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1.
Science ; 365(6460): 1441-1445, 2019 09 27.
Article in English | MEDLINE | ID: mdl-31604272

ABSTRACT

Surveys have shown that super-Earth and Neptune-mass exoplanets are more frequent than gas giants around low-mass stars, as predicted by the core accretion theory of planet formation. We report the discovery of a giant planet around the very-low-mass star GJ 3512, as determined by optical and near-infrared radial-velocity observations. The planet has a minimum mass of 0.46 Jupiter masses, very high for such a small host star, and an eccentric 204-day orbit. Dynamical models show that the high eccentricity is most likely due to planet-planet interactions. We use simulations to demonstrate that the GJ 3512 planetary system challenges generally accepted formation theories, and that it puts constraints on the planet accretion and migration rates. Disk instabilities may be more efficient in forming planets than previously thought.

2.
Phytomedicine ; 22(1): 158-64, 2015 Jan 15.
Article in English | MEDLINE | ID: mdl-25636885

ABSTRACT

AIMS: To determine if the phytotherapeutic agent, Bryophyllum pinnatum, could serve as an alternative drug for the overactive bladder syndrome, and to characterise the fraction responsible for the inhibition of detrusor contractility. METHODS: Fractions were prepared from the MeOH extract of B. pinnatum and further analysed by HPLC-PDA-MS. Detrusor muscle strips were prepared from porcine bladders and the electrically induced muscle contractility measured by organ bath. The effect of B. pinnatum leaf press juice (2.5-10%), a flavonoid fraction (0.1-1 mg/ml), and a bufadienolide fraction (0.1-40 µg/ml) on detrusor contractility was assessed and compared with controls (polar fraction (0.5-5 mg/ml) and oxybutynin (10(-8)-10(-6) M)). RESULTS: The press juice, at a concentration of 10% led to a reduction of detrusor contractility. Bladder strips treated with the flavonoid fraction showed a significant reduction of the contractility to 21.3 ± 5.2% (1 mg/ml) while the bufadienolide fraction had no inhibitory effect in the investigated concentrations. The polar fraction showed a reduction of the contractility in a pH-dependent fashion. At 10(-6) M concentration oxybutynin reduced the detrusor contractility to 21.9 ± 4.7%. CONCLUSIONS: The flavonoid fraction of Bryophyllum pinnatum reduces the porcine detrusor contractility in a dose- and time-dependent manner. Fractions from B. pinnatum may be a new pharmacological approach for the treatment of OAB.


Subject(s)
Flavonoids/pharmacology , Kalanchoe/chemistry , Muscle Contraction/drug effects , Plant Extracts/pharmacology , Animals , Bufanolides/pharmacology , Female , In Vitro Techniques , Molecular Structure , Muscle, Smooth/drug effects , Phytotherapy , Plant Leaves/chemistry , Swine , Urinary Bladder/drug effects , Urinary Bladder, Overactive/drug therapy
3.
J Clin Oncol ; 17(4): 1185, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10561177

ABSTRACT

PURPOSE: The objective of this prospective study was to assess the feasibility, toxicity, and efficacy of an intensive trimodality approach in stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-four patients with NSCLC and biopsy-proven N2 nodes (IIIA; n = 25) or N3 nodes or T4 lesions (IIIB; n = 29) were administered two initial cycles of ifosfamide, carboplatin, and etoposide; subsequent radiotherapy (45 Gy, twice-daily 1.5 Gy) with concurrent carboplatin and vindesine; and surgery if the patient's disease was resectable or conventional radiotherapy (16 Gy, 2 Gy/d) if the patient's disease was not resectable or incompletely resectable. RESULTS: Thirty-seven patients (69%) responded to preoperative induction. Forty of 54 patients (74%) had disease that was resectable, with 34 (63%) complete resections (R0). A substantial pathologic response (tumor regression [TR] > 90%) was achieved in 27 of 54 patients (50%) and is revealed as an independent predictor for long-term survival after surgery. Five treatment-related deaths (9%) occurred. With a median follow-up period of 44 months, calculated survival rates at 3 years were 35% for patients with stage IIIA disease, 26% for patients with stage IIIB disease, and 56% for patients with R0 disease and TR > 90%. CONCLUSION: This trimodality approach is feasible and results in encouraging 3-year survival rates in prognostically unfavorable patients with stage III NSCLC. Patients experiencing a 90% degree of pathologic TR were most likely to achieve long-term survival.


