The proline 12 alanine substitution in the PPARgamma2 gene is associated with increased extent of coronary artery disease in men.

OBJECTIVE: To determine whether there is an independent association between the Pro12Ala polymorphism in the peroxisome proliferator-activated-receptor gamma2 (PPARgamma2)-gene and the extent of coronary artery disease in men. RESEARCH DESIGN AND METHODS: We determined the Pro12Ala polymorphism in the PPARgamma2 gene in 240 male patients undergoing elective coronary angiograpy, and quantitated the degree of CAD by evaluating the extent-score which better correlates with known risk factors than other measures of CAD. RESULTS: The presence of the 12Ala allele was significantly associated with higher CAD extent (r=0.27, p<0.01). CAD extent was also correlated with the extent of insulin resistance (HOMA, r=0.22, p<0.01), and age (r=0.16, p<0.05). Multivariate analysis revealed an independent association between the 12Ala allele PPARgamma2 with extent-score (beta=0.32, p<0.01). CONCLUSIONS: The 12Ala allele in PPARgamma2 correlates with a significantly increased CAD extent in men, which suggest that lower activity of the transcription factor PPARgamma2 is associated with more severe CAD.

A phase I study of paclitaxel in combination with etoposide in patients with stage IIIB/IV non-small cell lung cancer (NSCLC).

Paclitaxel is a new antineoplastic agent with activity in lung cancer. This phase I clinical trial was designed to determine the maximum tolerated dose (MTD) of paclitaxel in combination with etoposide in previously untreated patients with non-small cell lung cancer (NSCLC). Doses of paclitaxel were in the range of 150-225 mg/m2 (d1) and of etoposide in the range of 100-120 mg/m2 (d2-4). The drugs were administered by i.v. infusion over 3 h (paclitaxel) and 2 h (etoposide). The patients received four courses at 21-day intervals. Twenty-four patients (six female, 18 male) entered the trial. The characteristics of the patients were as follows: median age 64 (55-73) years; Karnofsky index 80% (70-90%); stage IIIB n = 7, IV n = 17; histology, 14 adenocarcinoma, 10 squamous carcinoma. Hypersensitivity reactions after paclitaxel were not observed. The most relevant toxic effect observed was neutropenia (WHO grade 3-4). Three episodes of febrile neutropenia, two episodes of absolute neutropenia (< 100/microliter for > 3 days), and one case of mucositis (WHO grade > or = 3 for > 7 days) occurred. It can be concluded that the MTD of paclitaxel in combination with etoposide was reached at doses of 200 mg/m2 paclitaxel (d1) and 100 mg/m2 etoposide (d2-4).

[Therapy of nocturnal asthma: salmeterol versus nocturnal administration of retard theophylline--comparison of effectiveness and tolerance]. / Therapie des nächtlichen Asthmas: Salmeterol versus abendliche Einnahme von retardiertem Theophyllin--Vergleich der Wirksamkeit und der Verträglichkeit.

The aim of the present study was to compare the efficacy and the tolerability of salmeterol and theophylline in patients with nocturnal asthma. 16 patients were entered into a randomized, double-blind, crossover trial. Using a double-dummy technique, salmeterol (50 micrograms b.i.d. by MDI) or theophylline (Uniphyllin; 600 mg nocte orally) were given for periods of 7 days with a wash-out period of 7 days between treatment periods. With salmeterol the number of nights with an overnight fall in peak expiratory peak flow rate (PEFR) of at least 20% was reduced by about 20% compared to about 10% with theophyllin (p < 0.05 for the difference between salmeterol and theophylline). With respect to nocturnal symptoms 62.6% of the patients had rare or non symptoms without and 84.7% with salmeterol, compared to 46.5% without and 67.3% with theophylline (p < 0.05). With respect to the improvement of early morning symptoms, the increase of nights with none or rare symptoms was 46.2% with salmeterol compared to 25.8% with theophylline. The overall parameter of efficacy defined as a) the number of nights with an overnight fall in PEFR or less than 20% als well as b) none or rare nocturnal symptoms and c) none or rare early morning symptoms increased from 23.4% at baseline to 75.1% during treatment with salmeterol compared to an increase from 24.5% at baseline with 54.8% during treatment with theophylline (p < 0.05). 12 patients preferred salmeterol over theophylline (p < 0.05). 3 patients had gastrointestinal disturbances during theophylline treatment. It can be concluded that both salmeterol and theophylline are effective in the treatment of nocturnal asthma. With respect to the overall efficacy and the tolerability salmeterol is superior to theophylline.

