Transplantability of human head and neck squamous cell carcinomas in athymic nude mice

Tumor material from 91 patients with squamous cell carcinoma of the head and neck was transplanted subcutaneously in athymic nude mice. In the first (man to mouse) passage, the calculated mean probability of tumor take in a single mouse was 11%. The probability of growth in the first passage was significantly better for moderately and poorly differentiated tumors than for well-differentiated tumors. Also, the implantation of lymph node material resulted in a significantly better tumor take rate than material taken from a primary tumor. Transplantability was not dependent on the following characteristics: localization, T or N stage of the tumor, or the sex of the patients. Once growth was established, all variables studied had no influence on the probability of growth in the subsequent mouse passages. A relationship between tumor growth in nude mice and patient prognosis could not be found. When transplanting head and neck squamous cell carcinoma in nude mice, it has to be recognized that some tumor characteristics will influence the success of tumor growth.     

Usher syndrome: clinical findings and gene localization studies

The issue of genetic heterogeneity is a critical problem in the localization of the gene(s) for Usher syndrome. Based on the data obtained on families studied to date, the differences between type I and type II Usher syndrome appear quite distinct with regard to auditory and vestibular function. Although the majority of families can be confidently diagnosed as typical type I or type II, clinical investigations revealed four families with findings that did not fit into either of the two more common subtypes. These findings emphasize the critical importance of an in-depth clinical analysis concomitant with the linkage investigation to assure accurate subtyping of Usher syndrome. Based on an analysis of only those families with definite type I or type II Usher syndrome, approximately 17% of the genome can be excluded as a potential site of the gene for type I, and 14% can be excluded as the site for the type II gene. This study will continue until the Usher gene(s) is successfully localized.     

Arterial and venous effects of serotonin in the forearm of healthy subjects are not age-related

The influence of age on the regional arterial and venous effects of serotonin (5-HT) was investigated in 13 young (aged 22-31 years) and seven older (aged 50-69 years) healthy volunteers. Single-dose infusions of 5-HT (1, 10, and 80 ng/kg/min) and of the 5-HT2 receptor antagonist ritanserin (50, 150, and 500 ng/kg/min) were administered into the brachial artery. Subsequently, the relative arterial and venous effects of the highest dose of 5-HT were investigated. Forearm blood flow (FBF) and maximum venous outflow (MVO) were measured by venous occlusion plethysmography. Heart rate (HR) and intraarterial (i.a.) blood pressure were recorded semicontinuously. In both age groups, 5-HT induced an initial transient arterial dilation, followed by a persistent increase in FBF for the doses of 1 and 10 ng/kg/min and a relative small decrease in FBF for the highest dose. In both age groups, the highest dose of 5-HT induced a similar large reduction in MVO (p less than 0.05 for both). The reduction in MVO was attenuated by ritanserin (500 ng/kg/min, p less than 0.05 for both groups). In the younger subjects, this dose of ritanserin also unmasked an arterial dilator effect of the highest dose of 5-HT (p less than 0.05). The single infusions of ritanserin did not influence FBF significantly in either study group. No significant differences were observed between the age groups. These results show that in the forearm of healthy subjects arterial and venous vascular responses to 5-HT were not age-related. In the arterial vascular bed, 5-HT acted predominantly as a vasodilator; at high doses, mainly venous vasoconstriction was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rhinitis Symptom Utility Index (RSUI) in Chinese Subjects: A Multiattribute Patient-preference Approach

Background: The Rhinitis Symptom Utility Index (RSUI), originally developed in the United States, consists of a patient-preference weighting scheme and a 10-item questionnaire measuring the severity and frequency of rhinitis related symptoms over a 14-day period. This study aimed to determine whether the Chinese RSUI could adopt the US-based multi-attribute utility function (MAUF) in scoring rhinitis symptoms. Methods: In a Hong Kong study, 116 Chinese adults with allergic rhinitis completed the RSUI questionnaire and 36-item Short-Form Health Survey (SF-36) after they had been seen by two otorhinolaryngologists for disease-severity ratings. Respondents then completed computer-administered direct preference measures, i.e., visual analogue scale (VAS) and standard gamble (SG) assessments. The VAS and SG data were used to estimate a MAUF for the Chinese-based RSUI. Results: The derived MAUF was somewhat different than the one developed for the US RSUI. Test–retest reliability for the Chinese RSUI was satisfactory (ICC = 0.71, p<0.001). Scores differentiated among cases with mild, moderate, and severe symptoms (p<0.001); and between those who did and did not require medications to control symptoms (p = 0.031). Findings were significantly correlated with SF-36 domain scores (r = 0.19 to 0.37; p=0.041 to <0.001). When the US-based scoring function was applied to the Chinese subjects, the resulting mean RSUI score was significantly lower (p<0.001). Comparisons between directly measured VAS and SG scores between the US and Chinese samples, demonstrated significant differences (all p<0.05), with the US subjects consistently rating rhinitis symptoms as worse than Chinese subjects. Conclusions: The Chinese RSUI has good measurement properties that reflect patient preferences from the Chinese. Results suggest that there are differences in preference rating between US and Chinese subjects and that use of the US-based preference function for the RSUI would bias the measurement of rhinitis symptom outcomes in Chinese subjects.     

