Survival, quality-adjusted survival, and other clinical end points in older advanced non-small-cell lung cancer patients treated with albumin-bound paclitaxel.

BACKGROUND: This analysis compared the quality-adjusted survival and clinical outcomes of albumin-bound paclitaxel+carboplatin (nab-PC) vs solvent-based paclitaxel+carboplatin (sb-PC) as first-line therapy in advanced non-small-cell lung cancer (NSCLC) in older patients. METHODS: Using age-based subgroup data from a randomised Phase-3 clinical trial, nab-PC and sb-PC were compared with respect to overall response rate (ORR), overall survival (OS), progression-free survival (PFS), quality of life (QoL), safety/toxicity, and quality-adjusted time without symptoms or toxicity (Q-TWiST) with ages ⩾60 and ⩾70 years as cut points. RESULTS: Among patients aged ⩾60 years (N=546), nab-PC (N=265) significantly increased ORR and prolonged OS, despite a non-significant improvement in PFS, vs sb-PC (N=281). Nab-PC improved QoL and was associated with less neuropathy, arthralgia, and myalgia but resulted in more anaemia and thrombocytopenia. Nab-PC yielded significant Q-TWiST benefits (11.1 vs 9.8 months; 95% CI of gain: 0.2-2.6), with a relative Q-TWiST gain of 10.8% (ranging from 6.4% to 15.1% in threshold analysis). In the ⩾70 years age group, nab-PC showed similar, but non-significant, ORR, PFS, and Q-TWiST benefits and significantly improved OS and QoL. CONCLUSION: Nab-PC as first-line therapy in older patients with advanced NSCLC increased ORR, OS, and QoL and resulted in quality-adjusted survival gains compared with standard sb-PC.

"Ethnic" variation in childhood lung function may relate to preventable nutritional deficiency.

UNLABELLED: This study aimed to define the differences in lung function between British Caucasian and rural eastern Indian children, and to test the hypothesis that nutrition could account for such "ethnic" variation. To exclude confounders, a rural Indian setting was identified and children were screened for respiratory illness before lung function and nutritional characteristics were measured. Regression equations for this population have already been published. In this study, the lung function differences between rural eastern Indian (n=391) and mean predicted lung function for Caucasian children were characterized, matched for height and sex. In addition, stepwise multiple regression models were fitted to investigate the relative associations of lung function differences with body mass index (BMI), occipitofrontal circumference and age. Although the largest differences in the forced expiratory volume in 1 s (FEV1) [girls 28.7 (27.3-30.1), boys 23.4 (22.2-24.6)] and forced vital capacity [girls 27.9 (26.4-29.4), boys 30.7 (29.6-31.9)] [values as mean difference in % predicted (95% confidence intervals)] ever reported between two populations were observed, differences in peak expiratory flow rate (PEFR) were small. BMI was strongly associated with inter-racial differences for FEV1 for both sexes (boys beta = -0.227, girls beta = -0.353. p < 0.001) and PEFR for girls (beta = -0.200, p < or = 0.05) (beta = standardized coefficient). CONCLUSION: Preventable nutritional factors may play a causal role in determining the FEV1 differences between rural Indian and Caucasian children. As peak FEV1 in youth influences respiratory morbidity in later life, it is important to define specific nutrient deficiencies that may relate to poor FEV1 growth in these children.

Femoral head measurement in hemiarthroplasty: assessment of interobserver error using 3 measuring systems.

We have assessed the consistency of measurement of femoral head circumference using 3 standard measuring instruments used in hemiarthroplasty of the hip. Fifty femoral heads were independently sized by ten independent observers using a caliper, a half circular measuring template, each allowing measurement to the nearest millimeter. We found significantly greater variance of the results using the half-circular templates (p=0.001) and the calipers (p=0. 011) compared with the full circular measuring templates. Measurement with calipers underestimated femoral head size by 0.72 mm compared with full circular measuring templates (p=0.02). Insertion of an undersized hemiarthroplasty head is a cause of increased point loading of the acetabulum and may result in increased rates of acetabular erosion. The use of full circular measurement templates is recommended as the most consistent method for head sizing in hemiarthroplasty of the hip.

Cu metabolism in the liver.

This paper has, given some idea of our concepts of the processes involved in the transport of Cu across cell membranes in the liver, which we have summarised in Fig 1. Cu(II)His2 is reduced to Cu(I). This is transported across the membrane, re-oxidised, either before or after binding to glutathione (Freedman et al., 1989) or HAH1 (Klomp et al., 1997), binds to SAHH, and donates Cu(II) to the ATPase. It is very interesting that cells which are very diverse from an evolutionary point of view still use very similar methods to handle the metal. Whether regulation of transport is also the sam remains to be seen. We would guess that, although there will be strong similarities, there will also be very significant differences, reflecting the different environments seen by different tissues in mammalian cells and given the different requirements of the tissues.

Prediction of lung function in the inadequately nourished.

