Availability of diagnostic facilities in the Netherlands for patients with suspected pulmonary embolism. ANTELOPE Study Group. Advances in New Technologies Evaluating the Localisation of Pulmonary Embolism

Pulmonary embolism remains a complex diagnostic problem. Although accurate and cost-effective, the 'Dutch consensus' strategy is not widely applied. We assessed the availability and investment plans of the different facilities used in this strategy. Furthermore, the current and future availability of new diagnostic modalities was investigated. A questionnaire was sent to all Dutch hospitals. The questionnaire contained separate sections with questions for the hospital management and the medical practitioners at the departments of radiology, nuclear medicine, internal medicine and pulmonology. Five hundred and eighty-four questionnaires were sent out (response rate 68%). Forty-three percent of the hospitals had no nuclear medicine facility, 11% had no pulmonary angiography facility, and 59% had no spiral CT scan (SCTA). Forty-six percent of the responding hospitals had a nuclear medicine facility; and 5% used Technegas for ventilation studies. Strategies with SCTA were available in about 27% of the hospitals. Due to future investments this number will increase to approximately 55%. Strategies with Technegas were available in 2.4% of the hospitals, this number might increase to 25% if Technegas is proven accurate. The 'Dutch consensus' strategy is available in two-thirds of the hospitals. All other strategies were less feasible. Several equivalent strategies for diagnosing pulmonary embolism should be developed. These strategies should be accurate, widely available and accepted.     

Expression of the human major vault protein LRP in human lung cancer samples and normal lung tissues

BACKGROUND:: The recently discovered LRP protein has been shown to be involvedin drug resistance and possibly in detoxification processes. MATERIALS AND METHODS:: To study the relation between LRP expression and exposure tocigarette smoke, LRP immunoreactivity was evaluated in 39 paraffinembedded normal lung tissues derived from patients operatedon for pneumothorax, and related to amount of pack years smoked.We also studied the LRP protein expression in 36 non-small-celllung cancer (NSCLC) samples and related the expression patientcharacteristics and survival. Furthermore 17 lung tumor samples(10 NSCLC and 7 SCLC) derived from patients treated with chemotherapywere analysed in order to investigate the relation between LRPor MRP expression and patient's response to chemotherapy. RESULTS:: In the normal lung tissues, LRP intensity levels were not correlatedto the amount of pack years smoked, although a trend was seenfor higher LRP intensity levels in patients who smoked morethan 10 pack years. LRP expression was significantly higherin NSCLC samples than in SCLC samples, and all SCLC samplesdisplayed very low LRP expression. Within NSCLC, squamous celland adenocarcinomas had higher LRP expression than large cellundifferentiated and mixed tumors. In NSCLC patients LRP expressionwas not a prognostic factor for survival. At initial analysisLRP expression levels did not predict for the response to chemotherapy.Only 3 out of 17 patients expressed MRP, and all SCLC sampleswere MRP negative. CONCLUSION:: Striking different expression levels were seen between NSCLCand SCLC for both LRP and MRP. In a preliminary analysis LRPexpression was not predictive for response to chemotherapy inlung cancer patients. In pneumothorax patients LRP levels werenot correlated with the amount of pack years smoked. detoxification, immunohistochemistry, LRP, lung cancer, MRP, multidrug resistance     

Assessing a system to capture stray aerosol during inhalation of nebulized liposomal cisplatin.