Subject(s)
Carcinoma, Small Cell/therapy , Lung Neoplasms/therapy , Adult , Aged , Antineoplastic Agents/therapeutic use , Carcinoma, Small Cell/pathology , Chi-Square Distribution , Combined Modality Therapy , Feasibility Studies , Female , Humans , Lung Neoplasms/pathology , Lymphatic Metastasis , Male , Middle Aged , Preoperative Care , Proportional Hazards Models , Prospective Studies , Radiotherapy Dosage , Survival Analysis , Treatment Outcome
4.
Eur Respir J ; 13(2): 424-9, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10065692

ABSTRACT

In a trimodality treatment approach for stage III non-small cell lung cancer the prognostic impact of pretherapeutic p185neu assessment was evaluated. Fifty-four patients were admitted to chemotherapy followed by twice-daily radiation with concomittant low-dose chemotherapy and subsequent surgery. Immunohistochemical assessment of p185neu expression was performed in paraffin-embedded mediastinal lymph node metastases, by mediastinoscopy biopsy prior to therapy. Paraffin-embedded biopsies of mediastinal lymph node metastases were available in 33 cases. Seven out of eight patients with positive p185neu staining developed distant metastases, in contrast to seven out of 25 negative cases. Expression of p185neu in mediastinal lymph node metastases was a significant predictor for progression-free survival (p=0.047) and resulted mainly from significant differences in metastases-free survival (p185neu-positive versus p185neu-negative: median, 11 versus 19 months; 2- and 3-yr rates, 13% and 0% versus 40% and 32%; p=0.04). On the basis of these preliminary results it was concluded that further evaluation of p185neu expression in trials on neoadjuvant and adjuvant therapy is warranted. When the prognostic impact of p185neu in such trials with larger patient numbers is confirmed, this may contribute to the identification of stratification variables for future treatment approaches of non-small cell lung cancer.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Receptor, ErbB-2/analysis , Adult , Aged , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/secondary , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Immunohistochemistry , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local , Prognosis , Survival Rate
5.
J Clin Oncol ; 16(2): 642-50, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9469353

ABSTRACT

PURPOSE: To assess whether granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces the toxicity of chemotherapy and alters delivered dose-intensity. To assess the feasibility of dose-intensification of chemotherapy in small-cell lung cancer (SCLC) and determine whether it has an impact on outcome. MATERIALS AND METHODS: Patients with good- or intermediate-prognosis SCLC entered a prospective multicenter study that involved a 2 x 2 factorial design with randomization to six cycles of chemotherapy with ifosfamide 5 g/m2, carboplatin 300 mg/m2, etoposide 120 mg/m2 intravenously (I.V.) on days 1 and 2 and 240 mg/m2 orally on day 3, and vincristine 0.5 mg/m2 I.V. on day 15 (V-ICE) every 3 weeks (intensified arm) or every 4 weeks (standard arm). A second double-blind randomization to subcutaneous GM-CSF (250 microg/m2/d) or placebo for 14 days between chemotherapy cycles was made. RESULTS: Three hundred patients were entered. Myelosuppression was the main toxicity, with no significant difference in the incidence or grade between treatment groups. The incidence of febrile neutropenia and bacteriologically confirmed sepsis was unaffected by chemotherapy schedule or use of GM-CSF. Twenty-six percent greater dose-intensity was delivered in the intensified arm, with a trend for greater dose-intensity for those who received GM-CSF. Eighty-three percent of patients achieved a response (51% complete response [CR] rate), with no significant difference in response rates between treatment groups. Survival was significantly increased in the intensified compared with the standard arm (P = .0014); median survival rates were 443 versus 351 days and 2-year survival rates were 33% versus 18%, respectively. CONCLUSION: GM-CSF does not reduce the incidence of complications from myelosuppression of aggressive chemotherapy. Dose intensification of V-ICE to a 3-week schedule in SCLC is not associated with increased toxicity, but appears to improve survival significantly. Future studies should aim to deliver chemotherapy in maximal-tolerated dose-intensities.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Small Cell/drug therapy , Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage , Lung Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Carcinoma, Small Cell/mortality , Double-Blind Method , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Humans , Ifosfamide/administration & dosage , Ifosfamide/adverse effects , Lung Neoplasms/mortality , Male , Middle Aged , Prospective Studies , Survival Rate , Vincristine/administration & dosage , Vincristine/adverse effects
6.
Dtsch Med Wochenschr ; 122(33): 993-8, 1997 Aug 15.
Article in German | MEDLINE | ID: mdl-9296933

