Biomarkers in airway tumors

Despite advances and improvements in diagnosis and treatment of upper aerodigestive tumors including head and neck and lung cancers, the overall survival rate of these patients remains poor. Prevention, early diagnosis, and novel therapy are under active investigation to improve the outcome of the diseases. In particular, chemopreventive strategy is a novel approach to reduce the invasive tumors by reversing the premalignant lesions with certain differentiating agents (i.e., retinoids). To conduct effective chemopreventive trials, there has been a great surge of interest in defining the biomarkers associated with the specific stages of the carcinogenesis and with intermediate end points during the therapy. Carcinogenesis in the upper aerodigestive tract has been explained by two theories, field cancerization and multistep process. The driving forces behind these processes are noted by accumulated genetic abnormalities in the entire epithelium of the airway. These genetic abnormalities include chromosome abnormalities, specific gene alterations (i.e., ras gene family, tumor suppressor genes, growth factors and their receptors), and proliferation and differentiation markers. These biomarkers are herein described in this review article.     

Evaluation of a new solution containg trehalose for twenty-hour canine lung preservation

We examined the efficacy of two new preservation solutions containing trehalose-an extracellular type (ET-K) of solution and an intracellular type (IT-K) of solution — in relation to that of Euro-Collins (EC) solution in 20-h canine lung preservation. Canine lungs were flushed with one of the three solutions (n=5 for each solution) after pretreatment with PGE₁ (20 g/kg) and were stored for 20 h at 4°C. The left lungs were transplanted and evaluated to 6 h post transplant. In the ET-K group, the arterial oxygen tension after reperfusion was significantly higher than in the IT-K and EC groups. The pulmonary vascular resistance, wet/dry weight ratio, and histological evaluation of each transplanted lung in the ET-K group were also better than in the IT-K and EC groups. This indicates that ET-K solution is useful for 20-h preservation of canine lung grafts.     

Long-term outcome in 134 patients with galactosaemia

In a retrospective study 134 galactosaemic patients, born between 1955 and 1989 in the Federal Republic of Germany were traced and their long-term outcome evaluated. We investigated 83 galactosaemic patients (78 homozygotes, 5 compound heterozygotes) by clinical, psychometric and laboratory testing; 31 patients were evaluated by medical history, the remaining 20 patients had died due to sequelae of the underlying disease. In 48 out of 78 classical galactosaemia patients galactose-free therapy had been started before the 15th day, in 19 between days 15 and 56 and in 11 patients after the 56th day. Physical findings revealed that puberty was delayed in 1 out of 18 males and 6 out of 11 females. Neurological abnormalities included ataxia (n=6), intention tremor (n=11) and microcephaly (n=10). Speech abnormalities were found in 43 out of 66 patients over 3 years of age and disturbance of visual perception and/or arithmetic deficits in 29. Intelligence declined with age, i.e., a DQ or IQ less than 85 was found in 4 out of 34 patients less than 6 years of age (12%), in 10 out of 18 between 7 and 12 years (56%) and in 20 out of 24 older than 12 years (83%). Metabolite patterns (RBC galactose-1-phosphate and UDP-galactose, plasma and urinary galactitol) did not correlate with DQ or IQ. Dietary compliance was good in almost all patients. Compound heterozygotes (n=5) had normal mental and growth development and all laboratory parameters were in the normal range. The cause of the unsatisfactory outcome of well-treated galactosaemic patients with disturbances in long-term development remains unclear. This could be due to a chronic intoxication of galactose metabolites or a deficiency of UDP-galactose or galactose-containing glycoproteins or glycolipids.This study was supported by a grant from the Stifterverband für die Deutsche Wissenschaft (Huebner-stiftung), grant TS 114/18/89 and by the Arbeitsgemeinschaft für Pädiatrische Stoffwechselstörungen     

A study on analysis of particle size distribution

Analysis of particle size distribution of a sample of fine aluminum hydroxide powder was carried out by four different methods,i. e., conductivity, air permeability, gas-adsorption and sedimentation. Each method was reproducible. The results obtained by Coulter counter and sedimentation balance were similar, and the data obtained by Lea and Nurse permeameter and Stroehlein areameter were also similar. But the results differ considerably between the former and the latter. The advantages and disavantages of each method were discussed briefly and a means of comparing the results with those obtained by surface area measurements was shown.     

