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D Branscheid

Publications and source records attributed to D Branscheid.

At least 37 records · Page 2Linked to original sources

Passive sensitization of human airways increases responsiveness to leukotriene C4.

Passive sensitization of human airways in vitro causes increased responsiveness to histamine and induces specific immunoglobulin (Ig)E-dependent contractile responsiveness to allergen. Leukotrienes (LTs) and, to a lesser extent, histamine are the major mediators of allergen-induced contraction. Since it is unclear whether passively sensitized airways are also hyperresponsive to cysteinyl leukotrienes, this study investigated the effect of passive sensitization on LTC4-, in addition to histamine- and allergen-induced contractions in vitro. Bronchial rings from nine nonatopic patients were sensitized overnight with serum containing high levels of total IgE (>250 U x mL(-1)) and allergen-specific IgE against Dermatophagoides farinae (fluorescence allergosorbent test) (FAST class > or =3). The potency (-log10 of the mediator concentration causing a half maximal response (pEC50) of histamine was significantly increased in serum-sensitized tissues compared to nonsensitized controls ((mean+/-SEM) pEC50 5.20+/-0.27 versus 5.64+/-0.18; p=0.02) and maximal contractions were enhanced (877+/-47 versus 543+/-51 mg; p<0.0001). Similarly, the potency of LTC4 was significantly increased in sensitized compared to nonsensitized bronchial rings (pEC50 9.37+/-0.20 versus 8.66+/-0.26; p=0.004); maximal contractions were also enhanced (811+/-57 versus 361+/-86 mg; p<0.0001). These data demonstrate that passive sensitization of human airways induces an increase not only in histamine but also in leukotriene responsiveness. Therefore, it might be speculated that allergen responses in sensitized airways are effected through a combination of increased mediator release from inflammatory cells and increased responsiveness of airway smooth muscle.

Adult↗

Effects of a selective PDE4 inhibitor, D-22888, on human airways and eosinophils in vitro and late phase allergic pulmonary eosinophilia in guinea pigs.

The actions of a novel selective inhibitor of type 4 cyclic nucleotide phosphodiesterase (PDE4), D-22888, on human airway smooth muscle tone and human eosinophil respiratory burst in vitro and bronchoalveolar eosinophilia in allergen-challenged sensitized guinea pigs in vivo were assessed. D-22888 was a selective inhibitor of PDE4, exhibiting an IC50 against human neutrophil PDE4 of 0.15 microM, compared to IC 50 values of 4.4 microM and 1.1 microM for human platelet PDE3 and PDE5, respectively. D-22888 relaxed inherent tone in human bronchial rings in a concentration-dependent manner with an IC50 of 5.0 microM (geometric mean, 95% ci 3.0-8.4 microM) and also caused a concentration-dependent inhibition of opsonized zymosan-induced superoxide anion generation by human eosinophils with an IC50 of 3.1 microM (1.0-9.2 microM). Treatment of actively sensitized guinea pigs with single oral doses of D-22888 2 h before or 4 h after challenge reduced bronchoalveolar lavage (BAL) eosinophil numbers, 24 h after aerosol allergen challenge, by 48% and 73% at 10 mg/kg and 30 mg/kg, respectively, 2 h pre-challenge and 68% at 30 mg/kg 4 h post-challenge. Chronic twice-daily oral dosing with D-22888 for three days caused inhibition of 24 h post-challenge BAL eosinophilia, amounting to 88% at 30 mg/kg. These in vivo actions were comparable with those achieved with other selective PDE4 inhibitors and with the corticosteroid, dexamethasone. We conclude that D-22888 exerts actions on airway smooth muscle and eosinophil recruitment and activation that suggest that D-22888 may be a promising new drug for use in the treatment of allergic obstructive airways>> diseases such as bronchial asthma.

3',5'-Cyclic-AMP Phosphodiesterases↗

[Surgical therapeutic strategy in non-small-cell bronchial carcinoma].