ABSTRACT

BACKGROUND AND OBJECTIVE: The overall prognosis of patients with stage IIIA non-small-cell lung cancer is unfavourable (median survival time 12 months). Tolerance to and efficacity of a multimodal neoadjuvant treatment was assessed in a prospective study. PATIENTS AND METHODS: 25 patients (median age 59 [37-69] years), with histologically confirmed mediastinal lymph node metastases, underwent chemotherapy. Immediately after two cycles with carboplatin/Ifosfamid (dimethoate)/etoposide they received hyperfractionated accelerated radiotherapy (45 Gy; 2 x 1.5 Gy daily) with simultaneous administration of carboplatin and vindesine. This was followed by tumour resection. RESULTS: After conclusion of the neoadjuvant treatment 19 of 25 patients (76%) had a remission. Of the 20 operated patients complete resection (R0) was possible in 17 (85%) and 14 of the 20 patients with resection (70%) had histologically demonstrated marked tumour regression. Critical toxicity consisted of pneumonitis and bronchial stump problems. Median survival time of all patients was 24.8 months and for patients with R0 resection 35.9 months. CONCLUSION: Neoadjuvant multimodal treatment of stage IIIA non-small-cell lung cancer can achieve prolongation in survival time. The place of radiotherapy or radiotherapy with chemotherapy in such a treatment concept will need to be defined in a randomized study.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Adult , Aged , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/surgery , Chemotherapy, Adjuvant , Dimethoate/administration & dosage , Etoposide/administration & dosage , Female , Humans , Ifosfamide/administration & dosage , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/radiotherapy , Lung Neoplasms/surgery , Male , Middle Aged , Neoplasm Staging , Prospective Studies , Radiotherapy Dosage , Radiotherapy, Adjuvant , Survival Analysis , Treatment Outcome , Vindesine/administration & dosage
7.
Eur J Haematol ; 59(5): 293-8, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9414640

ABSTRACT

GM-CSF may induce pulmonary complications, such as dyspnea with temporary decreases in oxygen saturation described as first dose effect for higher dosages of intravenous rhGM-CSF. This study investigated possible pulmonary disturbances in adult de novo AML patients receiving yeast rhGM-CSF 24 h prior to chemotherapy under phase II/III conditions. Eighteen patients were monitored for 22 treatment episodes. GM-CSF was given s.c. 1 q.d., 2 q.d. or continuously i.v. at 250 micrograms/m2/d 24 h prior to induction chemotherapy (TAD9, n = 18) and consolidation (TAD9, n = 4). Spirometry, bodyplethysmography, single breath-diffusion capacity (DLCO) and arterial blood gas analyses were obtained prior to GM-CSF, and repeated after 24 h. Pulse oxymetric oxygen saturation (saO2) was registered continuously for the first 16 h within day 1 of rhGM-CSF treatment. Patients were aged 21-75 years. The saO2 monitoring did not reveal any first dose effect. PaO2 values decreased from 78.9 mmHg before GM-CSF to 72.8 mmHg after 24 h (p < 0.01, maximum shift 15 mmHg). PaO2 shifts occurred mainly with pre-existing lowered paO2, but otherwise were independent of age, the route of GM-CSF administration, leukocyte levels, or increase of leukocytes with GM-CSF. Increases in AaDO2 reflected the paO2 shifts (p < 0.05). No dyspnea corresponded to these changes. DLCO values did not decrease significantly after 24 h. Summarily, contemporary dosage of yeast rhGM-CSF avoids short-term oxygen desaturations, but leads to clinically benign impairment in oxygen tension, based on ventilation/perfusion mismatches. This should be taken into account for patients starting at subnormal paO2.


Subject(s)
Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use , Leukemia, Myeloid, Acute/blood , Leukemia, Myeloid, Acute/drug therapy , Oxygen/blood , Adult , Aged , Arteries , Female , Humans , Kinetics , Male , Middle Aged , Partial Pressure , Recombinant Proteins
8.
J Immunol Methods ; 194(1): 95-102, 1996 Jul 17.
Article in English | MEDLINE | ID: mdl-8690945

ABSTRACT

A tricolor flow cytometric application is described which permits the determination of total T lymphocytes, T helper lymphocytes and cytotoxic T lymphocytes, natural killer cells and activated T lymphocytes under the same experimental conditions. Even when the lymphocyte count is low, when there is contamination by dust particles or when the cells are damaged the method works with high specificity and reliability. Lymphocytes are identified on the basis of their expression of the pan-leucocyte marker CD45, their side scatter, and plasma membrane integrity, assessed using the fluorescent DNA dye LDS 751. When lymphocyte subsets assessed by flow cytometry were compared with the standard immunoperoxidase method, a strong correlation was found for the CD3+, CD4+ and CD8+ cells. A weak correlation was found for CD25+ cells (r = 0.5). No correlation was seen for CD56+ cells. The high specificity of the procedure suggests that it could be used routinely for the analysis of lymphocytes in bronchoalveolar lavage fluid (BALF), especially when the BALF is contaminated by inorganic particles. Furthermore the application may contribute to the evaluation of lymphocyte subset analysis in the presence of low cell counts.


