The exposure of healthy volunteers to 200 ppm 1,1,1-trichloroethane increases the concentration of proinflammatory cytokines in nasal secretions

Objectives: Irritating effects of organic solvents have usually been measured by means of questionnaires. The aim of the present study was to evaluate the sensitivity of different methods of detecting subclinical irritating effects. Methods: Twelve healthy, non-smoking students were exposed to 200 ppm and to 20 ppm 1,1,1-trichloroethane in an exposure chamber, using a crossover design. The amounts of interleukins (IL)-1β, IL-6 and IL-8 and prostaglandin E₂ (PGE₂) in nasal secretions were measured. Mucociliary transport time was determined with the saccharine test. Ciliary beat frequency of nasal epithelial cells was measured with video-interference contrast microscopy. Subjective symptoms were assessed by questionnaire. Results: Concentrations of ILs were significantly elevated after exposure to 200 ppm 1,1,1-trichloroethane (IL-1β 82.4 vs. 28.8 pg/ml (medians), P=0.003; IL-6 12.2 vs. 7.2 pg/ml, P=0.01; IL-8 549 vs. 424 pg/ml, P=0.007), whereas the other parameters remained unchanged. Conclusion: The interleukins measured proved to be sensitive indicators of irritating effects of 1,1,1-trichloroethane. The German threshold limit (MAK value) of 200 ppm 1,1,1-trichloroethane does not prevent the subclinical inflammation of nasal mucosa. Received: 3 March 1999 / Accepted: 14 June 1999     

Polyhalogenated dibenzo-p-dioxins and dibenzofurans and the immune system

We used a modified version of the popliteal lymph node assay in rats to investigate the immunosuppressive potential of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In 10 months we conducted 3 experimental series. Animals were treated with single s.c. injections of TCDD and 7 days later human red blood cells (HRBC) were injected s.c. into the right hind footpad of the rat. Another 7 days later, both popliteal lymph nodes were prepared, weighed, the cell number was counted and the quotients (index) of these variables from the treated and the untreated side were determined. The doses applied in three experimental series were 600, 60, 6, 0.6, and 0.06 ng TCDD/kg body wt. In the first experimental series only the three highest doses were tested, in a second experimental series doses of 60, 6, 0.6, 0.06 ng TCDD/kg body wt were applied. Combining the results of these two experimental series, a statistically significant difference was found in the cell number index between the controls and the two highest doses tested (60 and 600 ng/kg body wt;p <0.01). This result was recently published as an abstract (Korte et al. 1990). However, with slight methodological changes in the third series of experiments (doses applied: 600, 60, 6, 0.6, and 0.06 ng TCDD/kg body wt) and using a greater number of animals we could not confirm these preliminary results. No difference was seen in the immune response to the antigen challenge in controls and in any of the treatment groups. We conclude that TCDD does not clearly influence the immune response as observed in the popliteal lymph node assay under our experimental conditions.     

Systemic chemotherapy

The main use of systemic chemotherapy in metastatic melanoma remains palliative. Dacarbazine (dimethyl-1-triazeno imidazole-4-carboxamide [DTIC]) is the standard chemotherapy agent for advanced disease. The combination chemotherapy and biochemotherapy regimens have achieved higher response rates, but have not led to durable remission or improved survival. The field of systemic therapy remains in need of a more effective and less toxic treatment strategy.     

P21WAF1, P27KIP1, TP53 and C-MYC analysis in 204 ovarian carcinomas treated with platinum-based regimens.