For localized, non-small cell carcinomas (stages I and II) surgery is the treatment of choice because these lesions usually can be excised completely. The choice of the surgical procedure--lobectomy, pneumonectomy, segmental or sleeve resection--depends on the extent of malignant disease and the patients functional status. The procedure of choice is usually that which will encompass all existing disease and provide maximum conservation of normal lung tissue. On occasion, stage III disease may present borderline cases for surgery. Indications are based on existing or imminent complications in advanced locoregional tumor growth. Localized chest-wall or pericardium invasion, superior sulcus tumors, limited mediastinal nodal involvement, and phrenic involvement are not absolute surgical contraindications. Each case must carefully be evaluated and individualised. This kind of tumor management requires sophisticated techniques. The primary aim is to achieve complete tumor resection and to avoid an exploratory thoracotomy or an incomplete surgical resection. The hilar and mediastinal lymph nodes have to be completely resected to ensure a real R0-resection. The presence of distant or extrathoracic metastasis is indicative of inoperability and a surgical procedure is an absolute contraindication. There is no proven place to date for debulking surgical procedures in lung cancer.

Carcinoma, Non-Small-Cell Lung↗

Preferential histiotypic expression of CD44-isoforms in human lung cancer.

The CD44 transmembrane glycoprotein is expressed in most adult tissues and in the majority of neoplasias. Due to alternative splicing, this cell adhesion molecule exists in multiple isoforms some of which have been associated with specific types of tumours as well as with increased tumour metastasis. In this study, we have looked at the level and type of CD44 expression in lung cancer which represents a histologically heterogenous form of cancer composed of small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC), the latter subgroup comprising adenocarcinoma (ADC), bronchio-alveolar carcinoma (BAC), large cell carcinoma (LCC), and squamous cell carcinoma (SCC). We analysed 20 lung cancer cell lines and 64 primary tumours by RT-PCR and immunohistochemical detection of the CD44 standard and variant protein isoforms. Our results suggest that (i) CD44 is expressed in all histologically distinct subsets of lung cancer with a tendency SCC > BAC > ADC > LCC > SCLC, (ii) expression of the CD44 isoforms v5, v7, v8, and, most notably that of CD44 exon v6, strongly correlates with tumours of squamous cell and bronchio-alveolar carcinoma origin, tumours which commonly exhibit a comparatively low metastasizing potential, and (iii) the expression of CD44 isoforms is independent from the tumour size and lymph node status at surgery, the proliferative status of the tumour cell population (Ki67 antigen expression) and the histopathological grading (G1 to G3). Only non-differentiated tumours (G4), which were restricted to SCLC and LCC samples revealed markedly reduced CD44 standard and isoform antigen. In conclusion, our data point to a clear histiotype-related pattern of CD44 variant expression preferentially that of CD44v6 in SCC and BAC.

Adenocarcinoma↗

Steroid-hormone receptors in cell lines and tumor biopsies of human lung cancer.

Female gender is a significant independent favorable prognostic factor in lung cancer. To study the possible role of sex hormones in lung cancer, the expression of sex-steroid receptors and the glucocorticoid receptor was investigated in 29 lung-cancer cell lines stemming from small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) by means of immunocytochemistry, ligand-binding assays and RNA expression via polymerase chain reaction. In at least 2 methods of investigation, NSCLC cell lines showed a low expression of estrogen receptor in 6, progesterone receptor in 13 and androgen receptor in 12 out of 17 cases examined; sex-steroid-receptor expression was virtually absent in SCLC cell lines. The glucocorticoid receptor was expressed in all 29 cell lines studied. Additionally, 52 tumor samples from primary lung cancer were investigated for their receptor expression by means of immunohistochemistry. Among patients with primary lung-cancer sex-steroid-receptor expression in tumor biopsies was detected most frequently in female patients (in 69% of 16 cases, vs. 42% of 36 tumors from men) and in patients with adenocarcinoma. Further research will focus on these subgroups. Immunohistology is a feasible method of studying steroid-receptor expression in lung cancer.

