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Global inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia.

This study was designed to assess the cost-effectiveness of erlotinib compared with docetaxel in the second-line management of advanced non-small-cell lung cancer (NSCLC) within the UK National Health Service (NHS). A health-state transition model, based on two randomized phase III studies of erlotinib or docetaxel versus best supportive care, was used to estimate total direct costs, quality-adjusted life years (QALYs) and the subsequent net monetary benefit. Erlotinib was associated with a reduction in total costs (£13 730 versus £13 956) and improved outcomes (total QALYs of 0.238 versus 0.206) compared with docetaxel. Sensitivity analyses demonstrated the robustness of this analysis. In summary, erlotinib appeared to generate similar overall survival, an increase in QALYs and a small reduction in total NHS costs compared with docetaxel, due to lower adverse event and drug administration costs. Consequently, from a health economics perspective for the treatment of relapsed stage III - IV NSCLC patients in the UK, erlotinib has advantages over docetaxel.

The regulatory pathways involved in the rapid response of the AP-1 transcription factor, c-fos, to mechanical load in human primary osteoblast-like (HOB) cells and the human MG-63 bone cell line were investigated using a four-point bending model. HOB and MG-63 cells showed upregulation of c-fosexpression on fibronectin and collagen type I substrates; however, MG-63 cells did not respond on laminin YIGSR substrates. Addition of cytochalasin D and Arg-Gly-Asp peptides during loading did not inhibit the response, whereas addition of β1-integrin antibodies inhibited the load response. The role of Ca2+signaling has been demonstrated by blocking upregulation with addition of 2 mM EGTA, which chelates extracellular Ca2+, and gadolinium (10 μM), which inhibits stretch-activated channels. Addition of the Ca2+ionophore A-23187 induced upregulation without loading; however, addition of nifedipine (10 μM), the L-type channel blocker, failed to prevent the load response. Inhibitors of downstream pathways indicated the involvement of protein kinase C. Our results demonstrate a key involvement of Ca2+signaling pathways and integrin binding in the c-fosresponse to mechanical strain.

A randomized, double-blind, double-dummy protocol was used to compare the safety and efficacy of beclomethasone dipropionate (BDP) delivered by a novel dry powder inhaler (DPI, Clickhaler®) or by a pressurized metered-dose inhaler (MDI) plus spacer. There was a four-week run-in period, completed by 240 adult patients, who received BDP via an MDI. Patients with stable asthma were then randomized into a 12-week treatment period and received BDP (<2 mg/day via DPI or MDI). There were no significant differences in morning peak expiratory flow (PEF) (primary endpoint), evening PEF, overall daytime or nighttime symptom scores, or lung function parameters (forced expiratory volume in 1 sec, forced vital capacity) between DPI and MDI. The safety profiles were similar and patient acceptability for Clickhaler was high. In conclusion, BDP administered via Clickhaler was found to be clinically equivalent to an optimally used MDI. Patients with stable asthma currently receiving BDP via MDI may be effectively switched to treatment via Clickhaler DPI.

The performance of dry powder inhaler (DPI) devices, particularly reservoir DPIs, may be influenced by environmental conditions. This study compared the bronchodilator efficacy and in vitro aerosol characteristics of salbutamol, delivered via a novel reservoir DPI (Clickhaler®) and a conventional pressurized metered-dose inhaler (MDI) before and after use of the DPI in clinical practice. Following a screening visit, patients received cumulative doses of salbutamol (100, 200, and 400 ug) via DPI or MDI on separate days in a double-blind, crossover design before and after a 4-week period, during which the DPI was used as the patients' first-line bronchodilator. Lung function responses (forced expiratory volume in 1 sec [FEV1], forced vital capacity [FVC], and peak expiratory flow [PEF]) to salbutamol delivered by DPI and MDI and in vitro aerosol characteristics were not significantly different before and after the period of DPI patient use. DPI performance, assessed in vivo and in vitro, is maintained following an extended period of patient use.

The monitoring of the precision and accuracy of analyses carried out in clinical chemistry laboratories may be performed by quality control programs. Such quality control programs may be operated in individual laboratories and a plethora of regional, national, and international programs, proficiency testing schemes, and quality assurance surveys may assist in the evaluation of performance with respect to either other laboratories or to empirically derived goals.

