Malignant mesothelioma, hypoalbuminaemia and the effect of carboplatin/pemetrexed on survival.

AIMS: The incidence of malignant mesothelioma in the UK is increasing. The aim of this study was to determine the prognostic factors and assess the effect of carboplatin/pemetrexed chemotherapy on survival. MATERIALS AND METHODS: Cases of malignant mesothelioma diagnosed between 1998 and 2011 were stratified by year of diagnosis. Factors affecting survival were assessed by Cox's proportional hazards regression. RESULTS: In total, there were 202 new cases of malignant mesothelioma between 1998 and 2011. The age-standardised rate (95% confidence interval) increased from 2.84 (2.06-3.60) to 4.44 (3.50-5.4); P = 0.025. Chemotherapy use has increased since 2006: 52% versus 34% (P = 0.007). The median survival (interquartile range) by year diagnosed was 9 (4.0-21.9) versus 10 (3.8-20.1) months for 1998-2005 versus 2006-2011. Independent predictors of survival [hazard ratio (95% confidence interval)] were: histology, sarcomatoid 2.22 (1.49-3.31) and unspecified non-epithelioid 1.50 (1.06-2.14); Eastern Cooperative Oncology Group performance status ≥3 2.86 (1.64-5.00); hypoalbuminaemia 2.07 (1.47-2.92), carboplatin/pemetrexed chemotherapy 0.56 (0.38-0.80). CONCLUSION: The incidence of mesothelioma is increasing. Adverse prognostic factors include non-epithelioid histology, performance status and hypoalbuminaemia. Overall survival has not improved significantly, but treatment with carboplatin/pemetrexed chemotherapy is associated with a significant survival benefit.

Malignant mesothelioma presenting as a breast mass.

We present a case of a male patient with a breast mass, found to be a malignant mesothelioma. We discuss the diagnostic challenges, the need for heightened awareness in suspected cases, the histological classification of mesotheliomas and the treatments available. We believe this to be the second reported case of a mesothelioma presenting as a breast mass.

Human neutrophil antigen-4a gene frequencies in an Australian population, determined by a new polymerase chain reaction method using sequence-specific primers.

Human neutrophil antigen-4a (HNA-4a) is a high-frequency (99% in the USA) neutrophil antigen, which has recently been linked to a case of alloimmune neonatal neutropenia. We have devised a new polymerase chain reaction sequence-specific primer (PCR-SSP) method to assess HNA-4a genotype, and used it to determine the HNA-4a gene frequencies in an Australian population. The gene frequency was found to be 0.906, which is the same as in the American population. The PCR-SSP genotyping method perfectly correlates with serological phenotyping and is efficient for screening large numbers of samples.

Provider assessment of adherence to HIV antiretroviral therapy.

BACKGROUND: Adherence assessment is an essential component of monitoring HIV antiretroviral therapy. Prior studies suggest that medical providers frequently estimate individual patient adherence inaccurately. OBJECTIVE: We compared provider estimates of nonadherence to antiretroviral therapy with unannounced pill counts and structured patient interviews to determine the accuracy of adherence information obtained by providers and patients. DESIGN, SETTING, AND PARTICIPANTS: Comparison of three adherence measures in homeless or marginally housed persons receiving HIV antiretroviral therapy (n = 45) and their providers (n = 35). MEASUREMENTS: Provider estimate of percentage of pills taken; three successive patient structured reports of number of doses missed in the last 3 days; and three successive unannounced pill counts. RESULTS: 13% (95% confidence interval [CI], 4%-22%) of patients were not following their regimen as directed. Provider-adherence estimate explained only 26% (95% CI, 6%-47%) of the variation in pill count adherence, whereas patient report explained 72% (95% CI, 52%-96%). The sensitivity and specificity of provider estimates of nonadherence, defined as <80% of pills taken by pill count, were 40% and 85%, respectively. The sensitivity and specificity of patient interview were 72% and 95%, respectively. CONCLUSIONS: Provider estimate of adherence was inaccurate whereas structured patient report was more closely related to pill count. Structured assessment over several short intervals may improve accuracy of adherence assessment in clinical practice.

Effects of adaptation on neural coding by primary sensory interneurons in the cricket cercal system.

