Clinical evaluation of biomarkers in Gaucher disease

Novel or candidate biomarkers require thorough evaluation to establish their utility in a clinical setting. This paper describes an evaluation of several established enzyme markers of Gaucher disease and a newly-described chemokine, pulmonary and activation-regulated chemokine (PARC). The ability of the biomarkers to rank patients with Gaucher disease in order of disease severity and organ bulk, and to reflect changes in key clinical parameters in response to enzyme replacement therapy were evaluated. PARC concentrations were found to be reliably correlated with visceral disease and with key clinical responses to enzyme replacement in an unbiased manner. Unlike chitotriosidase and serum angiotensin-converting enzyme activity, genetic variation in serum PARC did not appear to influence its utility as a biomarker.
Conclusion: For each new candidate biomarker of lysosomal storage diseases, a similar clinical evaluation will be required, though the approach will need to be modified according to the clinical features and natural history of each disorder.     

Ce(SO4)2对玉米根尖细胞遗传毒性和细胞毒性的研究

[目的]研究Ce(SO4)2对玉米根尖细胞的遗传毒性和细胞毒性。[方法]用不同梯度浓度的Ce(SO4)2对玉米根尖细胞进行染毒处理，检测玉米根尖细胞的微核率和有丝分裂指数。[结果]当Ce(SO4)2≥10mg/L时，玉米根尖细胞的微核率显著上升，当Ce(SO4)2达到1000mg／L时，玉米根尖细胞的有丝分裂指数显著下降。[结论]提示一定浓度的Ce(SO4)2对玉米根尖细胞具有一定的遗传毒性和细胞毒性。     

实体瘤手术前后嗜酸粒细胞观察：（附42例临床报告）

肿瘤常伴有血中嗜酸粒细胞增高,称肿瘤相关性周围血嗜酸粒细胞增多(TABE)。本文对42例实体瘤患者进行了周围血嗜酸粒细胞统计,39例有TABE,其中尤以恶性肿瘤较为显著。无论恶性或良性肿瘤手术后计数,嗜酸粒细胞均恢复正常水平,提示嗜酸粒细胞测定可为临床实体瘤治疗转归起参考作用。     

Antibodies to diphtheria, tetanus and pertussis in infants before and after immunization with DTP (Triple Antigen) vaccine

Objective : To determine antibody levels to the Australian manufactured combined diphtheria, tetanus and pertussis (DTP) vaccine (Triple Antigen, CSL Ltd) in infante before and after their primary immunization course.
Methodology : Serosurvey (antibody prevalence study) in two groups: infants aged 5-9 weeks who had not received any immunizations ( n = 25), and infants aged 7-10 months who had received two ( n = 25) or three immunizations ( n = 57) with DTP, sampled from infants attending the Royal Children's Hospital, Melbourne, either as inpatients or outpatients between February and April 1993. The immunization history for each infant was determined from hospital records, the parent-held child health record, or the local council or family doctor who immunized the infant.
Results : Enzyme immunoassay (EIA) of antibodies to diphtheria and tetanus showed all infants to have adequate protective levels after two or three vaccinations (£0.01 IU/mL). All subjects who had received all three DTP vaccinations had detectable antibody to at least one pertussis antigen. Antibodies to the pertussis antigens filamentous haemagglutinin and pertussigen (pertussis toxin) were comparable to levels determined for whole cell pertussis vaccines used elsewhere in the world. EIA-determined antibodies to pertussis agglutinogen type 2 and agglutinogen type 3 showed substantially higher geometric mean titres when results for pre-immunization and post-immunization subjects were compared.
Conclusions : These data show that the Australian manufactured DTP vaccine has immunogenic properties similar to those of vaccines used elsewhere, and that antibody concentrations following immunization are at levels consistent with efficacy.     

Child Behaviour Checklist classification of behaviour disorder

Objective : The aim of this study was to determine the applicability of the published clinical cut-off scores of the Child Behaviour Checklist (CBCL) for the classification of behaviour disorders.
Methodology : Child Behaviour Checklists were obtained for 1342 subjects newly referred to the six major mental health centres in Melbourne. The normative community sample of 1002 7-, 12- and 15-year-olds was drawn from a school-based asthma prevalence study.
Results : The mean total problem T-score for the children referred to mental health centres was 67 and was above the clinical range for all age groups. Using referral to psychiatric services as the gold standard, the sensitivity and specificity of the CBCL using a cut-off of ≥ 60, was 77.4 and 83.2%, respectively. This compares favourably with the sensitivity of 68% and specificity of 82% for the American sample. Using a cut-off score of ≥ 63, the sensitivity was 70.5% and the specificity was 88.6%. The referred and community samples differed with respect to socio-economic status, family structure and mothers' level of education. Fifty-two per cent of the clinically referred children lived with both parents, compared with 89% of the community sample.
Conclusions : While there are some limitations to this study in terms of both the clinic and community sample, support is provided for the usefulness and applicability of the recommended CBCL cut-off scores in an Australian population.     

Dose response of human tumor cells to rhodamine 123 and laser phototherapy

Previous studies have shown that Rhodamine 123 (Rh123) is an efficient tumor targeting agent for argon laser photodynamic therapy in vitro. Effectiveness of this approach for cancer treatment in vivo will depend on Rh123 tumor uptake kinetics and laser energy delivery via fiberoptics to the tumor site. In the present study, tumor and normal cells were exposed in vitro to 1 μg/mL Rh123 until 10%, 50%, and 100% of maximum uptake was achieved. Laser treatment response was monitored by trypan blue exclusion for tumor cell viability and by MTT tetrazolium assays to measure mitochondrial dehydrogenase activity. TE671 fibrosarcoma cells were highly sensitive to argon laser phototherapy (514 nm, 5 W, 1 minute, Tmax = 8°C), with mitochondrial inhibition seen after Rh123 uptake of 12, 50, and 100 ng/million cells. P3 squamous cell carcinoma cells were inhibited 20% and 75% by the laser after Rh123 uptake of 13 or 30 ng/million cells, respectively. M26 melanoma cells were not sensitive to the laser after 15 ng/million cells Rh123 uptake but were inhibited 45% and 75% after Rh123 uptake of 80 and 160 ng/million cells. Micro2 fibroblast mitochondrial activity was reduced less than 25% by the laser after Rh123 uptake of 50 ng/million cells. Cell viability after maximum Rh123 uptake and laser treatment was decreased to 30%, 15%, and 2% for M26 melanoma, P3 squamous cell carcinoma, and TE671 fibrosarcoma cells, but remained over 80% for Micro2 fibroblasts. The results suggest that Rh123 laser treatment response depends on tumor type and drug uptake level, with normal cells being much less sensitive to phototherapy.     

Life Stage,Alcohol Consumption Patterns,Alcohol-Related Consequences,and Gender

This paper presents findings from a European collaborative study. A common framework for reanalysis of existing data was devised. Alcohol-related problems encountered were classified as internal and external. Logistic regression analyses were then conducted to predict lifetime presence of any internal problem, any external problem, and any problem at all. The predictor variables were gender, life stage (corresponding roughly to young, middle and older age), past year's drinking level in four categories of grams of alcohol per month, and past year's binge drinking. All four predictor variables were associated with the presence of alcohol-related problems, with women and retired people having fewer problems and heavy drinkers and binge drinkers having more. At all levels of alcohol consumption, men were more likely than women to experience at least one adverse consequence. Internal problems were more common than external problems. Country differences are discussed and recommendations are made for further studies.