The aim of this study was to determine the efficacy of using a high-efficiency particulate air (HEPA) filter air cleaning system, a demistifier, to reduce the potential risk of fugitive aerosol contact in health care personnel working with patients inhaling nebulized liposomal encapsulated SLIT (Sustained-release Lipid Inhalation Targeting) Cisplatin. Filters were used to sample platinum in the air outside the tent and from the tent's exhaust stream. Air collection was performed under three conditions: (1) during patient dosing (14 h of air collection); (2) immediately after the patient has left the demistifier tent (4 h of air collection); and (3) when 7 mL of drug product was nebulized to dryness in the tent without a patient being present. Filters were collected, and placed in an extraction solvent. Subsequently, the solvent was assayed for platinum content by inductively coupled plasma-mass spectrometry (ICP-MS). Platinum levels in the extraction solvent were indistinguishable from the blank controls for all conditions. Measured levels were below workplace exposure limits established for cisplatin by the Occupational Safety and Health Administration (i.e., 2 ng . (L(1)). In addition, the demistifier was able to effectively capture aerosolized SLIT Cisplatin following nebulization of 7 mL of drug product to dryness in the tent. The demistifier tent is effective at containing any nebulized liposomal encapsulated cisplatin during patient treatment. Importantly, because the tent's HEPA filtration system is effective at removing any nebulized liposomal cisplatin, the exhausted air, which is free of platinum, can be returned into the room with no additional ventilation precautions.     

Prediction of peak oxygen uptake in men using pulmonary and hemodynamic variables during exercise

PURPOSE: Many attempts have been made to predict peak VO2 from data obtained at rest or submaximal exercise. Predictive submaximal tests using the heart rate (HR) response have limited accuracy. Some tests incorporate submaximal gas exchange data, but a predictive test without gas exchange measurements would be of benefit. Addition of stroke volume and pulmonary function (PF) measurements might increase the predictability of a submaximal exercise test. METHODS: In this study, an incremental exercise test (10 W x min(-1)) was performed in 30 healthy men of various habitual activity levels. Step-wise multiple regression analysis was used to isolate the most important predictor variables of peak VO2 from a set of measurements of PF: lung volumes, diffusion capacity, airway resistance, and maximum inspiratory and expiratory pressures; gas exchange; minute ventilation (V(E)), tidal volume (V(T)), respiratory exchange ratio (RER = carbon dioxide output divided by VO2); and hemodynamics (HR, stroke index (SI) = stroke volume/body surface area, and mean arterial pressure). These measurements were made at rest and during submaximal exercise. RESULTS: Using the set of PF variables (expressed as percentages of predicted), FEV1 explained 30% of the variance of peak VO2. No other PF variables were predictive. After addition of resting hemodynamic data, SI was included in the prediction equation, raising the predictability to 40%. At the 60-W exercise level, 48% of the variance in peak VO2 could be explained by SI and FEV1. At 150 W, the prediction increased to 81%. At this level VCO2/O2 (RER) also entered the prediction equation of peak VO2: 6.44 x FEV1(%) + 13.0 x SI - 1921 x RER + 2380 (SE = 142 mL x min(-1) x m(-2), P < 0.0001). Leaving out the gas exchange variable RER, maximally 64% of the variance in peak VO2 could be explained. CONCLUSION: In conclusion, inclusion of pulmonary function and hemodynamic measurements could improve the prediction accuracy of a submaximal exercise test. The submaximal exercise test should be performed until a level of 150 W is reached. Noninvasive stroke volume measurements by means of EIC have additional value to measurement of HR alone. Finally, measurement of gas exchange significantly improves the predictability of peak VO2.     

Standard versus intensified chemotherapy with granulocyte colony-stimulating factor support in small-cell lung cancer: a prospective European Organization for Research and Treatment of Cancer-Lung Cancer Group Phase III Trial-08923.