A number of colorimetric methods, particularly enzyme activity assays, are usually standardised using calculation factors based on the molar absorptivity of a principle reactant or product. Such methods are subject to long-term variation. The relationship between long-term variation in results and instrument variables affecting calculation factors has not been quantitated. In this study, we have shown that, on a centrifugal analyser having a within-run coefficient of variation of less than 1%, instrument variables affecting calculation factor alone could result in changes in results of up to 8·5% over 75 days. We therefore advocate daily use of a solution of potassium dichromate to monitor instrument variables that can independently affect calculation factors and within-run imprecision. This procedure is useful for maintaining long-term performance and for differentiating problems of instrumental or chemical origin.

We previously showed that alterations in the enhancer sequence of polyomavirus DNA can alter both the level and the organ specificity of viral DNA replication during the acute phase of infection of newborn mice (R. Rochford, B. A. Campbell, and L. P. Villarreal, J. Virol. 64:476-485, 1990). In this study, we examined whether these enhancer sequence alterations can also affect polyomavirus replication during the persistent phase of infection in vivo. After infection of newborn mice with a mixture of three enhancer variants, the individual organs could select for enhancer-specific viral DNA replication during both the acute and the persistent phases of infection. Contrary to expectations, the ability of some variants to establish a high-level acute infection in some organs (e.g., the pancreas) did not necessarily lead to a persistent infection in those organs. Thus, enhancers can affect acute and persistent infections differently. In addition, some enhancer variants tended to establish a high-level persistent infection in the kidneys immediately following an acute infection; however, in all cases considerable histopathology was associated with these elevated long-term infections, and these mice were always runty. A persistent infection in the kidneys thus appears able to exist in two distinguishable states, a high-level pathological state and a low-level nonpathological state, which can be affected by the viral enhancer sequence.

This paper investigates the statement by Zachariah (The Antiseptic, 1980, Vol. 77, pp. 87-88) that low dose verapamil was effective in controlling stuttering in a majority of patients when compared to placebo. Fourteen subjects were studied over 6 weeks through a double-blind trial which looked at the speech symptoms, physiological changes and individual subjective ratings of speech. No significant differences were found between the periods of verapamil treatment and placebo.

OBJECTIVE: To study the time course and prediction of responses to reassurance after gastroscopy showing no serious illness. DESIGN: Selection of consecutive patients were assessed before gastroscopy, immediately after reassurance, and at follow up at 24 hours, 1 week, 1 month, and 1 year. Responses of subgroups of patients identified as high, medium, and low health anxiety by the health anxiety questionnaire were analysed. SETTING: Endoscopy clinic in a general hospital. INTERVENTION: Oral reassurance that there was "nothing seriously wrong." SUBJECTS: One consultant physician and 60 patients aged 18-74 referred for gastroscopy. MAIN OUTCOME MEASURES: Physician's and patients' ratings of the extent of the reassurance and patients' ratings of their anxiety about their health and of their illness belief. RESULTS: There was good agreement between the patients and the physician about whether reassurance had been given. Health anxiety and illness belief decreased markedly after reassurance. Patients with high health anxiety showed a significant resurgence in their worry and illness belief at 24 hours and 1 week, and these levels were maintained at 1 months and 1 year later. Patients with medium levels of health anxiety showed a reduction in worry and illness belief after reassurance, and this was generally maintained during follow up. Patients with low health anxiety maintained low levels of health worry and illness belief throughout the study. Partial correlation analyses showed that the levels of worry and illness belief after reassurance were predicted by the health anxiety questionnaire. This measure also had predictive value beyond that of a measure of general anxiety. CONCLUSIONS: Medical reassurance results in a reduction of worry about health and of illness belief, but this may be very short term. Measurable individual differences in health anxiety can be used to predict the response to reassurance.

A radioimmunoassay for neuron specific enolase (NSE), a marker of neuroendocrine differentiation, has been evaluated in small cell lung cancer (SCLC). In untreated patients 25/38 (68%) with localized SCLC had raised blood levels of NSE (greater than 13 ng ml-1), in extensive disease 34/39 (87%) patients had raised NSE levels. In patients with non-small cell lung cancer (NSCLC) the serum levels were raised in 16/94 (17%). In extensive tumours of non-pulmonary origin NSE levels were increased in 24/116 (20%) patients. Longitudinal studies indicated a good correlation between the response to chemotherapy and fall of NSE levels. Tumour progression was accompanied by a rising NSE in 25/29 patients, with doubling times of 7-90 days. In patients with progression with a normal NSE the recurrence was a NSCLC. Cerebral metastases occurring as the only recurrence during clinical complete remission were not accompanied by a rise of NSE. Serum NSE levels provides a valuable monitor for SCLC during and after chemotherapy.

