Effects of cortisol on memory in women with borderline personality disorder: role of co-morbid post-traumatic stress disorder and major depression.

BACKGROUND: Stress and cortisol administration are known to have impairing effects on memory retrieval in healthy humans. These effects are reported to be altered in patients with major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) but they have not yet been investigated in borderline personality disorder (BPD). METHOD: In a placebo-controlled cross-over study, 71 women with BPD and 40 healthy controls received either placebo or 10 mg of hydrocortisone orally before undertaking a declarative memory retrieval task (word list learning) and an autobiographical memory test (AMT). A working memory test was also applied. RESULTS: Overall, opposing effects of cortisol on memory were observed when comparing patients with controls. In controls, cortisol had impairing effects on memory retrieval whereas in BPD patients cortisol had enhancing effects on memory retrieval of words, autobiographical memory and working memory. These effects were most pronounced for specificity of autobiographical memory retrieval. Patients with BPD alone and those with co-morbid PTSD showed this effect. We also found that co-morbid MDD influenced the cortisol effects: in this subgroup (BPD + MDD) the effects of cortisol on memory were absent. CONCLUSIONS: The present results demonstrate beneficial effects of acute cortisol elevations on hippocampal-mediated memory processes in BPD. The absence of these effects in patients with co-morbid MDD suggests that these patients differ from other BPD patients in terms of their sensitivity to glucocorticoids (GCs).

Gemcitabine and cisplatin as induction regimen for patients with biopsy-proven stage IIIA N2 non-small-cell lung cancer: a phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group (EORTC 08955).

PURPOSE: Our objective was to better define the activity/feasibility of gemcitabine/cisplatin (GC) as induction chemotherapy in patients with stage IIIA N2 non-small-cell lung cancer (NSCLC) followed by surgery or radiotherapy within a large, ongoing comparative study (EORTC 08941). PATIENTS AND METHODS: Forty-seven chemotherapy-naive patients with NSCLC, median age of 58 years, stage IIIA N2 disease, World Health Organization performance status of 0 or 1, and the ability to tolerate a pneumonectomy received gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 and cisplatin 100 mg/m(2) on day 2, every 4 weeks. Patients received induction chemotherapy (three cycles) before re-evaluation and randomization to surgery or radiotherapy. RESULTS: Grade 3/4 thrombocytopenia, the main hematologic toxicity, occurred in 60% of patients but was not associated with bleeding. Full-dose gemcitabine was given in 48% of the courses. Severe nonhematologic toxicity was uncommon. Two patients with preexisting, autoimmune pulmonary fibrosis had deterioration of pulmonary function after radiotherapy. Thirty-three (70.2%; 95% confidence interval, 55.1% to 82.7%) of the 47 eligible patients had objective responses (three complete responses and 30 partial responses). Mediastinal nodes were tumor-free after induction therapy in 53% of cases. Resections were considered complete in 71% of the patients who underwent thoracotomy after induction therapy. Median survival for all recruited patients (N = 53) was 18.9 months, with an estimated 1-year survival rate of 69%. CONCLUSION: In patients with N2 stage IIIA NSCLC, GC is a highly active and well-tolerated induction regimen. GC should be explored in combination with surgery or radiotherapy in stage I and II patients.

A short (3-day) course of azithromycin tablets versus a 10-day course of amoxycillin-clavulanic acid (co-amoxiclav) in the treatment of adults with lower respiratory tract infections and effects on long-term outcome.