Base Sequence↗

[Surgery of lung metastasis--indications, results and prognostic factors as an interdisciplinary concept].

Surgical therapy of lung metastases nowadays is an established procedure. The operation's purpose is the radical and therefore potential curative resection. Beside there are diagnostic and palliative indications. Beside there are diagnostic and palliative indications. Median sternotomy is the standard approach for revision of both lungs even in unilateral seeming disease. Preoperative staging is not reliable concerning number and extension of metastases. From 1972 to 1991 843 operations for lung metastases were carried out in 729 patients in the surgical department of the "Thoraxklinik Heidelberg-Rohrbach". 30-day-mortality amounted to 2.9%, 5-year-survival-rate was 33% overall from date of metastases resection. The best results were achieved in testicular cancer with 67% 5-years-survival-rate, poorest survival was observed in melanomas with 12% 3-years-survival. Beside the primary tumor and partly dependent on it several prognostic factors were relevant: radicality, sarcoma vs carcinoma in favour of carcinomas, disease-free interval, type of resection, thoracic lymphnode involvement. As figured out by multivariate analysis the prognostic influence of the factors varies considerably due to the kind of primary tumor. Surgery of lung metastases is part of an interdisciplinary oncological therapeutical concept and offers a prolonged survival to most of the patients and the possibility of cure to some. Even if prolongation of life is not feasible an improved quality and therefore a good palliation is obtained.

Adolescent↗

[Surgery for bronchial carcinoma with mediastinal lymph node involvement].

Or the 3000 patients analyzed in the prospective bronchial carcinoma field study, 1086 were operated between 1984 and 1989. Complete systematic mediastinal lymphadenectomy was performed in 661 patients to assess the PTNM stage as exactly as possible, and to improve prognosis. Lymphadenectomy removes all hylarand mediastinal lymph nodes. Although the operation is technically quite easy on the clearly structured right side, it is more difficult on the left side due to the aortic arch and its branches. The lymph nodes of the upper mediastinum of the left and right side can be completely dissected by mobilizing the aortic arch with the left subclavian artery. In contrast to what is frequently assumed, the histological findings indicate that there is no general pattern of metastatic spread in the lymph nodes. The metastases can leave out varying numbers of lymph nodes craniad as well as caudad. For this reason, the lymph nodes have to be completely resected to ensure a real R0-resection.

Female↗

Surgery for congenital malformations of the lung.

In the course of a survey conducted in 59 hospitals performing thoracic surgery, 14 hospitals supplied data that could be used for the study. Out of 1347 anomalies diagnosed 1343 were surgically treated, with a 30-day mortality rate of 0.3% (5 patients). In a retrospective study over a period of 10 years (1978-1988) we identified 198 anomalies out of a total of 6350 thoracotomies; so our percentage grading of pulmonary anomalies is supported by the data of the above-mentioned survey according to which cystic pulmonary malformations such as inhibition malformations, excess malformation and lobar emphysema represent a majority with 72.2% (survey 83%). Congenital anomalies of lung formation occurred in 23% of the patients of the survey and in 15% of our own patients. Therapy consisted of parenchyma-saving surgery, i.e. enucleation (n = 87), segmental resection (n = 65) and lobectomy (n = 63) with bronchoplastic reconstruction; there was no 30-day mortality. Adenomatoid-cystic malformation, lymphangiectasis, congenital lobar emphysema and stenosis of the tracheobronchial tree are often an indication for immediate surgical treatment in neonates. Solitary cysts, bronchiectasis, sequestration of the lung, an AV-fistula present with symptoms mostly between the ages of 20-40 and therefore were surgically treated secondarily.

Adolescent↗

[Pulmonary sequestration: use of MR-angiography].