In the presence of the antibiotic tunicamycin (TM), glycosylation of herpes simplex virus glycoproteins is inhibited and non-glycosylated polypeptides analogous to the glycoproteins are synthesized (Pizer et al., J. Virol. 34:142-153, 1980). The synthesis of viral proteins and DNA occurs in TM-treated cells. By electron microscopy, nucleocapsids can be observed both in the nucleus and the cytoplasm of TM-treated cells; a small number of enveloped virions were observed on the cell surface. Analyses of the proteins in partially purified virus readily detects viral glycoproteins in the control cells, but neither glycoproteins nor nonglycosylated polypeptide analogs were observed in the virus prepared from TM-treated cells. By labeling the surface of infected cells with 125I, viral glycoproteins were detected as soon as 90 min after infection even when protein synthesis was inhibited with cycloheximide and glycosylation was blocked with TM. Labeling the proteins synthesized in infected cells with [35S]methionine showed that the surface glycoproteins detected in the cycloheximide- and TM-treated cells were not synthesized de novo after infection, but were placed on the cell surface by the infecting virus. Studies with metabolic inhibitors and a temperature-sensitive mutant blocked early in the infectious cycle showed that glycoproteins gA/gB and gD were synthesized soon after infection, but that the synthesis of gC was delayed. Under conditions of infection, in which gC and its precursor pgC are not produced, we have been able to observe the relationships between the glycosylated polypeptides that correspond to pgA/pgB and the nonglycosylated analog made in the presence of TM.

A crossover study was carried out to compare the acceptability and efficacy of 8 mg twice daily controlled release salbutamol with 525 or 700 mg twice daily aminophylline in patients with reversible obstructive airways disease. Patients were randomly allocated into two groups to determine the treatment order. A 2-week run-in period was used to titrate the aminophylline dosage, followed by a crossover phase of two 4-week treatments. A total of 68 patients, aged 20 − 75 years, entered the study and 39 (57%) completed it. The two drugs differed in the pattern and severity of their side-effects. Of the 15 patients withdrawn because of severe adverse events, 12 were unable to tolerate treatment with aminophylline. There were no statistically significant differences between the treatments for lung function tests measured at the clinic, peak expiratory flow rate recorded by the patients, frequency (or severity) of asthma symptoms or the use of relief medication. Patients completing the study expressed a preference for controlled release salbutamol in 17/25 (68%) cases.

RNA transfer experiments (Northern analyses) were used to localize polyadenylated mRNA species made after herpes simplex virus type 1 infection to EcoRI and BamHI fragments and subfragments from the short unique region of the herpes simplex virus type 1 (KOS) genome. Three predominant early mRNAs of 2.5, 1.3, and 0.9 kilobases map in the BamHI J fragment. A detailed restriction map of the BamHI J fragment was constructed.

An evaluation of a colorimetric kit method for the determination of inorganic phosphate (Pierce Phosphorus Auto/Stat Kit) is described. The within-batch and between-batch precisions were shown to fulfil current criteria, and recovery experiments, linearity studies, analyses of quality control materials, and studies of possible interfering substances evidenced good accuracy. Comparison of the results obtained on samples from patients with those obtained by the vanadate/molybdate continuous-flow method showed that the test method had a comparative positive bias. The use of a calibration reference serum as standard is recommended. The kit method is technically simple, requiring no protein precipitation, and analyses can be performed rapidly.

Objectives. We tested the hypothesis that compared with patients with low health anxiety those with high health anxiety would perceive and recall reassurance given by a physician as less reassuring than the physician reported giving.

For analysis of calcium, most clinical chemists choose either a kit method, an SMA 12/60 or an atomic absorption spectrophotometric (AAS) method. In this laboratory AAS is preferred but in routine screening, serum calciums are analysed on the SMA 12/60. A need exists in the clinical laboratory for a simple inexpensive instrument capable of analysing calcium quickly and accurately.

Serum samples were collected from 115 small-cell lung cancer patients before each course of chemotherapy and during follow-up. Levels of neuronspecific enolase (NSE) were measured and compared to the clinical assessments of the course of the disease, which were done by the responsible physician without knowledge of NSE-values. The predictive accuracy of an increase or decrease of NSE for a major response (CR+PR), SD or PD was 98%. Importantly no falsepositive rises of NSE were observed. On the basis of this large number of data it seems justified to conclude that in common clinical practice the treatment of small-cell lung cancer patients can be monitored by serial measurements of NSE alone.