Methods of stochastic systems analysis were applied to examine the effect of adaptation on frequency encoding by two functionally identical primary interneurons of the cricket cercal system. Stimulus reconstructions were obtained from a linear filtering transformation of spike trains elicited in response to bursts of broadband white noise air current stimuli (5-400 Hz). Each linear reconstruction was compared with the actual stimulus in the frequency domain to obtain a measure of waveform coding accuracy as a function of frequency. The term adaptation in this paper refers to the decrease in firing rate of a cell after the onset or increase in power of a white noise stimulus. The increase in firing rate after stimulus offset or decrease in stimulus power is assumed to be a complementary aspect of the same phenomenon. As the spike rate decreased during the course of adaptation, the total amount of information carried about the velocity waveform of the stimulus also decreased. The quality of coding of frequencies between 70 and 400 Hz decreased dramatically. The quality of coding of frequencies between 5 and 70 Hz decreased only slightly or even increased in some cases. The disproportionate loss of information about the higher frequencies could be attributed in part to the more rapid loss of spikes correlated with high-frequency stimulus components than of spikes correlated with low-frequency components. An increase in the responsiveness of a cell to frequencies > 70 Hz was correlated with a decrease in the ability of that cell to encode frequencies in the 5-70 Hz range. This nonlinear property could explain the improvement seen in some cases in the coding accuracy of frequencies between 5 and 70 Hz during the course of adaptation. Waveform coding properties also were characterized for fully adapted neurons at several stimulus intensities. The changes in coding observed through the course of adaptation were similar in nature to those found across stimulus powers. These changes could be accounted for largely by a change in neural sensitivity. The effect of adaptation on the coding of stimulus power was examined by measuring the response curves to steps in stimulus power before and after exposure to an adapting stimulus. Adaptation caused a loss of information about the mean stimulus power but did not cause any improvement in the coding of changes in stimulus power. The unadapted response of the cells did not show any saturation even at the highest powers used in these experiments.

Information theoretic analysis of dynamical encoding by four identified primary sensory interneurons in the cricket cercal system.

1. The stimulus/response properties of four identified primary sensory interneurons in the cricket cercal sensory system were studied using electrophysiological techniques. These four cells are thought to represent a functionally discrete subunit of the cercal system: they are the only cells that encode information about stimulus direction to higher centers for low intensity stimuli. Previous studies characterized the quantity of information encoded by these cells about the direction of air currents in the horizontal plane. In the experiments reported here, we characterized the quantity and quality of information encoded in the cells' elicited responses about the dynamics of air current waveforms presented at their optimal stimulus directions. The total sample set included 22 cells. 2. This characterization was achieved by determining the cells' frequency sensitivities and encoding accuracy using the methods of stochastic systems analysis and information theory. The specific approach used for the analysis was the "stimulus reconstruction" technique in which a functional expansion was derived to transform the observed spike train responses into the optimal estimate (i.e., "reconstruction") of the actual stimulus. A novel derivation of the crucial equations is presented. The reverse approach is compared with the more traditional forward analysis, in which an expansion is derived that transforms the stimulus to a prediction of the spike train response. Important aspects of the application of these analytical approaches are considered. 3. All four interneurons were found to have identical frequency tuning, as assessed by the accuracy with which different frequency components of stimulus waveforms could be reconstructed with a linear expansion. The interneurons encoded significant information about stimulus frequencies between 5 and 80 Hz, which peak sensitivities at approximately 15 Hz. 4. All four interneurons were found to have identical stimulus/response latencies. The mean latency between a stimulus component and the corresponding elicited spike was 17 ms. All four interneurons also had identical integration times. The integration time, measured by the duration of stimulus, which could affect the probability of spiking, was approximately 50 ms. 5. The accuracy of the encoding can be expressed as a signal-to-noise ratio, where the noise is a scaled difference between the original signal and the best estimate of the signal. Peak signal-to-noise ratios of approximately 1 were obtained for the cells across all stimulus power levels, using only the linear expansion term. Analysis of the data indicated that the consideration of second-order nonlinear transformations of the stimulus would not have increased the calculated encoding accuracy. 6. The encoding accuracy also can be expressed in the information theoretic units of bits/second, which characterizes the information transmission rate of the cell. Bits/second values varied between 10 and 80 for the 22 different cells in our experimental set. The information rate values were highly correlated with the mean spike rates of the interneurons, but were not correlated with the stimulus power levels. However, normalizing the absolute information rates by the mean spike rate in each case yielded a measure of bits/spike that was remarkably invariant across all experiments. The measured bits/spike rate was approximately 1 for all experiments. This result is discussed in the context of recent theoretical studies on optimal encoding. 7. Although the dynamic sensitivities of the four interneurons were identical, their directional sensitivities are known to be orthogonal. Thus the cells are complementary to one another from a functional standpoint: whereas a particular cell will be insensitive to air currents from some directions, one or more of the other three cells will be sensitive to stimuli from those directions...

Children with asthma in schools: an opportunity for "healthy alliances" between health and education authorities.

Head teachers of all primary and secondary schools in County Durham were surveyed during 1994 to investigate school policy and management of children with asthma. Results indicate a need and opportunity to improve asthma care for children at school through healthy alliances between the health and education authorities.

Pulmonary infection with opportunist mycobacteria on Merseyside 1974-1983.