Subject(s)
Bronchoalveolar Lavage Fluid/cytology , Flow Cytometry , T-Lymphocyte Subsets/immunology , Humans , Immunophenotyping
9.
Dtsch Med Wochenschr ; 121(20): 658-62, 1996 May 17.
Article in German | MEDLINE | ID: mdl-8635401

ABSTRACT

HISTORY AND CLINICAL FINDINGS: A chest radiogram, performed on a 60-year-old man with unproductive cough for 3 months, showed a space-occupying lesion in the right upper lobe, and breath sounds were diminished in this area. He had been a heavy smoker. His general condition and nutritional state were good. INVESTIGATIONS: Computed tomography, skeletal scintigraphy, bronchoscopy with biopsy and mediastinoscopy established the diagnosis of a locally advanced non-small-cell bronchial carcinoma (stage IIIB or T2N3M0). TREATMENT AND COURSE: Combined adjuvant treatment was begun in the hope of improving the median survival time of 8 months predicted for this tumour stage. After two cycles of a combined chemotherapy scheme (ifosfamide, carboplatin, etoposide) he received hyperfractionated-accelerated radiotherapy (total dose 45 Gy; 1.5 Gy twice daily) together with carboplatin and vindesine. This was followed by a right upper lobectomy with lymphadenectomy. Full remission was confirmed in both the resected specimen and the lymph nodes. The patients remains free of tumour 30 months after the diagnosis. CONCLUSION: Neoadjuvant treatment can significantly improve the prognosis of non-small-cell bronchial carcinoma in stage III. Such patients should therefore be treated according to the appropriate study protocol, if possible.


Subject(s)
Bronchial Neoplasms/therapy , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bronchial Neoplasms/diagnosis , Carcinoma, Non-Small-Cell Lung/diagnosis , Chemotherapy, Adjuvant , Combined Modality Therapy , Humans , Male , Middle Aged , Radiotherapy, Adjuvant
11.
J Hosp Infect ; 32(1): 17-28, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8904369

ABSTRACT

Bronchoscopy with bronchoalveolar lavage (BAL), collection of bronchial secretions (BS) and/or high resolution computed tomography (CT) of the lungs was performed in 70 patients with candida and/or aspergillus pneumonia. The sensitivity of bronchoscopy in detecting histologically proven fungal disease was 59%. Characteristic CT signs were found in 11 of 14 patients with candida pneumonia and 16 of 19 patients with aspergillosis. The more frequent use of bronchoscopy and CT scans between 1990 and 1992 compared with 1986-1989 for the differential diagnosis of new pulmonary infiltrates in immunocompromised patients resulted in earlier antifungal treatment (14 vs. nine days; P < 0 center dot 025). In the second treatment period survival was improved from 36 to 50% (not significant). Bronchoscopy and high resolution CT scans are mutually complementary diagnostic tools and should be performed as early as possible in the course of pneumonia in patients at high risk of fungal diseases.


Subject(s)
Aspergillosis/diagnosis , Candidiasis/diagnosis , Cross Infection/diagnosis , Immunocompromised Host , Lung Diseases, Fungal/diagnosis , Pneumonia/diagnosis , Adolescent , Adult , Aged , Bronchoscopy/statistics & numerical data , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Sensitivity and Specificity , Survival Rate , Tomography, X-Ray Computed/statistics & numerical data
12.
Chest ; 108(2): 464-9, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7634885