PURPOSE: To assess the impact on survival of increasing dose-intensity (DI) of cyclophosphamide, doxorubicin, and etoposide (CDE) in small-cell lung cancer (SCLC). PATIENTS AND METHODS: Previously untreated SCLC patients were randomized to standard CDE (cyclophosphamide 1,000 mg/m(2) and doxorubicin 45 mg/m(2) on day 1, and etoposide 100 mg/m(2) on days 1 to 3 every 3 weeks, for five cycles) or intensified CDE (cyclophosphamide 1,250 mg/m(2) and doxorubicin 55 mg/m(2) on day 1, and etoposide 125 mg/m(2) on days 1 to 3 with granulocyte colony-stimulating factor [G-CSF] 5 micro g/kg/d on days 4 to 13 every 2 weeks, for four cycles). Projected cumulative dose was almost identical on the two arms, whereas projected DI was nearly 90% higher on the intensified arm. Two hundred forty-four patients were enrolled. The first 163 patients were also randomized (2 x 2 factorial design) to prophylactic antibiotics or placebo to assess their impact on preventing febrile leukopenia (FL). This report focuses on chemotherapy DI results. RESULTS: With a median follow-up of 54 months, 216 deaths have occurred. Actually delivered DI on the intensified arm was 70% higher than on the standard arm. Intensified CDE was associated with more grade 4 leukopenia (79% v 50%), grade 4 thrombocytopenia (44% v 11%), anorexia, nausea, and mucositis. FL and number of toxic deaths were similar on the two arms. The objective response rate was 79% for the standard arm and 84% for the intensified arm (P =.315). Median survival was 54 weeks and 52 weeks, and the 2-year survival rates were 15% and 18%, respectively (P =.885). CONCLUSION: A 70% increase of CDE actual DI does not translate into an improved outcome in SCLC patients.     

Long term survival of small cell lung cancer patients after chemotherapy.

Eighty-one patients with small cell lung cancer (SCLC) with a survival of more than 2 years after start of chemotherapy were studied. Twenty-six of the 28 patients who died of relapsed SCLC had in fact relapsed before two years and of the 55 who had not then only two (4%) relapsed subsequently. It is stressed that with such observations treatment related factors should be taken in account. Second tumours were observed in ten patients, nine proven malignant. Of the eight patients with non-small cell lung cancer three had residual disease after initial chemotherapy. In our patient group after a 2 year disease-free interval the risk of developing non-small cell lung cancer seems higher than a subsequent relapse of SCLC.     

Model of normal prepubertal growth

Overheating may cause terminal apnoea and cot death. Rectal temperature and breathing patterns were examined in normal infants at home during the first 6 months of life. Twenty one infants had continuous overnight rectal temperature and breathing recordings for 429 nights (mean 20.4 nights, range 7-30) spaced over the first six months of life. Periods when breathing was 'regular' were directly marked on single night records. Sleep state was determined from respiratory variables. 'Regular' breathing was a reliable marker of 'quiet' sleep (specificity 93%). The duration of 'quiet' sleep increased from 6 to 22 minutes from two weeks to three months of age and then remained static, as did the proportion of sleep spent in the quiet phase (9% to 34%). Rectal temperature fell during 66% of quiet sleep and usually rose during rapid eye movement (REM) sleep. The drop in rectal temperature was maximal at the start of quiet sleep, whereas the maximum rise during REM sleep was reached after 10 to 15 minutes. Oscillations in rectal temperature are associated with changes in sleep and breathing state. The maturation of rectal temperature patterns during the first six months of life are closely related to a maturation of sleep state and breathing patterns.     

Comparison of IgG subclasses in foetal serum, maternal serum at delivery and milk in IgA-deficient and control women

Immunoglobulin G subclass concentrations were measured in paired foetal (cord) and maternal serum specimens at delivery from 27 IgA-deficient (serum IgA < 0.01 g/l) and 15 control women. IgA-deficient women had significantly higher serum IgGl and IgG3 concentrations than control women but 2 of the group had concomitant IgG2/IgG4 deficiency and a further 12 had low IgG4 concentrations (serum IgG4 < 0.025 g/l). Foetal serum also had significantly higher IgGl concentrations than control foetal serum but lower IgG2 and IgG4 levels. Concentrations of IgG subclasses and IgM were measured in breast milk collected on the fifth day postpartum from 19 of these IgA-deficient and 18 control women. Between-group differences in IgG subclass levels resembled those in serum. Compared with serum, proportionally less IgG3 was present in milk in both groups although the contribution of IgG3 to total IgG was not less than that of IgG4. Slightly higher IgM was found in milk from the IgA-deficient mothers.