During a 10 year period 49 patients were recorded as having pulmonary infection caused by opportunist mycobacteria. Six different species were identified of which M. kansasii (65%) and M. avium-intracellulare (20%) were the most common. Cough and sputum (82%) or haemoptysis (26%) were frequent symptoms on presentation and over two thirds of patients had pre-existing respiratory disease. Chest radiographs showed predominantly apical disease with the right apex (44%) being twice as commonly affected as the left (22%). In 30% the radiograph showed bilateral disease. Clinicians had an individual approach to treatment with no uniform pattern of drug prescribing. A majority of patients (59%) received rifampicin for at least 9 months and those patients with M. kansasii infection responded well with no bacteriological relapses in 20 patients followed for a mean period of 3.9 years. M. avium-intracellulare, M. malmoense and M. xenopi were less responsive to treatment and in four patients receiving chemotherapy death was attributed to mycobacterial infection.

Pulmonary infection with Mycobacterium malmoense: a report of 4 cases.

Four cases of pulmonary infection with Mycobacterium malmoense are presented. The clinical features are described and the significance of this organism in producing pulmonary disease is discussed.

Acute pancreatitis and Cushing's syndrome.

A case of acute necrotizing pancreatitis in a 53-year-old man with an ectopic adrenocorticotrophin (ACTH) producing bronchial carcinoma is described. The aetiology of acute pancreatitis in relation to steroid therapy and malignancy is discussed and it is suggested that excess endogenous steroid production may also cause acute pancreatitis.

The effect of exercise on the deposition of an inhaled aerosol.

We investigated the regional deposition in the lungs, of an inhaled submicron aerosol at rest and during exercise in 13 normal volunteers of whom 5 were cigarette smokers. The degree of exercise (VO2 approximately 2 L/min) was chosen to simulate moderately heavy physical labour. Tracheobronchial and alveolar components of deposition were measured by comparing images immediately after inhalation of aerosol and 24 h later when mucociliary clearance was complete. At rest almost all deposition was alveolar (97%). The increase in total deposition on exercise was of similar order to the increase in ventilation. On exercise regional alveolar deposition became more even, although basal still exceeded apical deposition. Tracheobronchial deposition on exercise was increased in all zones but particularly in the upper zones, thereby contrasting with the base to apex gradient of parenchymal deposition. These changes were exaggerated in the smokers. The increased upper zone tracheobronchial deposition may have implications in regard to the pathogenesis of diseases caused by the inhalation of dusts and fumes.

Influence of cardioselectivity and respiratory disease on pulmonary responsiveness to beta-blockade.

The effects on ventilation of the non-selective beta-blocker propranolol, and the relatively cardioselective beta-blocker, metoprolol, were compared in a randomized single-blind crossover study in 16 patients with asthma, bronchitis and emphysema (American Thoracic Society criteria). Group I had "fixed" airways disease with less than 20% improvement in FEV1 following inhaled salbutamol 5 mg by nebuliser. Group II had "reversible" obstruction, greater than 20% improvement. Bronchodilator therapy was withheld for 24 h with the exception of aerosols which were permitted until 12 h before study. After control observations on each of 2 study days, each patient received cumulative doses of propranolol (maximum 170 mg) and metoprolol (maximum 187.5 mg). Ventilatory function (FEV1, FVC, FEV1%) was assessed at 0, 2, 4, 6 and 8 h. In Group I, 2 patients were unable to complete the study. One patient became dizzy with propranolol 70 mg but tolerated metoprolol 187.5 mg. One patient developed wheeze with propranolol 15 mg but tolerated metoprolol 187.5 mg. Metoprolol was tolerated in all 8 patients with "fixed" disease, although FEV1 was reduced by more than 30% in 1 patient. Three patients in Group II did not complete the study because of wheezing following propranolol 10 mg, metoprolol 37.5 mg; propranolol 17.5 mg, metoprolol 37.5 mg; propranolol 45 mg, tolerated metoprolol 187.5 mg respectively. Wheezing responded in all cases to inhaled isoprenaline. The response to either propranolol or metoprolol was unpredictable in patients with "reversible" disease. When wheezing occurred in this group, it developed following small, potentially subtherapeutic doses of each drug. Although metoprolol was better tolerated, the practical benefit of cardioselectivity in those patients with reversible airways disease was negligible.

Histamine bronchial challenge: effect on regional ventilation and aerosol deposition.

We studied regional changes in ventilation and aerosol deposition after histamine challenge in six patients with asthma and two with rhinitis and a history of wheezing. All were known to have bronchial hyperreactivity and all showed an increased response to histamine. Ventilation and aerosol deposition studies, using xenon-133 and an aerosol of sulphur colloid tagged with technetium 99m, were performed while they were sitting. Before administration of histamine radioaerosol scintiscans were abnormal in five of six patients; after histamine challenge all were abnormal and central deposition was significantly greater in all of them. The decrease in aerosol penetration correlated with the percentage decrease in FEV1, indicating that the efficiency of aerodynamic filtration depends on the degree of airway narrowing. In six of the eight subjects the distribution of ventilation changed from predominantly basal to predominantly apical after histamine, which suggests the airways response was greater, at least initially, in the better ventilated regions. This indicates a close relationship between regional ventilation and the site of histamine deposition and has implications for the delivery of aerosolised agents in general.