Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer.

PURPOSE: To evaluate the effect of BLP25 liposome vaccine (L-BLP25) on survival and toxicity in patients with stage IIIB and IV non-small-cell lung cancer (NSCLC). Secondary objectives included health-related quality of life (QOL) and immune responses elicited by L-BLP25. PATIENTS AND METHODS: Patients with an Eastern Cooperative Oncology Group performance status of 0 to 2 and stable or responding stage IIIB or IV NSCLC after any first-line chemotherapy were prestratified by stage and randomly assigned to either L-BLP25 plus best supportive care (BSC) or BSC alone. Patients in the L-BLP25 arm received a single intravenous dose of cyclophosphamide 300 mg/m2 followed by eight weekly subcutaneous immunizations with L-BLP25 (1,000 microg). Subsequent immunizations were administered at 6-week intervals. RESULTS: The survival results indicate a median survival time of 4.4 months longer for patients randomly assigned to the L-BLP25 arm (88 patients) compared with patients assigned to the BSC arm (83 patients; adjusted hazard ratio [HR] = 0.739; 95% CI, 0.509 to 1.073; P = .112). The greatest effect was observed in stage IIIB locoregional (LR) patients, for whom the median survival time for the L-BLP25 arm has not yet been reached compared with 13.3 months for the BSC arm (adjusted HR = 0.524; 95% CI, 0.261 to 1.052; P = .069). No significant toxicity was observed. QOL was maintained longer in patients on the L-BLP25 arm. CONCLUSION: L-BLP25 maintenance therapy in patients with advanced NSCLC is feasible with minimal toxicity. The survival difference of 4.4 months observed with the vaccine did not reach statistical significance. In the subgroup of patients with stage IIIB LR disease, a strong trend in 2-year survival in favor of L-BLP25 was observed.     

Book reviews

History

The End of History and the Last Man By Francis Fukuyama. Hamish Hamilton, London, 1992, 418 pp., £20.00, ISBN 0–24–1301–1

Aeskulap oder Mars? [Asdepius or Mars] (subtitle: Doctors against War) Edited by T.M. Ruprecht and C. Jenssen. (In German). Donat Verlag, Bremen, 1991, 604pp., 48.00DM, ISBN 3–924444–51‐X.

The Gulf War

Hidden Casualties, Volume II: The Environmental, Health and Political Consequences of the Persian Gulf War Edited by Saul Bloom, John M. Miller and Philippa Winkler, with Ross Mirkarimi. ARC/Arms Control Research Center, 942 Market St, Suite 202, San Francisco CA 94102, USA, 1993, 350pp.

Medicine and War

Wounded Healthy Cities: Searching for Health and Human Dignity A report by the Croatian Healthy Cities Network. Compiled by Ivana Eterovi?, Selma Sogori?, and Slobodan Lang. Edited by John Middleton. Sandwell Public Health Publications, 1992, PO Box 1953, Lyndon, West Bromwich, West Midlands, B71 4NA, pp. 68, £5.95 incl. p&;p, ISBN 0–9517035–4–4.

Public Health

Health through Public Policy, the Greening of Public Health Edited by Peter Draper. Greenprint, London, 1991, x + 258 pp., £9.99, ISBN 1–85425–045–0.

Economics

The Culture of Contentment By John Kenneth Galbraith. Sinclair Stevenson, London, 1992, 195pp., £14.95, ISBN 1–85619–147–8.

Beyond the Limits: Global Collapse or a Sustainable Future By Donella Meadows, Dennis Meadows and Jorgen Randers. Earthscan, London, 1992, xix + 300 pp., £19.95, ISBN 1–85383–130–1 (hbk), £11.95, ISBN 1–85383–131‐X (pbk).

Human Rights

Refugees: Rationing the Right to Life By David Keen. Zed Books, London, 1992, 86pp., £29.9S(hbk), ISBN 1–85649–091–2, £9.95(pbk), ISBN 1–85649–092–0.

Deadly Silence: Black Deaths in Custody Institute of Race Relations, London, 1991, 75pp., £4 (pbk), ISBN 085001–038–1.