BACKGROUND: The prognostic and predictive value of cell cycle regulatory proteins in ovarian cancer has not been established. We evaluated the clinical and biological significance of P21(WAF1), P27(KIP1), C-MYC, TP53 and Ki67 expressions in ovarian cancer patients. MATERIALS AND METHODS: Immunohistochemical analysis was performed on 204 ovarian carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IV treated with platinum-based chemotherapy. Multivariate analysis with Cox and logistic regression models was performed in the whole group, and in the TP53-negative and TP53-positive subgroups. RESULTS: High P21(WAF1) labeling index (LI) was an independent positive predictor of platinum-sensitive response (P = 0.02). Overall survival was positively influenced by P21(WAF1) LI (P = 0.02) or by P21(WAF1) plus P27(KIP1) LI (P = 0.004) in the TP53-negative group only. Ki67 LI showed borderline association with disease-free survival (P = 0.05). Growth fraction was negatively associated with P21(WAF1) and P27(KIP1) indices in the TP53-negative group (P = 0.023 and 0.008, respectively), and these associations were borderline or lost in the TP53-positive group. Endometrioid and clear cell carcinomas differed from other carcinomas by having a low incidence of TP53 accumulation, a high incidence of C-MYC overexpression (70%) and a low median Ki67 LI (all with P <0.001). CONCLUSIONS: We have shown an independent predictive value of P21(WAF1) LI in ovarian carcinoma patients. The prognostic value of P21(WAF1) and P21(WAF1) plus P27(KIP1) LI was determined by TP53 status. A high frequency of C-MYC overexpression in endometrioid and clear cell carcinomas may suggest its role in the development of these tumor types.     

Clinical validation of a new olfactory test

A new approach to clinical olfactometry is presented using nasal sprays. A special dosage valve was used to standardize an aerosol size to 40 μm. For evaluation a 6 × 6 matrix (substance/olfactory quality) with verbal associative clues was used according to test psychological findings. Validation took place in three steps after determining smell-associated thresholds in preliminary examinations. Recognition of different aromas administered either by spraying into the open mouth from a distance of 5 cm using nasal sprays or sniffing opened bottles was compared in 50 subjectively normosmic subjects. Findings showed that the correspondence between the two procedures was relatively high, with global identification of odorous substances as high as 98.4% in the spray test. The number of substances used was next reduced to those six substances providing the most reproducible results in an investigation with 56 normosmic and 55 hyposmic subjects. Verbal associative clues were also tested. In a last step 50 patients with hyposmia of various origin and 110 normosmic subjects were tested, allowing previous results to be reproduced regardless of the cause of hyposmia. The spray test was shown to be easily performed and was suitable as a screening test, with a sensitivity of 88% and a specificity of 100%. Received: 29 September 1997 / Accepted: 11 February 1998     

Comparison of the radiosensitivity of normal-tissue cells with normal-tissue reactions after radiotherapy

PURPOSE: To investigate whether the in vitro radiosensitivity of normal lymphocytes and fibroblasts evaluated by the micronucleus (MN) assay predicts acute and late reactions after radio-therapy in cancer patients. MATERIALS AND METHODS: Studies were performed on blood samples from 31 cervical and head and neck cancer patients and on skin fibroblasts from eight of the cancer patients. The radiosensitivity of lymphocytes and of fibroblasts was also assessed in 24 and five healthy donors, respectively. Radiosensitivity was measured after in vitro irradiation with doses ranging from 2 to 5 Gy using micronucleus frequency (the number of micronuclei per single binucleated (BN) cell) and the percentage of BN cells with micronuclei. The in vitro results were compared with the maximum grade of acute and late reactions. RESULTS: There was no significant difference in cellular radiosensitivity between cancer patients and healthy donors. Although cancer patients differed considerably in normal-cell radiosensitivity, no correlation was found between radiosensitivity, either of lymphocytes or fibroblasts, and acute and late clinically observed side effects. In addition, no relationship was observed between the radiosensitivity of lymphocytes and fibroblasts derived from the same donors. CONCLUSION: The data do not support the usefulness of the MN assay in predicting normal-tissue response to radiotherapy in cancer patients.     

Isoametropic amblyopia due to high hyperopia in children.