ABSTRACT

Characterizing lymphocyte subsets in bronchoalveolar lavage fluid (BALF) by flow cytometry (FC) proper gating of the lymphocyte subpopulation being analyzed is crucial. In order to test lymphocyte gate quality for the first time we used a DNA-dye to evaluate plasmamembrane integrity and thus to mark off fluorescent but not DNA-containing particles (eg, debris). A comparative prospective study between this newly developed FC technique and a standard peroxidase anti-peroxidase (PAP) method was performed. Samples of BALF from 50 patients with various pulmonary diseases were examined. After determination of the total cell yield, a differential cell count was performed. Subsequently, the immunophenotype of pan T lymphocyte CD3-, T-helper lymphocyte CD4-, and T-suppressor lymphocyte CD8-positive lymphocyte subsets was assessed with FC as well as with the PAP method. Both methods showed excellent correlation (CD3: r = 0.81; CD4: r = 0.97; CD8: r = 0.96; p < 0.05, respectively). Comparing the mean +/- SEM, FC tends to overestimate CD3+ cells (90.6 +/- 1.0% vs 85.8 +/- 1.3%). For CD4 (45.0 +/- 3.4% vs 44.4 +/- 3.4%) and CD8 (48.1 +/- 3.5% vs 46.7 +/- 3.5%), there was good agreement. In a clinical setting, the reliability of both methods was equivalent, and FC using a DNA-dye to test lymphocyte gate quality offered a rapid and reliable determination of lymphocyte subsets in BAL.


Subject(s)
Bronchoalveolar Lavage Fluid/cytology , Immunophenotyping/methods , Lymphocytes/classification , Bronchoscopy/methods , Confidence Intervals , Flow Cytometry/instrumentation , Flow Cytometry/methods , Flow Cytometry/statistics & numerical data , Humans , Immunoenzyme Techniques/instrumentation , Immunoenzyme Techniques/statistics & numerical data , Immunophenotyping/instrumentation , Immunophenotyping/statistics & numerical data , Linear Models , Lymphocyte Count , Lymphocytes/immunology , Prospective Studies , Statistics, Nonparametric
13.
Strahlenther Onkol ; 171(7): 390-7, 1995 Jul.
Article in German | MEDLINE | ID: mdl-7631260

ABSTRACT

PURPOSE: In the last years new encouraging methods in the therapy of bronchial carcinoma have been elaborated. The early stages of bronchial carcinoma are still a domain of operative treatment. The long-term results of surgical treatment for locally advanced disease are considered to be unfavourable. Multimodal treatment concepts with simultaneous or consecutive application of radio-chemotherapy followed by surgical resection seem to reveal improved possibilities of therapy. PATIENTS AND METHODS: General treatment consists of 2 blocks of neoadjuvant chemotherapy with carboplatin, ifosfamide and etoposide, followed by a third course, consisting of carboplatin and vindesine. Simultaneously with the third course a hyperfractionated, accelerated radiotherapy with a single dose of 1.5 Gy 10 times per week is applied. The total dose is 45 Gy in 3 weeks, given at least to the 80% isodose. After restaging, tumor resection is carried out. Patients without tumor are randomized for prophylactic brain irradiation. RESULTS: From January 1992 up to 1.10.1993 25 patients have been treated in accordance to the study. All tumors were locally advanced (stage IIIa and IIIb). Until 1.10.1993 4 patients died, 2 of them certainly related to the tumor. Thirteen patients have been resected after neoadjuvant treatment. In 11 of these cases a R0-, and in 2 cases a R1 resection has been carried out. Tumor cells have been found only in 5 histologies. The hematotoxic side effects under competing RTX/CTX seemed to be unproblematical (RTOG/grade II). Problems occurred with 4 cases of serious esophagitis (RTOG/grade III to IV) and 2 cases of pneumonitis with 1 case ending lethally. CONCLUSION: Preliminary results of our study show the feasibility of multimodal treatment. A favourable 1-year survival rate after aggressive multimodal therapy and a high resection rate in previously unresectable patients could be demonstrated.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Bronchogenic/therapy , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Adenocarcinoma/radiotherapy , Adenocarcinoma/surgery , Adenocarcinoma/therapy , Brain/radiation effects , Carboplatin/administration & dosage , Carcinoma, Bronchogenic/radiotherapy , Carcinoma, Bronchogenic/surgery , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/therapy , Chemotherapy, Adjuvant , Combined Modality Therapy , Etoposide/administration & dosage , Female , Humans , Ifosfamide/administration & dosage , Lung Neoplasms/radiotherapy , Lung Neoplasms/surgery , Male , Middle Aged , Prognosis , Prospective Studies , Radiotherapy Dosage , Radiotherapy, Adjuvant , Survival Rate , Vindesine/administration & dosage
14.
Gene ; 159(1): 35-42, 1995 Jun 14.
Article in English | MEDLINE | ID: mdl-7607571