Torture and Its Consequences: Current Treatment Approaches Edited by Metin Ba?o?lu. Cambridge University Press, Cambridge, 1992, xxiii + 527pp., £55.00, ISBN 0–521–39299–3

Militarism and the Environment

Taking Stock: The Impact of Militarism on the Environment Working Group on Militarism and the Environment. Science for Peace, 1992, 30pp., Can$ 4.00 (available from WGME, University College, University of Toronto, Ontario, Canada M5S 1A1).

AIDS

The AIDS Epidemic: Economic, Political and Security Implications By Alan Whiteside and David FitzSimons. Research Institute for the Study of Conflict and Terrorism, London, 1992, 43pp., £9.00, ISSN 0069–8792 (available from 136 Baker Street, London W1M 1FH)     

An exploration of nurse-physician perceptions of collaborative behaviour

Interprofessional collaboration is a key element in providing safe, holistic patient care in the acute care setting. Trended data at a community hospital indicated opportunities for improvement in collaboration on micro, meso, and macro levels. The aim of this survey study was to assess the current state of collaboration between frontline nurses and physicians at a non-academic acute care hospital. A convenience sample of participants was recruited with a final respondent sample of 355 nurses and 82 physicians. The results indicated that physicians generally perceived greater collaboration than nurses. Physician ratings did not vary by primary practice area, whereas nurse ratings varied by clinical practice area. Nurse ratings were the lowest in the operating room and the highest in the emergency department. Text-based responses to an open-ended question were analysed by role and coded by two independent research teams. Emergent themes emphasised the importance of rounding, roles, respect, and communication. Despite recognition of the need for improved collaboration and relational behaviours, strategies to improve collaborative practice must be fostered at the meso level by organisational leaders and customised to address micro-level values. At the study site, findings have been used to address and improve collaboration towards the goal of becoming a high reliability organisation.     

Cyclosporin Treatment Improves Skin Findings in Omenn Syndrome

Omenn syndrome is a combined immunodeficiency characterized by a generalized erythematous skin rash, enlarged lymph nodes, hepatosplenomegaly, severe susceptibility to infections, eosinophilia, and hyperimmunoglobulinemia E. A 3‐month‐old girl was admitted to our hospital with a history of recurrent sepsis. Physical examination revealed severe erythroderma, hepatosplenomegaly, lymphadenopathy, and failure to thrive. Laboratory findings revealed leukocytosis, lymphocytosis with high CD3 T‐cells, a high CD4:CD8 ratio, absence of CD19 B‐cells, high eosinophil count, and low immunoglobulin levels. A heterozygote RAG1 gene mutation was found. She had itchy, scaling, ichthyosiform erythroderma and protracted diarrhea. Cyclosporin treatment up to 10 mg/kg effectively resolved erythroderma and lowered total eosinophil counts, and she gained weight during treatment. Since extensive erythroderma with generalized itching causes patient discomfort in Omenn syndrome, cyclosporin treatment can be considered while waiting for treatment with hematopoietic stem cell transplantation.     

Estimating genome conservation between crop and model legume species

Legumes are simultaneously one of the largest families of crop plants and a cornerstone in the biological nitrogen cycle. We combined molecular and phylogenetic analyses to evaluate genome conservation both within and between the two major clades of crop legumes. Genetic mapping of orthologous genes identifies broad conservation of genome macrostructure, especially within the galegoid legumes, while also highlighting inferred chromosomal rearrangements that may underlie the variation in chromosome number between these species. As a complement to comparative genetic mapping, we compared sequenced regions of the model legume Medicago truncatula with those of the diploid Lotus japonicus and the polyploid Glycine max. High conservation was observed between the genomes of M. truncatula and L. japonicus, whereas lower levels of conservation were evident between M. truncatula and G. max. In all cases, conserved genome microstructure was punctuated by significant structural divergence, including frequent insertion/deletion of individual genes or groups of genes and lineage-specific expansion/contraction of gene families. These results suggest that comparative mapping may have considerable utility for basic and applied research in the legumes, although its predictive value is likely to be tempered by phylogenetic distance and genome duplication.     