Studies on corneal penetration ofp-hydroxybenzoic acid esters

Corneal permeability of variousn-alkylp-hydroxybenzoates (parabens) was studiedin vitro using excised rabbit corneas, and the effect of lipophilicity of parabens on the corneal permeability was also investigated. Permeability coefficients were obtained from the least-square linear regression after the steady state had been reached. Lipophilicity of parabens was calculated by distribution coefficients determined in octanol-S \(12_\phi [\kern-0.15em[ \) rensen’s buffer solution (pH 5.0). The relationship between lipophilicity and corneal permeability of parabens was not linear, but the optimum lipophilicity for the maximum permeation was found. The influence of tween 80 on corneal permeability of methyl and butylparaben was not significant.     

Programming a predictive rormula for angina and other risk factors in patients with cardiac diseases undergoing noncardiac operations

We programmed a formula which predicts the incidence of either myocardial infarction or cardiac death during the postoperative period. The original formula was proposed by Shah et al, based on their own data and analysis. The program is simple and is written in a language called Quick Basic. The use of this program is also simple. Such a program has improved the use of this analysis substantially. The program has been posted on to a few Computer network services as a free software.(Suwa K, Ogura S: Programming a predictive formula for angina and other risk factors in patients with cardiac diseases undergoing non-cardiac operations. J Anesth 6: 241–242, 1992)     

More than 10 years of follow-up of two patients after total femur replacement for malignant bone tumor

One patient with osteosarcoma and one with Ewing’s sarcoma of the femur were in 1987 and 1988 treated with prosthetic replacement of the femur and chemotherapy. There has been no loosening of the prostheses and no recurrence of the tumor. The patients have maintained 60% and 63% limb function scores evaluated by ISOLS criteria.

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Résumé  Deux patients, l’un avec un ostéosarcome, l’autre avec un sarcome d’EWING, furent opérés en 1987–1988 avec remplacement prothétique du fémur, associéà une chimiothérapie. Ces patients ont été suivis sans qu’il soit noté de récidive. Il n’y a pas de descellement, ni de luxation de la prothèse. Un score fonctionnel évalué selon les critères de l’ISOLS, montre une conservation de 60% et 63% de la fonction du membre inférieur.

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Accepted: 17 March 2000     

Self-assembled nanoparticles of hydrophobically-modified polysaccharide bearing vitamin H as a targeted anti-cancer drug delivery system.

Vitamin H (biotin) was incorporated into a hydrophobically modified polysaccharide, pullulan acetate (PA), in order to improve the cancer-targeting activity and internalization of self-assembled nanoparticles. The biotinylated pullulan acetate (BPA) nanoparticles were prepared by a diafiltration method and the mean diameter was approximately 100 nm. Three samples of biotinylated pullulan acetate (BPA), comprising 7 (BPA 1), 20 (BPA 2), and 39 (BPA 3) vitamin H groups per 100 anhydroglucose units of PA, were synthesized. The critical aggregation concentrations (CAC) of the BPA nanoparticles in distilled water were 3.1 x 10(-3), 4.3 x 10(-3) and 6.8 x 10(-3) mg/ml for BPA 1, BPA 2, and BPA 3, respectively. Adriamycin (ADR) was loaded into the BPA nanoparticles as a model drug. The loading efficiencies and ADR content in the BPA nanoparticles decreased with increasing vitamin H content due to a lower hydrophobicity. The RITC-labeled BPA nanoparticles exhibited very strong adsorption to the HepG2 cells, while the RITC-labeled PA nanoparticles did not show any significant interaction. The degree of the interaction increased with increasing vitamin H content. Confocal laser microscopy also revealed that internalization of the BPA nanoparticles into the cancer cells depended on the vitamin H content.