The confirmation of the diagnosis of intralobar pulmonary sequestration usually requires angiographic demonstration of the systemic arterial supply, and venous drainage. Magnetic resonance angiography (MR angiography) is a new, non-invasive imaging modality for examinations of the vasculature. In this report we describe its successful application in intralobar pulmonary sequestration demonstrating the feeding systemic artery, including its intrapulmonary branching, and the type of the venous return.

Adult↗

Does ND-YAG laser extend the indications for resection of pulmonary metastases?

Surgery forms part of a combined oncological concept in the management of pulmonary metastases. The following questions are relevant for its role: Does survival depend on the type of primary tumor? Are there any prognostic factors? What are the limits on radical resection? We analyzed retrospectively 657 patients who had undergone 759 resections of pulmonary metastases between 1973 and 1990. After conducting in vitro and in vivo experiments with the non-contact neodymium aluminum garnet (Nd-YAG) laser with a generating and delivery power of 10-120 W at the site of operation for 0.1-9.9 s, we have treated 65 patients by laser resection and/or vaporization since January 1990. Our preferred surgical approach was median or transverse thoracotomy. The 5-year survival of all resected patients was 30%, ranging from 21% (soft tissue sarcoma) to 60% (testicular carcinoma). Statistically significant differences in prognosis were seen related to the type of primary tumor, the disease-free interval, the caval or portal type of metastatic spread, the number of metastases and the potential degree of radical resection. The potential degree of conventional radical resections (wedge, anatomical sub-/segmental) was negatively influenced by the number of metastases (n > 9: 79% "radical" surgery = 38% 5-year survival). Laser treatment allowed parenchyma-preserving resection in cases of metastases of more than 0.5 cm in diameter, and vaporization in smaller ones. Resection with the intention of achieving complete remission was possible in up to 72 unilateral metastases. The complication rate was comparable to conventional resections.

Female↗

Exposure of human lung fibroblasts to ozone: cell mortality and hyaluronan metabolism.

Exposure of cultures of human lung fibroblasts to 0.5 ppm ozone for 20 h resulted in a significant increase in cellular mortality by 29%; after exposure to 2.5 ppm ozone for 4 h, the increase amounted to 74%. A marked difference in sensitivity to ozone was observed between fibroblast lines from different individuals. This variability in resistance to ozone was more evident after exposure to 0.5 ppm ozone for 20 h, when compared with 2.5 ppm ozone for 4 h. In one fibroblast line, synthesis of hyaluronan was enhanced by exposure to 0.5 ppm ozone for 20 h. The concentrations of hyaluronan in culture media increased in experiments using different fibroblast cell lines, a phenomenon that was obvious both if cell numbers and combined protein concentrations of cells and media are selected as references for hyaluronan concentrations.

Cell Death↗

[Surgical treatment of carcinoid tumors of the intestine].

Carcinoid tumours arise from the neuroendocrine system and present a characteristic morphological picture. They occur in almost every organ, predilected sites are the appendix and the small intestine. Prognosis depends on the primary localization and tumour size. Carcinoids of the appendix and rectum are mostly small and thus have a good prognosis. Growth of bronchial, stomach and small intestinal carcinoids is aggressive and implicates a high percentage of metastatic disease. First choice therapy is the surgical removal of the tumour. Depending on tumour size surgical treatment includes fulguration, local excision and oncologic radical resection up to extended organ extirpation. Reoperation and repeated surgery have good chances to be successful concerning tumour remission and improvement of the carcinoid syndrome. Additive treatment comprises in particular somatostatin therapy and, in some cases, chemotherapy.

Appendiceal Neoplasms↗

Immunohistochemical localization of receptors for vasoactive intestinal peptide and substance P in human trachea.

