Carboplatin-radiation interaction in squamous cell carcinoma cell lines.

Chemoradiotherapy has been considered one of the most promising improvements in the treatment of advanced head and neck cancer. This article describes in vitro chemosensitivity to carboplatin in five squamous cell carcinoma cell lines established from head and neck cancers and in one vulvar squamous cell carcinoma cell line. Sensitivity to carboplatin was found to vary markedly when using the 96-well plate clonogenic assay and continuous drug exposure. The difference in carboplatin response between the most sensitive and the most resistant cell lines was fourfold. No cross-resistance was observed between inherent radiosensitivity and chemosensitivity. Effects of concomitant use of carboplatin and radiation were further investigated in the two cell lines that were found to be most sensitive to carboplatin. The drug was administered 1 hour before acute radiation doses, and an additive effect was observed in both cell lines.     

Human papillomavirus testing with the hybrid capture 2 assay and PCR as screening tools

The recognition of high-risk human papillomaviruses (HPVs) as etiological agents of cervical cancer has increased the demands to use testing for HPV for the detection of abnormal cervical smears and for cervical cancer screening. The present study compared the performance of the Hybrid Capture 2 (HC2) assay with that of PCR for the detection of significant cervical lesions in 1,511 women with different risks for HPV infections in three New Independent States of the former Soviet Union. The results showed that the level of agreement between the HC2 assay and PCR was substantial, with a kappa (Cohen) value of 0.669 (95% confidence interval [CI], 0.629 to 0.709). Of the 228 samples with discrepant results, 92 were positive by the HC2 assay but negative by PCR, whereas 136 samples were PCR positive but HC2 assay negative. The positive predictive values (PPVs) of the HC2 assay and PCR in detecting high-grade intraepithelial lesions (HSILs) were 4.5% (95% CI, 3.5 to 5.5%) and 3.6% (95% CI, 2.7 to 4.5%), respectively, and the negative predictive values (NPVs) were 99.6% (95% CI, 99.3 to 99.9%) and 99.3% (95% CI, 98.9 to 99.7%), respectively. The sensitivities of the HC2 assay and PCR for the detection of HSILs were 85.2 and 74.0%, respectively, and the specificities were 67.2 and 64.1%, respectively. In receiver operating characteristic (ROC) analysis, the performance of the HC2 assay for the detection of HSILs was excellent (P = 0.0001); the area under the ROC analysis curve was 0.858 (95% CI, 0.811 to 0.905), and the optimal balance between sensitivity (86.5%) and specificity (80%) was obtained with an HC2 assay cutoff level of 15.6 relative light units/positive control. Use of this cutoff would increase the specificity of the HC2 assay to 80.0% without compromising sensitivity. In conclusion, the results of PCR and the HC2 assay were concordant for 85% of samples, resulting in substantial reproducibility. Both tests had low PPVs, equal specificities, and equal (almost 100%) NPVs for the detection of HSILs; but the sensitivity of the HC2 assay was slightly better.     

Absence of glutamic acid decarboxylase antibodies in childhood epilepsies

Glutamic acid decarboxylase antibodies are present in some patients with therapy-resistant epilepsy. The authors measured glutamic acid decarboxylase antibodies in an unselected population of 114 children with different types of epilepsy. Three children with temporal lobe epilepsy and six children with various other types of epilepsy had intractable epilepsy. None of the children tested positive for glutamic acid decarboxylase antibodies. The study suggests that glutamic acid decarboxylase antibody testing cannot be recommended in unselected cases of childhood epilepsy.     

Stability of autoantibodies and their relation to genetic and metabolic markers of Type I diabetes in initially unaffected schoolchildren

Aims/hypothesis. To study temporal changes in positivity for autoantibodies associated with Type I (insulin-dependent) diabetes mellitus and the relations between these antibodies, HLA-DQB1-risk markers and first-phase insulin response (FPIR) in non-diabetic schoolchildren.¶Methods. The stability of the antibody status over 2 years was assessed in 104 schoolchildren initially positive for islet cell antibodies (ICA) or antibodies to the 65 000 M_r isoform of the glutamic acid decarboxylase (GADA) or both and in 104 antibody-negative control children matched for sex, age and place of residence. All children were also studied for their first-phase insulin response and HLA-DQB1 alleles on the second occasion.¶Results. On the second occasion 3 of the 98 initially ICA-positive children, 3/13 of those positive for antibodies to the IA-2 protein (IA-2A), 1/17 GADA-positive and 2/7 of those positive for insulin autoantibodies (IAA) tested negative for these antibodies. Children with IA-2A, GADA, IAA and multiple ( ≥ 2) antibodies had significantly lower first-phase insulin responses than the control children. In contrast, these responses did not differ between subjects with and without specific HLA-DQB1-risk alleles or genotypes. Of the six subjects with a considerably reduced first-phase insulin response three had multiple antibodies on both occasions but none of them had a DQB1 genotype conferring increased diabetes risk. Two subjects progressed to Type I diabetes within 3.4 years of follow-up, both of them having multiple antibodies and a considerably reduced first-phase insulin response but neither of them having a DQB1-risk genotype.¶Conclusions/interpretation. Positivity for diabetes-associated autoantibodies is a relatively stable phenomenon in unaffected schoolchildren, although conversion to seronegativity can occur occasionally. Our observations also indicate that DQB1 alleles associated with decreased susceptibility to Type I diabetes do not protect from impaired beta-cell function or from progression to overt disease in initially unaffected schoolchildren. [Diabetologia (2000) 43: 457–464]     

Lowered vision as a risk factor for injurious accidents in older people

BACKGROUND AND AIMS: Poor vision in older people is often related to increased fall risk. However, the association of the severity between visual deficit and risk for all kind of injurious accidents has not been widely studied. The aim of this study was to examine whether visual loss is associated with higher incidence of injurious accidents and whether walking speed or physical activity play a mediating role in the association. METHODS: 416 persons aged 75 and 80 years at baseline underwent visual acuity measurements. Visual acuity (VA) <0.3 in the better eye, with spectacle correction when necessary, was defined as visual impairment, VA >or=0.3 but 0.5 as normal VA. Hospital records of accidents resulting in injury were monitored for 10 years after baseline. RESULTS: During the 10-year follow-up, 239 (58%) participants suffered at least one injurious accident. The risk for injurious accidents in a multivariate model adjusted for age, gender, eye-related diseases, diabetes and cardiovascular diseases among participants with lowered vision was 1.45 (95% CI 1.08- 1.94), compared with that for people with normal visual acuity. Participants with visual impairment did not have an increased risk for injurious accidents (HR 1.20, 95% CI 0.82-1.75). Furthermore, neither walking speed nor physical activity had a mediating effect on the relationship between visual loss and accidents. CONCLUSIONS: Lowered vision is a risk factor for injurious accidents in older people independent of mobility and physical activity. Interestingly, more severe visual impairment did not increase the risk. Early intervention strategies, for example, proper correction of refractive errors or cataract extraction, may potentially prevent injurious accidents in older people.