The efficacy and safety of a 3-day regimen of azithromycin prescribed in the new tablet form and of a 10-day regimen of amoxycillin clavulanic acid (co-amoxiclav, Augmentin) were compared in patients with acute lower respiratory tract infections. Of the 144 enrolled patients, 123 had a Type 1 acute exacerbation of chronic bronchitis (AECB), three patients had pneumonia, and 18 had purulent bronchitis. Treatment was successful, defined as cure or major improvement on day 14, in 59/62 (95%) patients in the azithromycin treatment group compared with 54/61 (90%) patients in the co-amoxiclav. At 30 days, the incidence of success was 77% (48/62) in the azithromycin treated group, compared with 66% (40/61) of co-amoxiclav-treated patients. At 60 days, incidences were 66% (41/62) and 59% (36/61), respectively. Several pathogens were isolated: Haemophilus influenzae in 21 patients (minimum inhibitory concentration (MIC) range for azithromycin 0.12-4 mg/l; co-amoxiclav 0.25-4 mg/l); Streptococcus pneumoniae in nine (MIC azithromycin < or = 0.06 > or = 256 mg/l; co-amoxiclav < or = 0.06-1 mg/l); and Moraxella catarrhalis in 11 (MIC azithromycin < or =0.06-2 mg/l; co-amoxiclav < or = 0.06-0.5 mg/l). Microbiological response rates were comparable. A significant correlation between clinical and microbiological cure was found (p = 0.02, power 0.6). In 15 (10%) patients, positive serology for viruses or atypical pathogens was found. In the co-amoxiclav-treatment group, 24 patients had mild adverse events (12 diarrhoea), compared with 27 treated with azithromycin (p = 0.47). It is concluded that a 3-day regimen of azithromycin prescribed as tablets is as clinically and microbiologically effective as a 10-day regimen of co-amoxiclav in the treatment of acute lower respiratory tract infections. Moreover, since the percentage of viral infections was low and a significant correlation between microbiological and clinical cure was found, this study shows that clinical symptoms can be used to establish which patients with AECB (Type 1) should be treated with antimicrobial agents.

Salmeterol/fluticasone propionate (50/500 microg) in combination in a Diskus inhaler (Seretide) is effective and safe in the treatment of steroid-dependent asthma.

This multicentre double-blind, double-dummy study compared the safety and efficacy of a new combination Diskus inhaler containing both salmeterol 50 microg and fluticasone propionate 500 microg (Seretide, GlaxoWellcome, France) with the same doses of the two drugs delivered via separate Diskus inhalers and with the same dose of fluticasone propionate alone. Patients were eligible for study entry if they had received an inhaled corticosteroid continuously for 12 weeks prior to run-in, and had received treatment with beclomethasone dipropionate or budesonide 1500-2000 microg day(-1) or fluticasone propionate 750-1000 microg day(-1) for at least 4 weeks prior to run-in. In total, 503 patients receiving inhaled corticosteroids were randomized to 28 weeks' treatment with either salmeterol/fluticasone propionate (50/500 microg) via a single Diskus inhaler (combination) and placebo, or salmeterol 50 microg and fluticasone propionate 500 microg administered via separate Diskus inhalers (concurrent), or fluticasone propionate 500 microg and placebo. All treatments were administered twice daily, mean morning peak expiratory flow rate (PEFR) and asthma symptoms were measured for the first 12 weeks and safety data were collected throughout the 28-week study. Over weeks 1 to 12, improvement in adjusted mean morning PEFR was 35 and 33 l min(-1), respectively, in the combination and concurrent therapy treatment groups (12 and 10% increase from baseline, respectively). The mean difference between treatments was -3 l min(-1) (90% confidence interval -10.4 l min(-1)) which was within the criteria for clinical equivalence. However, the combination therapy was statistically significantly superior to fluticasone propionate alone for mean morning PEFR (P<0.001) and other measures of lung function, whilst clinical equivalence of the combination and concurrent therapies was observed. All three treatments were well tolerated. In addition, there were no differences between the three treatments in either the c.hange in serum cortisol or urinary cortisol concentrations, which, for each treatment group, were no significantly different from baseline at the end of the treatment period. Thus, the combination of salmeterol and fluticasone propionate in a single inhaler is as well tolerated and effective in achieving asthma control in steroid-dependent patients as the separate administration of the two drugs, and both combination and concurrent therapy are superior to administration of the same dose of corticosteroid alone.

Prophylactic cranial irradiation in limited disease small-cell lung cancer in complete remission: a retrospective analysis.

Recently a meta-analysis showed an improved survival probability of prophylactic cranial irradiation (PCI) in limited disease small-cell lung cancer (LD SCLC) in complete remission after chemotherapy. We evaluated treatment results of PCI+ and PCI- in these patients. Whether PCI (n = 65) or no PCI (n = 37) was administered did not depend either on patients or on tumour characteristics. After 2 years the incidence of brain metastases was 11% in PCI+ patients and 51% in PCI- patients. Both disease-free survival and overall survival were significantly longer after PCI. PCI reduces the incidence of brain metastases, prolongs brain metastases-free period, and overall survival in LD SCLC patients in complete remission after chemotherapy.

Staging of lymph nodes with FDG dual-headed PET in patients with non-small-cell lung cancer.