ABSTRACT

We have determined the average gene copy numbers (AGCN) of the erbB-1 gene, encoding the epidermal growth factor receptor (EGF-R), the erbB-2 and the erbB-3 genes in breast, ovarian, oral, and lung cancer tissue by using double-differential PCR (ddPCR). The ddPCR method comprises the co-amplification of the single-copy gene HBB, the erbB-1, erbB-2 and erbB-3 oncogenes and the second single-copy reference gene SOD2 under equal reaction conditions. In a retrospective study the AGCN of the erbB genes and the time up to the appearance of metastases were subjected to life-table analysis in 128 women with primary breast cancer. Patients whose breast cancer tissue showed an AGCN for erbB-1 of less than 0.4 and greater then 1.6, as expected from the literature, for erbB-2 of greater than 2.0 and for erbB-3 of less than 1.75 had decreased disease-free survival (DFS). The quotient of erbB-1 and erbB-2 AGCN was the most significant in multivariate Cox analysis followed by nodal status and progesterone receptor status. In extensive studies a similar association between erbB AGCN and metastasis was seen in ovarian cancer and oral cancer, though erbB oncogene aberrations in those entities were not as frequent as in breast cancer. The AGCN of erbB oncogenes may not be of prognostic value in untreated lung cancer patients.


Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Gene Dosage , Genes, erbB/genetics , Polymerase Chain Reaction/methods , Base Sequence , Breast Neoplasms/chemistry , Breast Neoplasms/mortality , Breast Neoplasms/pathology , DNA, Neoplasm/analysis , Disease-Free Survival , Female , Humans , Lung Neoplasms/chemistry , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Molecular Sequence Data , Mouth Neoplasms/chemistry , Mouth Neoplasms/diagnosis , Mouth Neoplasms/genetics , Neoplasm Metastasis , Ovarian Neoplasms/chemistry , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/genetics , Prognosis , Prospective Studies , Retrospective Studies , Sensitivity and Specificity
15.
Dtsch Med Wochenschr ; 120(18): 646-8, 1995 May 05.
Article in German | MEDLINE | ID: mdl-7750432

ABSTRACT

A now 43-year-old man was known since childhood to have mesenteric and subcutaneous lymphadenopathy. Histological examination of liver biopsies and excision of some lymph nodes when an adult showed epithelioid granulomas, in places with Langhans giant cells. Diagnostic splenectomy revealed no pathological findings. His present admission to hospital was for an infection with high fever. On auscultation moist rales were audible over the apex of the left lung. The chest radiography showed pneumonic infiltration. Blood culture grew Pseudomonas aeruginosa. Ultrasound demonstrated hypoechogenic homogeneous and smoothly circumscribed round foci in the liver hilus and around the coeliac trunk. The upper lobe pneumonia healed under antibiotic treatment. As chronic granulomatosis was suspected, the nitroblue tetrazolium and superoxide production tests were performed. They demonstrated that the capacity of the granulocytes to form oxygen radicals was markedly diminished. Chronic granulomatosis is an inherited disorder of granulocyte function linked to the X-chromosome. It must be included in the differential diagnosis of any unclear granulomatous disease even in adults.


Subject(s)
Granuloma/diagnosis , Granulomatous Disease, Chronic/diagnosis , Liver Diseases/diagnosis , Adult , Age Factors , Autopsy , Diagnosis, Differential , Granuloma/diagnostic imaging , Granuloma/pathology , Granulomatous Disease, Chronic/diagnostic imaging , Granulomatous Disease, Chronic/pathology , Humans , Liver/pathology , Liver Diseases/diagnostic imaging , Liver Diseases/pathology , Male , Ultrasonography
16.
Med Klin (Munich) ; 90(3): 131-3, 1995 Mar 01.
Article in German | MEDLINE | ID: mdl-7723713

ABSTRACT

BACKGROUND: Recently, a high incidence of ultrasound-detected hepatic hematomas due to percutaneous liver biopsy has been reported. Until yet, little is known about the incidence of asymptomatic hepatic hematomas following sonographically guided fine-needle biopsy. PATIENTS AND METHODS: For that reason, we carried out a prospective study with sonographic examinations before and after liver biopsy in 160 patients. 51 patients, aged 50 to 83, median 67 years, with focal liver lesions had ultrasound-guided liver biopsy using the 0.95 mm-cut biopsy-needle, in 109 patients (17 to 80, median 49 years) with diffuse liver disease percutaneous liver biopsy with the 1.4 mm-needle of Menghini was performed. RESULT: After fine-needle biopsy none of the 51 patients with focal liver lesions displayed liver hematoma on ultrasonography. In the group of patients who underwent percutaneous Menghini biopsy a liver hematoma, sized up to 12 x 5 cm in diameter, occurred four times (3.7%). CONCLUSION: The results of this study indicate that fine-needle biopsy of the liver is a particularly safe diagnostic procedure, when compared with percutaneous Menghini biopsy.


