An evaluation of procedures used in staging carcinoma of the cervix

A review of 227 cases of invasive carcinoma of the cervix was undertaken to determine the efficacy of procedures using in the staging of this disease. All patients had a pretreatment chest radiography and intravenous pyelogram. 96.5% had pretreatment cystoscopy, 98.6% had pretreatment proctoscopy, and 92% had a pretreatment barium enema. These patients were retrospectively staged on the findings of physical examination only. Each additional procedure was then evaluated by comparison with the initial staging. Cystoscopy and chest film findings each would have changed the clinical stage in fewer than 1% of cases, barium enema in 1.4%, and proctoscopy in 2.2%. No patient had a positive barium enema without a positive proctoscopy, while two patients had positive proctoscopies with negative barium enemas. The overall yield of positive findings by pretreatment intravenous pyelography was 7.3%. Lymphangiography, although inconsistently done, yielded positive findings in all stages. Chest radiographs, intravenous pyelography, proctoscopy, and lymphangiography are recommended as part of the pretreatment workup of patients with carcinoma of the cervix. Routine barium enema is no longer recommended, and cystoscopy is only recommended in patients with clinical stage IIB disease or greater.     

A new quinoline-carbamate aphicide

We found that it was nearly impossible to apply the quinoline-carbamate aphicide per os by means of synthetic diets, owing to its high feeding-deterrent-effect. After application via the roots of the host plant, this systemic compound is deposited on the leaf surface. The results suggest that the toxic effect is not the result of the oral uptake of phloem sap, but of the tarsal contact with the toxicant. Sensitivity of aphids to this compound and LD50-values were determined after topical applications.     

Tetrahydroisoquinolinecarboxylic acids and catecholamine metabolism in adrenal medulla explants

In a study of the relationship of the tetrahydroisoquinolinecarboxylic acids (TIQCAs) to catecholamine metabolism, we have investigated their effects on cultured rat adrenal medulla explants. Medullae were incubated in medium containing norlaudanosolinecarboxylic acid (NLCA) or 3',4'-deoxynorlaudanosolinecarboxylic acid (DNLCA) (0.5 mM) in the presence and absence of [3H]tyrosine. By paired-ion reverse-phase high pressure liquid chromatography, tissue epinephrine (EPI), norepinephrine (NE), dopamine (DA) and TIQCA were resolved. Endogenous concentrations were measured with electrochemical detection, and radioactivity was assayed by collecting appropriate effluents. Tissue levels of the TIQCAs reached saturating levels of 0.36 mM by about 20 hr. DNLCA elicited a significant decrease (60%) in endogenous DA, NE and EPI at 40 hr, whereas only DA was depressed at 30 hr. NLCA had little effect after 30 or 40 hr. When tissues were maintained in the presence of alpha-methyltyrosine (0.5 mM) for 40 hr, catecholamine levels were depressed to an extent similar to that observed with DNLCA. Incubation with [3H]tyrosine in the presence of TIQCAs revealed inhibition of tyrosine uptake and suggested a reduction in the rate of catecholamine synthesis. These results are consistent with previous data on the inhibition of tyrosine 3-monooxygenase by DNLCA in vitro.     

Dissociation between the potency and reversibility of the insulinotropic action of two meglitinide analogues

The non-sulphonylurea hypoglycaemic agent repaglinide is about one order of magnitude less potent, in terms of insulinotropic efficiency, than S3075, another meglitinide analogue. In the present study, the effects of these two drugs upon 86Rb outflow, 45Ca efflux and insulin release from prelabelled rat pancreatic islets were investigated in a perifusion system. At a concentration of 10 microM, which is sufficient to evoke a maximal secretory response in incubated islets, both agents inhibited 86Rb efflux from islets perifused in the absence of D-glucose, and stimulated both 45Ca efflux and insulin release from islets perifused in the presence of 6 mM D-glucose. The stimulation of 45Ca efflux from prelabelled islets was suppressed in the absence of extracellular Ca2+. The cationic and secretory response to repaglinide differed, however, from that evoked by S3075, in persisting for at least 20 min after removal of the drug from the perifusion medium, whilst the changes in 86Rb outflow, 45Ca efflux and insulin release caused by S3075 were rapidly reversible. These findings indicate that there is no parallel between the insulinotropic efficiency of distinct meglitinide analogues, and the reversibility of their functional effects. Since a comparable dissociation was recently documented in the case of hypoglycaemic sulphonylureas, the present observations reinforce the view that distinct molecular determinants may rule the relative insulinotropic potency of sulphonylureas and structurally related meglitinide analogues, on one hand, and the reversibility of their biological action, on the other hand.     

The CTFA Evaluation of Alternatives Program: an evaluation of in vitro alternatives to the Draize primary eye irritation test. (Phase III) surfactant-based formulations

The CTFA Evaluation of Alternatives Program is an evaluation of the relationship between data from the Draize primary eye irritation test and comparable data from a selection of promising in vitro eye irritation tests. In Phase III, data from the Draize test and 41 in vitro endpoints on 25 representative surfactant-based personal care formulations were compared. As in Phase I and Phase II, regression modelling of the relationship between maximum average Draize score (MAS) and in vitro endpoint was the primary approach adopted for evaluating in vitro assay performance. The degree of confidence in prediction of MAS for a given in vitro endpoint is quantified in terms of the relative widths of prediction intervals constructed about the fitted regression curve. Prediction intervals reflect not only the error attributed to the model but also the material-specific components of variation in both the Draize and the in vitro assays. Among the in vitro assays selected for regression modeling in Phase III, the relationship between MAS and in vitro score was relatively well defined. The prediction bounds on MAS were most narrow for materials at the lower or upper end of the effective irritation range (MAS = 0-45), where variability in MAS was smallest. This, the confidence with which the MAS of surfactant-based formulations is predicted is greatest when MAS approaches zero or when MAS approaches 45 (no comment is made on prediction of MAS > 45 since extrapolation beyond the range of observed data is not possible). No single in vitro endpoint was found to exhibit relative superiority with regard to prediction of MAS. Variability associated with Draize test outcome (e.g. in MAS values) must be considered in any future comparisons of in vivo and in vitro test results if the purpose is to predict in vivo response using in vitro data.     