Accurate assessment of mediastinal lymph node involvement in patients with non-small-cell lung cancer (NSCLC) is necessary to select patients for direct surgical treatment. The aims of the present study were to assess the feasibility of staging NSCLC with FDG using a dual-headed positron emission tomographic (PET) camera and to compare this non-invasive technique with computed tomography (CT) and lymph node sampling, since both modalities are currently used for staging NSCLC. Thirty-three patients (29 men and 4 women, mean age 60 years) with newly diagnosed NSCLC were studied. In all patients, CT, FDG dual-headed PET and mediastinoscopy were performed within 4 weeks. The results of mediastinoscopy were used to select patients for thoracotomy. For both the assessment of individual lymph node involvement and the patient-based classification, the results of FDG dual-headed PET and CT were compared using the McNemar test. Thirty-one of 187 lymph nodes studied contained tumour metastases. FDG dual-headed PET showed a significantly higher sensitivity (P < 0.001) and specificity (P < 0.001) than CT. FDG dual-headed PET and CT correctly staged 27 and 20 patients, respectively. Due to the significantly higher negative predictive value of FDG dual-headed PET versus CT (P = 0.012), it was a better non-invasive diagnostic tool for selecting patients for surgery. In seven of eight patients, additional intrapulmonary sites of increased uptake were found, which revealed malignancy on histological examination. CT was false-negative in three of these patients. In one patients, increased FDG uptake was caused by an infection. In conclusion, it is possible to stage mediastinal lymph nodes in patients with NSCLC using a dual-headed PET camera. The high negative predictive value of FDG dual-headed PET suggests that mediastinoscopy may be omitted in patients with NSCLC.

Balancing of nitrogen conversion in deammonifying biofilms through batch tests and GC/MS.

Growth carriers from a technical deammonifying moving-bed WWTP were used in batch tests to determine possible N-conversion reactions under varying oxygen and substrate conditions. Deammonification, denitrification, and nitrification reactions could be proved using conventional analysis, combined with gas chromatography/mass spectrometry analysis to get additional information about 15N-isotope labelled gaseous end products of the different reactions. In this orientating study N2O could be observed in some cases up to 12% of the total gas production. N2O production came from incomplete denitrification processes under anoxic or oxygen-limiting conditions and in the absence of organic substrate, as if structural components of deammonifying biofilms play a crucial role for the portion of side-reactions, leading to undesirable gaseous end products.

[Muscle weakness as initial symptom of bronchial carcinoma]. / Spierzwakte als eerste uiting van bronchuscarcinoom.

Lambert-Eaton myasthenic syndrome was diagnosed in three patients, two men aged 55 and 57 and one woman aged 66 years. After a variable time interval a small cell carcinoma of the lung was detected in all three patients. Two already had metastases outside the thorax and died, the other patient was doing well after treatment with chemotherapy and radiotherapy. The short survival of patients with a small cell carcinoma requires early diagnosis, and paraneoplastic phenomena such as the Lambert-Eaton myasthenic syndrome can be the earliest presenting sign. The syndrome can be diagnosed by electromyography.

Occupational asbestos exposure: how to deal with suspected mesothelioma cases--the Dutch approach.

INTRODUCTION: Patients with asbestos-related diseases, such as malignant mesothelioma (MM), are not uniformly treated in Europe when they apply for compensation. In The Netherlands, the Institute of Asbestos Victims (IAV) acts on behalf of patients with a malignant mesothelioma. In the majority of cases, the diagnosis is clear but in some, uncertainty remains. In these cases a specialist opinion of the Mesothelioma Group of the Dutch Thoracic Society (DTS) is required. The process of data handling and final outcome for these patients is discussed and compared with the situation in other European countries. MATERIALS AND METHODS: Dutch patients with a possible malignant mesothelioma and occupational exposure to asbestos presented their cases to the IAV. In 10% of the cases, pathological confirmation of a malignant mesothelioma could not be obtained. These cases were presented to the Mesothelioma Group to obtain a clinical diagnosis based on clinical reports, occupational history, X-ray examination and other factors. Each case was reviewed by three independent pulmonologists experienced in MM. The majority view was binding for acceptance or rejection of the diagnosis. RESULTS: In the period January 2000 until May 2005, the IAV received 1747 cases for compensation. In 161 cases no definitive diagnosis could be made on pathology and were presented to the Mesothelioma Group. Of these cases, 117 (73%) were considered to be compatible with the clinical diagnosis malignant pleural mesothelioma. Forty-four cases (27%) were rejected. In 75% of the cases (112 of 150), the conclusion of the three independent specialists was unanimous; in 11 cases one specialist refrained from a diagnosis. The median time from request to submission of the report was 34 days (range 1-185 days). CONCLUSIONS: Compared with other European countries, this approach, as determined by the IAV and Mesothelioma Group of the DTS, is an effective and rapid way to investigate claims of patients with a possible occupationally related malignant mesothelioma.