Rational design of hypoallergens applied to the major cat allergen Fel d 1

BACKGROUND: Allergen-specific immunotherapy is the only treatment for allergic disease providing long-lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy. OBJECTIVE: The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen. METHODS: The three-dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition-ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay. RESULTS: Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400-900 times lower IgE-binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1. CONCLUSION: By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE-binding capacities and retained T cell reactivities. This strategy may be applied to any well-characterized allergen to improve immunotherapy for allergic patients.     

Evidence that dopamine in the nucleus accumbens is involved in the ability of rats to switch to cue-directed behaviours.

Recently we have reported that injections of d-amphetamine into the nucleus accumbens enhanced the number of switches to cue-directed behaviours without an effect on the number of switches to non-cue-directed behaviours in a swimming test. In the present study we investigated to what extent this effect is mediated via the dopaminergic system in the nucleus accumbens. For that purpose drugs selective for D1- and D2-receptors were studied in this swimming test. It was found that the selective D2-agonist LY 171 555 (50 ng/0.5 microliters) enhanced the number of different cue-directed behaviours. The selective D2-antagonist raclopride (50 ng/0.5 microliters) decreased it. Furthermore an ineffective dose of raclopride attenuated the effect of LY 171 555. Both the selective D1-antagonist SCH 23390 (400 ng/0.5 microliters) and the selective D1-agonist SKF 38393 (50-400 ng/0.5 microliters) decreased the number of different cue-directed behaviours. The effect induced by SCH 23390 could not be blocked by SKF 38393. Similarly the effect induced by SKF could not be attenuated by SCH 23390. These data point to a role for dopamine D2-receptors in the ability to switch to cue-directed behaviours. The present findings do not yet allow the conclusion that D1-receptors are involved.     

Targeted routine asthma care in general practice using telephone triage

BACKGROUND: There is a high non-attendance rate for traditional clinic-based routine asthma care in general practice. Alternative methods of providing routine asthma care need to be examined. AIM: To examine the cost and effectiveness of targeted routine asthma care in general practice using telephone triage, compared to usual clinic care. DESIGN OF STUDY: An open randomised controlled trial. SETTING: A single semi-rural practice in the southwest of England. METHOD: Adult patients with asthma were randomised to receive either their routine asthma care in the surgery or care by telephone triage. Asthma control parameters, health status and NHS resource utilisation were measured over the 12-month study period. RESULTS: One hundred and ninety-four patients were randomised and 35% per cent more patients (n = 84 versus n = 62) received more than one consultation in the telephone group. Asthma control as measured by the asthma control questionnaire (ACQ) was similar in the clinic and telephone groups: mean change in ACQ = -0.11 (95% CI = -0.32 to 0.11) versus -0.18 (95% CI = -0.38 to 0.02). Mean NHS costs were 210 pounds sterling per patient per year in the telephone group compared to 334 pounds sterling in the clinic group (P-value of bootstrapped difference = 0.071). CONCLUSION: Targeted routine asthma care by telephone triage of adult asthmatics can lead to more asthma patients being reviewed, at less cost per patient and without loss of asthma control compared to usual routine care in the surgery.     

Probing insulin's secondary structure after entrapment into alginate/chitosan nanoparticles.

The aim of the present study was to probe the structural integrity of insulin after being entrapped into chitosan/alginate nanoparticles produced by ionotropic polyelectrolyte pre-gelation. By manipulating the alginate:chitosan mass ratio and the pH during nanoparticle production, desired nanoparticles with a mean size of 850 (+/-88)nm and insulin association efficiency of 81 (+/-2)% were obtained. Insulin secondary structure was assessed by Fourier transform infrared (FTIR) and circular dichroism (CD) after entrapment into nanoparticles and after release from the particles under gastrointestinal simulated conditions. FTIR second-derivative spectra and area-overlap compared to an insulin standard confirmed that no significant conformational changes of insulin occurred in terms of alpha-helix and beta-sheet content. Far-UV-CD spectra corroborated the preservation of insulin structure during the nanoparticle production procedure. The presented nanoparticulate system is a promising carrier for insulin oral delivery since it preserves insulin structure and therefore also, potentially, its bioactivity.