20 healthy volunteers were evaluated in a double blind, placebo controlled study. RESULTS: Octreotide prevented NSAID induced gastric mucosal lesions (p < 0.05). The dose response curve was U shaped and the most effective dose was 0.1 ng/kg. Leucocyte adherence in submucosal venules of the stomach was evaluated by in vivo microscopy. Octreotide (0.1 ng/kg subcutaneously) prevented indomethacin (20 mg/kg intragastric) induced leucocyte adherence in gastric submucosal venules (p < 0.05). Healthy human volunteers received 50 mg indomethacin orally thrice a day concomitantly with either an identical placebo or 0.01 microgram, 0.1 microgram, or 1 microgram octreotide subcutaneously thrice a day for three days. Injury was assessed by endoscopy. There was a negative correlation between the octreotide dose and injury score (p < 0.03 for gastric injury, p < 0.001 for duodenal injury). CONCLUSIONS: Octreotide protects the stomach from NSAID induced gastric injury, probably via its ability to reduce NSAID induced neutrophilic adhesion to the microvasculature. Octreotide also ameliorated indomethacin induced gastric and duodenal injury in humans.

Animals↗