[Effectiveness and hematotoxicity of paclitaxel monotherapy in patients with advanced non-small cell bronchial carcinoma (NSCLC)]. / Wirksamkeit und Hämatotoxizität einer Paclitaxel-Monotherapie bei Patienten mit fortgeschrittenem nicht-kleinzelligen Bronchialkarzinom (NSCLC).

In initial studies the dose-limiting toxicity of paclitaxel monotherapy was leukopenia. In these studies, paclitaxel was administered over 24 hrs. The aim of the present phase II clinical trial was to investigate the efficacy and the hematological toxicity of a 3 hr paclitaxel infusion in previously untreated patients with NSCLC. Patients received 4 cycles of a chemotherapy consisting of paclitaxel 225 mg/m2 every three weeks. 30 patients (7 female, 23 male) were enrolled in the study. The characteristics of the patients are as follows: age 64 (47-75 yrs); histology: 19 x squamous cell carcinoma, 11 x adenocarcinoma: 4 x IIIB, 26 x IV; performance status 80 (70-90). After prior administration of an anti-allergic medication, hypersensitivity reactions after paclitaxel were not observed. After the first course of paclitaxel chemotherapy, hematological toxicity was as follows: leukopenia WHO-grade 1-2: n = 13; grade 3-4: n = 7; neutropenia grade 1-2: n = 9; grade 3-4: n = 12; anemia grade 1-2: n = 8; no significant thrombocytopenia. In all patients symptoms of peripheral neurotoxicity (WHO grade 1-2) were observed. 19 patients completed the intended four cycles of chemotherapy. The response rates were as follows: partial remission n = 8 (42%), no change n = 11 (58%). Among these patients, the 1-year survival rate was 63%. The efficacy of paclitacel monotherapy in patients with advanced NSCLC appears to be acceptable. The hematotoxicity of paclitaxel after 3h-infusion was markedly less compared to a 24h-regimen.

[Non-small cell lung cancer (NSCLC) stage IIIA/IIIB. A pilot study of neoadjuvant chemotherapy with paclitaxel and carboplatin]. / Nicht-kleinzelliges Bronchialkarzinom IIIA/IIIB: Eine Pilotstudie zur neoadjuvanten Chemotherapie mit Paclitaxel und Carboplatin.

There is evidence that neoadjuvant chemotherapy may improve treatment results in patients with locally advanced NSCLC. The aim of the present study was to increase resectability rates by induction chemotherapy in NSCLC stage IIIA/IIIB with the new cytostatic combination, paclitaxel and carboplatin. Neoadjuvant treatment consisted of 3 cycles (q21) of chemotherapy with paclitaxel (200 mg/m(2)) and carboplatin (AUC 6). Seven patients with IIIA (T3N2, N-stage confirmed by mediastinoscopy) and 16 patients with IIIB (T4N0-2) entered the study. The response to chemotherapy was as follows: IIIA: 3x partial remission (PR), 2x no change (NC), 2x progressive disease (PD); IIIB: 5x PR, 4x NC, 7x PD. Five patients (71%) with IIIA and 8 patients (50%) with IIIB underwent thoracotomy with complete (R0) tumor resection. In all cases, the pT-stage was lower than the pretherapeutic T-stage. The most relevant adverse effect of chemotherapy was leukopenia WHO-grade 1-2. These data suggest that in many patients with T3N2 and in some patients with primarily unresectable T4N0-2 a neoadjuvant chemotherapy with paclitaxel and carboplatin leads to high response rates allowing a high complete resection rate.

[Hyperfractionated irradiation of non-small cell bronchial cancer. Final results of a Phase II study]. / Hyperfraktionierte Bestrahlung beim nichtkleinzelligen Bronchialkarzinom. Schlussresultate einer Phase-II-Studie.

The study was performed for the evaluation of hyperfractionated radiotherapy in the treatment of non-small-cell lung cancer. From radiobiological data we expected that the twice daily irradiation with reduced single dose should result in a better sparing of the slowly proliferating healthy lung tissue without any loss in the tumoricidal effect. 34 patients were treated conventionally with 30 daily fractions of 2.0 Gy over six weeks and another 34 patients twice daily with 1.3 Gy over five weeks to a total dose of 65 Gy. The interval between two fractions lasted at least six hours. Life table (Kaplan-Meier estimate) indicated no contrast between the therapy schedules. The treatment groups did not differ in local response of the primary, progression-free interval and occurrence of distant metastases, the hyperfractionated schedule was very well tolerated. Comparison of the posttreatment quality of life showed a better course after the hyperfractionated regimen, without reaching a level of significance.