Subject(s)
Biopsy, Needle/instrumentation , Hematoma/diagnostic imaging , Liver Diseases/diagnostic imaging , Liver/pathology , Ultrasonography/instrumentation , Adolescent , Adult , Aged , Aged, 80 and over , Equipment Design , Female , Humans , Liver/diagnostic imaging , Liver Diseases/pathology , Male , Middle Aged , Prospective Studies
17.
Eur J Haematol ; 54(3): 157-62, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7720835

ABSTRACT

In a prospective study 90 patients with haematologic malignancies (57 acute leukaemias, 6 Hodgkin's Diseases, 15 Non-Hodgkin Lymphomas, 12 other diseases), with fever exceeding 38.4 degrees C and newly developed pulmonary infiltrates underwent bronchoscopy obtaining bronchoalveolar lavage, bronchial washings and protected brush specimen (n = 71). Pneumonias due to gram-negative bacteria (n = 38) and fungi (n = 34) were most frequent. Bronchoscopic specimens yielded 226 isolates (2 different organisms/bronchoscopy on average). 112 organisms were finally regarded as causing pneumonia. Sensitivity of bronchoscopy in diagnosing infectious episodes was 66%, but only 4 out of 13 non-infectious pulmonary infiltrates could be identified. Bronchoscopy was most effective in the diagnosis of pneumocystis carinii and herpes virus pneumonia, whereas sensitivity and specificity of detecting fungal and bacterial pneumonia were low. Empirical antimicrobial therapy was verified by evaluation of bronchoscopic samples in 25 out of 90 cases. Empirical therapy was successfully changed according to the results of invasive samplings in 34 out of 90 cases. Early identification of causative pathogens had a significant impact on survival.


Subject(s)
Bronchoscopy/methods , Leukemia/complications , Lung Diseases/diagnosis , Lymphoma/complications , Opportunistic Infections/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Bronchoalveolar Lavage Fluid , Diagnosis, Differential , Female , Humans , Lung Diseases/microbiology , Male , Middle Aged , Myelodysplastic Syndromes/complications , Pneumonia/diagnosis , Pneumonia/microbiology , Prospective Studies , Sensitivity and Specificity
18.
Ann Hematol ; 70(3): 135-41, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7718642

ABSTRACT

In a retrospective study of 56 patients with hematological malignancies and fungal pneumonia we have analyzed the value of different diagnostic procedures. In all patients (Candida n = 29, Aspergillus n = 23, mixed fungal infection n = 4) bronchoscopy and/or high-resolution computed tomography of the lungs was performed. Cultural detection of fungi in bronchoalveolar lavage was successful in 23/32 Candida and 11/23 Aspergillus pneumonias. Other relevant pathogens were identified by bronchoscopy in 21 cases. Thorax CT scans showed diagnostic evidence of fungal pneumonia in 10/13 Candida and in 16/18 Aspergillus infections. Blood cultures were positive in 9/33 Candida pneumonias and in none of aspergillosis cases. Serological testing and surveillance cultures had only limited value for the early diagnosis of pulmonary mycosis. Our data suggest that bronchoscopy and high resolution CT scans are mutually complementary diagnostic tools with high sensitivity in patients with hematological malignancies and new pulmonary infiltrates. These procedures facilitate the early and reliable recognition of invasive fungal disease which may have a bearing on the initiation, length, and differential therapy of antimycotic drugs.


Subject(s)
Aspergillosis , Candidiasis , Leukemia/complications , Lung Diseases, Fungal/complications , Adolescent , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Antibodies, Fungal/blood , Aspergillosis/diagnostic imaging , Aspergillosis/drug therapy , Aspergillosis/immunology , Bronchoalveolar Lavage Fluid/microbiology , Bronchoalveolar Lavage Fluid/virology , Candidiasis/diagnostic imaging , Candidiasis/drug therapy , Candidiasis/immunology , Female , Humans , Lung Diseases, Fungal/diagnostic imaging , Lung Diseases, Fungal/etiology , Male , Middle Aged , Pneumonia/diagnostic imaging , Pneumonia/drug therapy , Pneumonia/microbiology , Radiography , Time Factors
19.
Lung ; 173(1): 25-33, 1995.
Article in English | MEDLINE | ID: mdl-7776704