Association of interleukin (IL)-4 gene intron 3 VNTR polymorphism with multiple sclerosis in Turkish population

Objective

Genetic risk factors are known to contribute to the etiology of multiple sclerosis (MS). Interleukin (IL)-4 gene polymorphisms have been associated with immune-mediated diseases. The aim of this study was to explore the frequency of IL-4 gene intron 3 VNTR (variable number tandem repeat) polymorphism in a cohort of Turkish patients with MS.

Methods

The study included 125 patients with MS and 160 healthy controls. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) analyses for the IL-4 gene intron 3 VNTR polymorphism.

Results

The distribution of genotype and allele frequencies of IL-4 gene intron 3 VNTR polymorphism was statistically different between MS patients and control group (p = 0.003 and p = 0.002, respectively). There were no statistically significant association between IL-4 VNTR polymorphism and clinical and demographical characteristics of MS patients.

Conclusion

The results of this study suggest that intron 3 VNTR polymorphism of the IL-4 gene was positively associated with predisposition to develop MS in Turkish population.     

Global and specific transcriptional repression by the histone H3 amino terminus in yeast

The yeast CHA1 promoter is activated in the presence of serine or threonine. Activation requires the Cha4p activator, and it results in perturbation of a nucleosome that incorporates the TATA element under noninducing conditions. We show that in yeast lacking the amino terminus of histone H3, the promoter is constitutively active and the chromatin is concomitantly perturbed. This derepression occurs in the absence of elevated intracellular levels of serine or threonine and is not observed in cells lacking Rpd3p, Tup1p, or the amino terminus of histone H4. Furthermore, derepression in the absence of the H3 amino terminus requires the primary activator of this promoter, Cha4p, which we show by chromatin immunoprecipitation to be constitutively bound to the CHA1 promoter in WT yeast. Thus, the H3 amino terminus is required to prevent Cha4p from activating CHA1 in the absence of inducer. We also present results of a microarray experiment showing that the H3 amino terminus has a substantial repressive effect on a genome-wide scale.     

Multiple fistulae connecting the right coronary artery to the coronary sinus

Right coronary artery to coronary sinus fistula is a rare anomaly. We present a unique case of an adult patient with multiple fistulae from the right coronary artery draining into the coronary sinus near the posterior left atrium-left ventricle junction, first suspected by transthoracic two-dimensional echocardiography. The multiple openings were not seen by any invasive or noninvasive techniques and were noted only at the time of surgery. To our knowledge, this is the first case of multiple fistulae connecting the right coronary artery to the coronary sinus that has been reported in the English literature.     

Aerobic exercise improves oxidant-antioxidant balance in patients with rheumatoid arthritis

[Purpose] Although oxidative stress is known to be present in rheumatoid arthritis (RA), the effects of exercise on oxidative parameters are unknown. The aim of this study was to investigate the effects of acute aerobic exercise on serum oxidant and antioxidant levels in patients with RA. [Subjects and Methods] Sixteen patients with RA and 10 age-matched healthy volunteers participated in this study. All participants wore polar telemeters and walked on a treadmill for 30 minutes at a speed eliciting 60–75% of maximal heart rates. Blood samples were obtained before, immediately and 24 hours after exercise and malondialdehyde (MDA) and total sulfhydrile group (RSH) levels were measured. [Results] Both groups had similar heart rates during the test but the treadmill speed of the RA patients was significantly lower than that of the healthy volunteers. Serum MDA levels were lower than in both groups immediately after exercise, with greater decrements in the RA patients than controls. MDA levels returned to baseline 24 hours after the exercise only in the controls; they remained low in the RA patients. There was a slight increase in serum RSH levels after exercise compared to baseline in both groups. [Conclusion] Moderate intensity treadmill exercise did not have any adverse effect on the oxidant-antioxidant balance. The results suggest that such an exercise may be safely added to the rehabilitation program of RA for additional antioxidant effects. Morever, this antioxidant environment is maintained longer in RA patients.Key words: Aerobic exercise, Oxidative status, Rheumatoid arthritis