PURPOSE: To identify children with isoametropic amblyopia due to moderate to high hyperopia and evaluate associated findings and visual acuity outcome. METHODS: Charts from two university's pediatric ophthalmology clinics were reviewed retrospectively. Healthy children with > or = +4.5 D spherical equivalent who did not have anisometropia > or = 1.5 D were selected for data collection. The charts of qualifying children with bilateral amblyopia (visual acuity of 20/40 or less) were further analyzed. RESULTS: Identified were 418 children with the above set of criteria for hyperopia; 36 of these children had isoametropic amblyopia (bilateral amblyopia). This gives an estimated prevalence of isoametropic amblyopia of 8.6% in children with at least 4.5 D of hyperopia in one or both eyes. The children with isoametropic amblyopia presented at a later age (5 years, 1 month) than the overall group of hyperopes (3 years, 5 months). Strabismus was less prevalent in this group (64%) than in the entire population of children with high hyperopia (81%). These children's amblyopia responded well to treatment with glasses, and patching in 13 (36%) cases. Surgical intervention for residual strabismus was necessary in very few cases (2 of 36, 5.5%). CONCLUSION: Children with hyperopia > or = 4.5 D have an increased risk of amblyopia and strabismus that further threatens their future visual function. Isoametropic amblyopia is a real risk in these children. Based on these results, hyperopic correction should be prescribed for children with > or = 4.5 D of hyperopia even if no strabismus or fixation preference is detected, to reduce this risk. Screening programs should also be in place to identify these children at an early age.     

Maspin expression is characteristic for cisplatin-sensitive ovarian cancer cells and for ovarian cancer cases of longer survival rates.

High cytoplasmic expression of maspin was described in ovarian cancers of shorter survival rates. Until now, no relationship has been described between expression of maspin and sensitivity to cisplatin in ovarian cancers. This study aimed at examining the relationship between expression of maspin, detected by immunohistochemistry and clinical response to cisplatin in ovarian cancer cases as well as the in vitro sensitivity to cisplatin of 11 ovarian cancer cell lines. The analyzes were performed on 73 samples of ovarian cancer and on A2780P, A2780RCIS, CAOV-3, EFO 21, EFO 27, ES-2, Mdah 2774, OAW 42, OVCAR-3, PA-1, and SKOV-3 ovarian cancer cells. Cytoplasmic maspin expression in studied cells significantly correlated with cisplatin sensitivity. A significantly shorter overall survival and progression-free survival was associated with lower cytoplasmic maspin expression at first-look laparotomies and nuclear maspin expression and secondary cytoreductions. Higher nuclear maspin at first-look laparotomies expression was specific for cases of complete response. In the study, the elevated expression of maspin was shown to be typical for cisplatin-sensitive ovarian cancers.     

The effective dose (Deff) for electron beams.

BACKGROUND AND PURPOSE: Calculation of the effective dose and proposal of a dose specification method for the electron beams. PATIENTS AND METHODS: In a homogenous water phantom the 3D dose distributions for electron beams of energy 6, 9, 12, 15, 18 and 21 MeV and beam size 10x10 cm were calculated. For a volume encompassed with 80, 85 and 90% isodose, the mean dose and the SD were calculated for each energy. Using the Brahme's formulae, the effective dose was calculated. RESULTS: The larger the minimum dose (value of the encompassing isodose), the larger the mean dose and the smaller the SD. The mean doses and SD to the volume encompassed with 80, 85 and 90% are in the range of 91-94%, and 5.1-6.2%, 93-96% and 4.2-4.6%, 94-96% and 3.0-3.2%, respectively. Thus the effective dose for the volume encompassed with 80, 85 and 90% are about 90, 93 and 95%, respectively. CONCLUSION: Taking into account the requirements regarding dose uniformity within the PTV and the sparing effect for normal tissue situated under the PTV, we propose to keep the 85% isodose as a minimum one and to prescribe the dose to the 90% isodose. The present method may be applied for single electron beams and typical cases.