ABSTRACT

One hundred immunocompromised HIV negative patients with microbiologically positive pneumonia underwent bronchoalveolar lavage (BAL) studies. Thirty cases showed peripheral neutropenia (< 1000 neutrophils/microL), 70 did not. The total cell number in BAL, the differential cell counts, and the lymphocyte subsets (CD4, CD8, CD19, CD57) were measured. Patients with pneumonia and normal or elevated peripheral neutrophils had a significantly increased total number of cells in BAL compared to patients with peripheral neutropenia (3.2 +/- 2 vs 1.3 +/- 0.6 x 10(5) cells/ml2 lavage fluid, p < 0.01). Ninety percent of the BAL differential cell counts obtained in patients exceeding 1000 neutrophils/microL showed a lymphocytic and/or neutrophilic alveolitis, whereas only 54% of patients with peripheral neutropenia displayed abnormal counts (p < 0.01). Yet the typical pattern of neutrophilic alveolitis was found more often for peripheral neutrophil counts over 1000/microL with high significance (p < 0.0001). Abnormal BAL cell patterns for neutropenic patients uniformly showed a lymphocytic alveolitis, only 10% additionally conformed with the pattern of neutrophilic alveolitis. Patients with pneumonia with and without peripheral neutropenia had similar findings in BAL lymphocyte subsets and exhibited a reduced CD4/CD8 ratio compared to controls (p < 0.05). The high susceptibility of severe neutropenic patients to pulmonary, especially fungal infections may be explained by the local lack of neutrophils.


Subject(s)
Bronchoalveolar Lavage Fluid/immunology , Lung Diseases, Fungal/immunology , Lymphocyte Subsets/immunology , Neutropenia/immunology , Opportunistic Infections/immunology , Pneumonia, Bacterial/immunology , Adolescent , Adult , Aged , Biopsy , Female , HIV Seronegativity/immunology , Humans , Immune Tolerance/immunology , Lung/immunology , Lung/pathology , Lung Diseases, Fungal/pathology , Lymphocyte Count , Male , Middle Aged , Neutrophils/immunology , Pneumonia, Bacterial/pathology
20.
Respiration ; 62(6): 341-7, 1995.
Article in English | MEDLINE | ID: mdl-8552866

ABSTRACT

Bronchoscopy obtaining bronchoalveolar lavage (BAL) fluid and bronchial secretions (BS) and/or high-resolution computed tomography (CT) of the lungs were performed in 33 patients with pulmonary aspergillosis from 1987 to 1992. The sensitivity of BAL fluid or BS for detecting histologically proven fungal disease was 33 and 50%, respectively, whereas positive serologies were only documented in 8% of the cases. CT scans contributed to the early diagnosis of opportunistic fungal pneumonia: characteristic CT signs were found in 16 of 19 episodes. The more frequent use of bronchoscopy and CT scans between 1990 and 1992 compared to 1987-1989 for the differential diagnosis of new pulmonary infiltrates resulted in earlier appropriate treatment. The average introduction of intravenous (i.v.) antifungal therapy after the onset of pneumonia was shifted from 12 to 7 days (p < 0.05). The timely implementation of i.v. antimycotic therapy had a significant impact on survival. Initiation of antifungal treatment later than 10 days after the onset of pneumonia resulted in a mortality of 90%, as opposed to 41% with an earlier start of antimycotics (p < 0.01). The earlier use of appropriate antifungal therapy in the second treatment period improved survival from 33 to 50% (NS). Bronchoscopy and high-resolution CT scans are mutually complementary diagnostic tools and should be performed as early as possible in the course of pneumonia for patients at high risk for aspergillosis.


Subject(s)
Aspergillosis/diagnosis , Lung Diseases, Fungal/diagnosis , Adolescent , Adult , Aged , Antifungal Agents/administration & dosage , Antifungal Agents/therapeutic use , Aspergillosis/diagnostic imaging , Aspergillosis/drug therapy , Aspergillus/isolation & purification , Bronchoalveolar Lavage Fluid/microbiology , Bronchoscopy , Diagnosis, Differential , Female , Humans , Injections, Intravenous , Lung Diseases, Fungal/diagnostic imaging , Lung Diseases, Fungal/drug therapy , Male , Middle Aged , Opportunistic Infections/diagnosis , Opportunistic Infections/diagnostic imaging , Opportunistic Infections/drug therapy , Pneumonia/diagnosis , Pneumonia/diagnostic imaging , Pneumonia/drug therapy , Pneumonia/microbiology , Retrospective Studies , Sensitivity and Specificity , Sputum/microbiology , Survival Rate , Time Factors , Tomography, X-Ray Computed
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