BACKGROUND: Tissue sections of human cervical trachea were processed for immunohistochemical demonstration of receptors for substance P [using an anti-SP anti-idiotypic antiserum directed toward the ligand binding site of the receptor (Couraud J-Y, Escher ED, Regoli D, Imhof V, Rossignol B, Pradelles P. Anti-substance P anti-idiotypic antibodies: Characterization and biological activities. J Biol Chem 1985;260:9461-9; Couraud J-Y, Maillet S, Grassi J, Frobert Y, Pradelles P. Characterization and properties of anti-substance P antiidiotypic antibodies. Methods Enzymol 1989; 178:275-300)] and vasoactive intestinal peptide (VIP; utilizing a monoclonal antibody toward VIP receptors of an adenocarcinoma cell line (Pichon J, Hirn M, Muller J-M, Mangeat P, Marvaldi J. Anticell surface monoclonal antibodies which antagonize the action of VIP in a human adenocarcinoma cell line (HT29). EMBO J 1983;2:1017-22)], respectively. Mucus cells of the submucosal glands (identified by periodic acid Schiff staining) and neuroendocrine cells of the respiratory epithelium (identified by immunoreactivity to protein gene product 9.5) displayed intense VIP receptor-immunoreactivity. Other tissue components known to respond to exogenously administered VIP, e.g., trachealis muscle, lacked VIP receptor-immunoreactivity, indicating that the monoclonal antibody did not label all receptor subtypes. In accordance with the known pharmacological actions of substance P upon the airways, the anti-substance P receptor antibody labeled the trachealis muscle, submucosal glands, and respiratory epithelium, predominantly at the luminal aspect. Since substance P as well as the structurally related tachykinin, neurokinin A, competed with the anti-receptor antibody in binding to the tissue section, it is likely that both NK-1 and NK-2 receptor subtypes were labeled. The present histochemical approach to localize peptide receptors in the trachea allowed precise analysis of distribution unreached by previous studies using autoradiography. Together with pharmacological data, these morphological findings contribute to the understanding of the sequences of events evoked by the neuropeptides, substance P and VIP, in the human trachea.

Antibodies, Monoclonal↗

Results in surgery of pulmonary metastases.

Nowadays surgical treatment of pulmonary metastases is a generally accepted therapeutic concept. Between 1973 and 1991 surgical resection was indicated in 655 patients, and 752 thoracotomies were carried out including 65 laser resections. Median sternotomy has become the preferred access, as the preoperative staging is not exact enough concerning the number of the metastases. This access offers the possibility to examine both lungs during the operation. In 521 operations, wedge resections were carried out, in 199 operations, a lobectomy was necessary. Overall 30-day mortality amounted to 2.8%. The probability to survive 1 year amounted to 71%, to survive 3 years to 42% and to survive 5 years to 31%. Irrespective of the primary tumour, the radicality of the operation is a statistically prognostic factor. Carcinomas showed better prognosis than sarcomas. The isolated examination of the different groups of primary tumors (mammary carcinomas, testicular carcinomas, hypernephromas, melanomas, colorectal carcinomas, osteosarcomas and soft tissue sarcomas) revealed a different influence of various prognostic factors, e.g. the number of metastases and the disease-free interval. Surgery of pulmonary metastases is part of an interdisciplinary concept of oncological therapy, which offers a prolongation of life to most patients and cure to some. If a prolongation of life cannot be achieved, an improvement of life quality can be obtained by surgical treatment.

Adolescent↗

[Extended resection in tumor surgery of the lung].

Out of 3823 prospectively followed patients with bronchial carcinoma, 1404 were operated upon. After radical resection, prognoses for 5-year survival in T3 and T4 tumors was 22% and 10%, respectively. Resection was carried out in 190 T3 tumors and 202 T4 tumors. Indications are based on existing or imminent complications in advanced locoregional tumor growth. Surgery must be decided on as palliative treatment in a high number of cases. This kind of surgical tumor management requires sophisticated techniques.

Carcinoma, Bronchogenic↗