[Thoracoscopic treatment of spontaneous pneumothorax using fibrin pleurodesis]. / Thorakoskopische Behandlung des Spontanpneumothorax mittels Fibrinpleurodese.

In 33 patients with a recurrent spontaneous pneumothorax, a thoracoscopic pleurodesis with fibrin glue was performed under local anesthesia. During an average postoperative observation period of 4 years the relapse frequency was 39% (13 cases). In these cases thoracotomy was performed and a new relapse of pneumothorax occurred in 3 patients (23%): Application of thoracoscopy with fibrin glue pleurodesis should only be applied in those patients without large emphysema vesicles and without large coalescences. Under these conditions the relapse frequency could be reduced to 26%. The thoracoscopic treatment of recurrent pneumothorax by using fibrin glue and local anesthesia in well selected patients is an alternative procedure to thoracotomy.

[Long-term results with the CARE classification for assessing operability before thoracic surgery]. / Langzeitergebnisse für das CARE-Schema zur Beurteilung der Operabilität vor thoraxchirurgischen Eingriffen.

The classification and quantification of the individual risk in accordance with the CARE scheme is suitable not only for enabling appropriate selective peri-operative and post-operative function-supporting therapy, but also for reducing long-term morbidity. The prognosis of both operated and non-operated tumour patients, is determined exclusively by the recurrence and progression of the tumour disease.

[Hyperfractionated irradiation of bronchial cancer. Results of a pilot study]. / Hyperfraktionierte Bestrahlung beim Bronchialkarzinom. Ergebnisse einer Pilotstudie.

The results achieved during recent years in experimental radiotherapy of malignant tumors show more and more the benefit provided by the small individual doses applied in fractionated irradiation. The effects and side effects of a hyperfractionated therapy of the bronchial carcinoma were investigated in a not randomized comparative study. The data of 100 patients were available for evaluation; they showed a tendency to local superiority of hyperfractionated irradiation. The value of hyperfractionation shall be examined in detail in a randomized prospective study.

Lymphocytic plasmocytoid lymphoma with a three-banded gammopathy: reactivity of one of these paraproteins with cytomegalovirus.

We report the case of a 70-year-old woman suffering from small lymphocytic, plasmocytoid lymphoma with abdominal lymphomas and infiltration of the lung and the bone marrow. A three-banded, IgG lambda, IgM lambda and IgA lambda-paraproteinemia was determined using immunofixation. Because of the patient's high antibody titre against cytomegalovirus (CMV), the possible reactivity of these paraproteins with CMV was studied. The immunoglobulins were transferred to nitrocellulose sheets by a contact diffusion blotting system. CMV was applied to these sheets and the IgG lambda-paraprotein was shown to bind CMV. The reactivity of only one of the paraproteins with CMV suggests an oligoclonal origin of this gammopathy. In addition to the malignant disease an abnormal immune response to a CMV infection could be the cause of this three-banded gammopathy.

Palliative therapy of tumor-induced pleural effusions with 90Yttrium-silicate.

In 20 patients with rapidly recurring malignant pleural effusion, 90Yttrium-silicate was intrapleurally instilled after the puncture. In all patients this treatment resulted in marked reduction, or even interruption, of exudate formation. Eleven patients died with an average survival of 166 days. Nine patients are still alive and have been followed up for a mean of 140 days without the pleural effusion recurring. Side effects were not observed, either subjectively or in relation to hematological and other laboratory findings.

Drug-resistant bronchial asthma successfully treated with plasma exchange.

Two patients suffering from allergic bronchial asthma who showed no improvement despite six and four weeks, respectively, of drug therapy were successfully treated with therapeutic plasma exchange. The first patient had no attacks over a period of five months, and the other patient had none for over one year. Although this report only deals with single observations, we believe that therapeutic plasma exchange is of particular value for patients with severe allergic bronchial asthma because it eliminates in addition to immunocomplexes other substances, including antigens, rapidly from the blood. This means that it is possible to directly intervene in the pathomechanism. However, further investigations are necessary in order to corroborate this successful therapy.