BACKGROUND: In animal models, nutritional deficiency leads to profound qualitative changes in the lung beyond an effect on organ size. Although lung growth is non-isotropic, predictive values for spirometric lung function in children are corrected for height alone. Prediction of lung function should consider isotropic growth and nutritional status concurrently. AIM: To establish whether nutritional status influences lung function following the exclusion of the effect of isotropic growth. METHODS: Nutritional status (weight, body mass index, mid-upper arm circumference, and subscapular and triceps skinfold thicknesses) was assessed, and lung function (forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow rate (PEFR) was measured in 391 healthy school age children with normal respiratory history and examination in a rural setting in West Bengal, India. RESULTS: Lung function normalised for sitting height and stature correlated significantly with indices of nutrition in both sexes. Adding weight as an independent variable to sitting height, new reference prediction equations for FEV1, FVC, and PEFR were calculated. CONCLUSIONS: Nutritional differences influence qualitative aspects of lung development in childhood beyond simple isotropic lung growth. Prediction of lung function must take account of these differences if change as a result of disease is to be accurately measured. The identification and correction of relevant dietary deficiencies might help to improve lung function in children.

Physiologic function of the Wilson disease gene product, ATP7B.

The genes responsible for Wilson disease and Menkes syndrome have been cloned and identified as copper ATPases. These enzymes form part of a large family of transporters, the P-type ATPases. Although copper ATPases share strong structural similarities with these other pumps, comparatively little is known about their physiologic function. In this review, we examine data relating to the Wilson disease protein, ATP7B, in the liver. We present evidence suggesting that ATP7B is located intracellularly, together with data suggesting that, at least in part, ATP7B may also be found on the canalicular membrane. We also examine the form of copper that the transporter recognizes. We then review data on the Long-Evans Cinnamon rat, a model for Wilson disease, and discuss what effect the Wilson disease mutation has on copper transport. Finally, we conclude that, although we have made major advances in our understanding of copper metabolism in the liver, there are still many questions awaiting answers.

ATP-dependent copper transporter, in the Golgi apparatus of rat hepatocytes, transports Cu(II) not Cu(I).

The Wilson disease adenosinetriphosphatase (ATPase; ATP7B) is believed to bind copper as Cu(I). We provide evidence to suggest that the ATPase actually transports Cu as Cu(II). When the copper is presented to rat liver microsomes as Cu(I), virtually all uptake is ATP independent. If the copper is presented as copper oxalate [Cu(II)], total uptake is reduced to approximately 10% of Cu(I) levels, but ATP-dependent uptake rises, both as a proportion of total uptake and in absolute terms. The reducing agent vitamin C and the Cu(I) chelator bathocuproine both override the effect of oxalate. The data indicate that there are two transporters in the microsomes, an ATP-independent Cu(I) transporter and an ATP-dependent Cu(II) pump. The activity of the Cu(I) transporter correlates most strongly with alkaline phosphatase, suggesting that it is derived from plasma membrane contamination. Cu(II) ATP-dependent transport correlates only with beta-1, 4-galactosyltransferase, which indicates that it is located in the Golgi apparatus.

Colonic stricture in cystic fibrosis unmasked by successful transjugular intrahepatic portosystemic stent shunt (TIPSS).

TIPSS was successfully performed in a 10-year-old female cystic fibrosis (CF) patient with bleeding gastric varices due to portal hypertension; precipitation of portosystemic encephalopathy later unveiled the presence of a latent colonic stricture associated with high potency pancreatic enzymes. The unusual sequence of events resulting from the co-existence of two CF pathologies are described, and the implications of treatment discussed.

Characterization of zinc uptake and its regulation by arachidonic acid in fetal type II pneumocytes.

In freshly isolated fetal guinea pig type II pneumocytes, zinc uptake is time and temperature dependent. Two pathways of uptake exist, resulting in a rapid phase that reaches a steady state within 30 s and a slower linear phase that does not attain a steady state within 60 min. Both processes exhibit saturation kinetics. The rapid phase has a maximal zinc uptake of 60.7 +/- 9.3 pmol.10(6) cells-1.30 s-1 and an apparent affinity (Kt) of 13.7 +/- 5.4 microM. The maximum velocity of uptake (Vmax) of the slower phase is 24.6 +/- 1.9 pmol.10(6) cells-1.min-1 with a Kt of 22.0 +/- 3.6 microM. Epinephrine, terbutaline, dibutyryl adenosine 3',5'-cyclic monophosphate, and dexamethasone have no significant effect on zinc uptake, while arachidonic acid (AA) stimulates. Dose-response data of AA-stimulated zinc uptake gives an apparent K0.5 of 0.42 +/- 0.01 microM and a Hill coefficient of 1. The maximal uptake in the rapid phase is significantly increased to 146.8 +/- 12.4 pmol.10(6) cells-1.30 s-1 and in the slow phase, the Vmax for zinc uptake is also significantly increased to 33.0 +/- 1.8 pmol.10(6) cells-1.min-1 by 10 microM AA. However, the Kt values in both processes remain unchanged after AA stimulation. The effect is not mediated by either leukotrienes or prostaglandins but can be mimicked by other unsaturated fatty acids.