Collisional blockade in microscopic optical dipole traps.

We analyze the operating regimes of a very small optical dipole trap, loaded from a magneto-optical trap, as a function of the atom loading rate, i.e., the number of atoms per second entering the dipole trap. We show that, when the dipole trap volume is small enough, a "collisional blockade" mechanism locks the average number of trapped atoms on the value 0.5 over a large range of loading rates. We also discuss the "weak loading" and "strong loading" regimes outside the blockade range, and we demonstrate experimentally the existence of these three regimes.

Sub-poissonian loading of single atoms in a microscopic dipole trap.

The ability to manipulate individual atoms, ions or photons allows controlled engineering of the quantum state of small sets of trapped particles; this is necessary to encode and process information at the quantum level. Recent achievements in this direction have used either trapped ions or trapped photons in cavity quantum-electrodynamical systems. A third possibility that has been studied theoretically is to use trapped neutral atoms. Such schemes would benefit greatly from the ability to trap and address individual atoms with high spatial resolution. Here we demonstrate a method for loading and detecting individual atoms in an optical dipole trap of submicrometre size. Because of the extremely small trapping volume, only one atom can be loaded at a time, so that the statistics of the number of atoms in the trap, N, are strongly sub-poissonian (DeltaN2 approximately 0.5N). We present a simple model for describing the observed behaviour, and we discuss the possibilities for trapping and addressing several atoms in separate traps, for applications in quantum information processing.

Treatment of asthma by the inhaled corticosteroid ciclesonide given either in the morning or evening.

The study addressed the question whether the novel inhaled prodrug corticosteroid ciclesonide is equally effective when inhaled in the morning compared to the evening. For this purpose a double-blind, randomized, parallel group study was initiated in which 209 asthmatic patients (forced expiratory volume in one second = 50-90% predicted) inhaled either 200 microg ciclesonide in the morning or in the evening, for 8 weeks. Efficacy was assessed by means of spirometry as well as daily recordings of morning and evening peak expiratory flow (PEF), symptoms and use of rescue medication. The 24-h urinary cortisol excretion was measured to evaluate any effect on hypothalamic-pituitary-adrenol axis. Ciclesonide significantly improved asthma control. Morning and evening administration was shown to be equally effective for the different spirometry variables, evening PEF, symptoms, use of rescue medication and number of asthma exacerbations. Regarding morning PEF, the improvements after evening dosing were more prominent and equivalence of morning and evening administration could not be demonstrated. No relevant influence on cortisol excretion was found. Overall, the study indicates that ciclesonide can be given either in the morning or in the evening to meet the patients' preference and individual medical needs, although evening administration may lead to a more pronounced improvement in morning peak expiratory flow.

Superior vena cava obstruction caused by radiation induced venous fibrosis.

Superior vena cava syndrome is most often caused by lung carcinoma. Two cases are described in whom venous obstruction in the superior mediastinum was caused by local vascular fibrosis due to radiotherapy five and seven years earlier. The development of radiation injury to greater vessels is discussed, together with the possibilities for treatment of superior vena cava syndrome.

Single-agent gemcitabine in patients with resistant small-cell lung cancer.

OBJECTIVE: This study was conducted to assess the activity and toxicity ofgemcitabine in patients with resistant small-cell lung cancer (SCLC). PATIENTS TAND METHODS: Forty-one patients with limited- or extensive-stage SCLC, who were previously treated with at least one chemotherapeutic regimen and progressed during or within three months of finishing the last regimen, were treated with 1000 mg/m2 gemcitabine on days 1, 8, and 15 of a four-week cycle. RESULTS: Thirty-eight patients were evaluable for response. Five partial and no complete responses were seen, for an overall response rate of 13% (95% confidence interval (CI): 6%-27%). Time to progression varied from 4 to 20 weeks, with a median of 8 weeks. Median survival was 17 weeks (range 4-84 weeks). Hematological toxicity mainly consisted of NCI-CTC grade 3 thrombocytopenia (29% of patients) and, to a lesser extent, grade 3 leukopenia (18% of patients). Non-hematological toxicity was mild, with nausea being the most commonly reported event. CONCLUSIONS: Gemcitabine has modest activity in patients with resistant SCLC. There is some non-cross resistance to most agents against SCLC.