Effects of sleeping in a chemical protective mask on sleep quality and cognitive performance

PURPOSE: We wanted to determine whether sleep is disrupted when soldiers sleep in a new chemical protective mask, the M40. Sleep quantity and quality, extent of protection provided by the mask during sleep, and next day performance were assessed. METHOD: After several days of training, 9 male soldiers slept with and without the M40 mask on four occasions. RESULTS: Soldiers were able to tolerate the mask for most or all of the night. However, sleep, as assessed by wrist-worn activity monitors, was significantly disturbed. Minutes (mean +/- SEM) of waking significantly increased, from 25 +/- 2.1 to 86 +/- 8.5 per night (p < 0.001), and number of awakenings rose from 8 +/- 0.6 to 20 +/- 0.9 (p < 0.0001). Soldiers reported that it took longer and was more difficult to fall asleep when wearing the mask. Errors on a choice reaction time task increased significantly and subjects reported greater fatigue and sleepiness the day after sleeping in the mask. Protection provided by the masks varied substantially among subjects and declined over the course of the study. Some soldiers were protected throughout the night but others were only protected intermittently. CONCLUSION: We conclude that sleeping in the chemical protective mask should only be done when necessary, given the adverse effects on sleep and daytime function, as well as the variability of protection, of the mask.     

Correcting temperature-sensitive protein folding defects

Recently, we found that different low molecular weight compounds, all known to stabilize proteins in their native conformation, are effective in correcting the temperature-sensitive protein folding defect associated with the deltaF508 cystic fibrosis transmembrane regulator (CFTR) protein. Here we examined whether the folding of other proteins which exhibit temperature-sensitive folding defects also could be corrected via a similar strategy. Cell lines expressing temperature-sensitive mutants of the tumor suppressor protein p53, the viral oncogene protein pp60src, or a ubiquitin activating enzyme E1, were incubated at the nonpermissive temperature (39.5 degrees C) in the presence of glycerol, trimethylamine N-oxide or deuterated water. In each case, the cells exhibited phenotypes similar to those observed when the cells were incubated at the permissive temperature (32.5 degrees C), indicative that the particular protein folding defect had been corrected. These observations, coupled with our earlier work and much older studies in yeast and bacteria, indicate that protein stabilizing agents are effective in vivo for correcting protein folding abnormalities. We suggest that this type of approach may prove to be useful for correcting certain protein folding abnormalities associated with human diseases.     

Changes in RBE of 14-MeV (d + T) neutrons for V79 cells irradiated in air and in a phantom: is RBE enhanced near the surface?

PURPOSE: The relative biological effectiveness (RBE) for inactivation of V79 cells was determined as function of dose at the Heidelberg 14-MeV (d + T) neutron therapy facility after irradiation with single doses in air and at different depths in a therapy phantom. Furthermore, to assess the reproducibility of RBE determinations in different experiments we examined the relationship between the interexperimental variation in radiosensitivity towards neutrons with that towards low LET 60Co photons. METHODS: Clonogenic survival of V79 cells was determined using the colony formation assay. The cells were irradiated in suspension in small volumes (1.2 ml) free in air or at defined positions in the perspex phantom. Neutron doses were in the range, Dt = 0.5-4 Gy. 60Co photons were used as reference radiation. RESULTS: The radiosensitivity towards neutrons varied considerably less between individual experiments than that towards photons and also less than RBE. However, the mean sensitivity of different series was relatively constant. RBE increased with decreasing dose per fraction from RBE = 2.3 at 4 Gy to RBE = 3.1 at 0.5 Gy. No significant difference in RBE could be detected between irradiation at 1.6 cm and 9.4 cm depth in the phantom. However, an approximately 20% higher RBE was found for irradiation free in air compared with inside the phantom. Combining the two effects, irradiation with 0.5 Gy free in air yielded an approximately 40% higher RBE than a dose of 2 Gy inside the phantom. CONCLUSION: The measured values of RBE as function of dose per fraction within the phantom is consistent with the energy of the neutron beam. The increased RBE free in air, however, is greater than expected from microdosimetric parameters of the beam and may be due to slow recoil protons produced by interaction of multiply scattered neutrons or to an increased contribution of alpha particles from C(n, alpha) reactions near the surface. An enhanced RBE in subcutaneous layers of skin combined with an increase in RBE at low doses per fraction outside the target volume could potentially have significant consequences for normal tissue reactions in radiotherapy patients treated with fast neutrons.     

"Back pain" in teenagers and young adults]

The studies aimed to estimate an incidence of the low back pain (LBP) in the youngsters and teenagers and correlating it with risk factors. A groups of 2,346 secondary school pupils (1,704 girls and 642 boys) of a mean age 17 +/- 1 yrs, and 970 high-school students (532 women and 438 men) of a mean age 24 +/- 2 yrs have been examined. Low back pain has been seen in 1,416 out of 2,346 secondary school pupils (60%), and in 32% of the examined students. Statistical analysis with chi 2 test has confirmed a correlation between LBP and such risk factors as the incorrect sedentary position (p < .001 for pupils, and p < .02 for students), and smoking (p < .001 for students and p < .02 for pupils).