Incidence Of Positive Responses Research Articles

The impact of oxaliplatin-based chemotherapy for colorectal cancer on the autonomous nervous system.

The oxaliplatin (ΟΧΑ)-based regimens FOLFOX and XELOX can cause peripheral neuropathy. It is unknown if ΟΧΑ, alone or in combination regimens, affects the Autonomous Nervous System (ANS). Accordingly, we evaluated the impact of ΟΧΑ-based chemotherapy on the ANS. We enrolled 36 patients with colorectal cancer, treated with adjuvant mFOLFOX6 or XELOX chemotherapy, and 22 healthy volunteers. For the assessment of ANS function, participants completed a questionnaire and underwent neurophysiological examination at three time points (baseline, 3-4months and 6-8months after the first chemotherapy cycle). ANS testing included assessment of the adrenergic cardiovascular function (orthostatic hypotension-OH), parasympathetic heart innervation (ratio 30/15) and Sympathetic Skin Response (SSR). The values of the 30/15 ratio were significantly reduced at the two time point assessments compared to baseline (Wilcoxon signed ranks test, both P<0.001), while patients had more often diastolic OH at the 6-8month evaluation compared to baseline (P=0.039). In contrast, SSR was not affected. The incidence of positive responses in the questionnaire assessing the subjective impact of symptoms attributable to ANS dysfunction was higher at the two time points compared to baseline (P=0.036 and P=0.020). Oxaliplatin-based chemotherapy is associated with significant effects on the adrenergic cardiovascular reaction and the parasympathetic heart innervation, whereas SSR remains untouched.

Application of a 4-h human patch test method for comparative and investigative assessment of skin irritation.

A human 4-h patch test has recently been developed for testing the irritation hazard potential of chemicals. The original method was developed for comparative irritation assessments relative to benchmark irritants using simple statistical tests. In this context, the method has been shown to be robust in intralaboratory testing over time. Recent interlaboratory testing has also established the consistency of the method in assessment of the relative irritation potential of selected chemicals. These data help to position the method as a suitable replacement for animal test methods in assessment of skin irritation hazard. In addition, the method has great utility for investigating different parameters of clinical skin irritation. Using kinetic response patterns and curve fitting analysis, we have compared the relative irritation potential of chemicals in greater detail, using as a basis the time required for test subjects to respond as well as the incidence of positive responses. Also, using the response to 20% sodium dodecyl sulfate (SDS) as a benchmark, we've been able to examine the intersubject variation in clinical skin irritation responses. In general, subjects most reactive to 20% SDS, in terms of the exposure time required to produce a positive response, were relatively more sensitive to a 2nd irritant chemical as well. However, this was not an absolute correlation in that some test subjects showed divergent patterns of response. The method was also used to compare directly the relative skin reactivity of different populations, based on race (Caucasian versus Asian) or on neurosensory skin sensitivity. Our results using this acute exposure test method indicate little difference in visually assessed skin irritation among these diverse human subpopulations.

Tegafur-Uracil (UFT) Plus Folinic Acid in Advanced Rectal Cancer

We previously reported positive results to Tegafur-Uracil (UFT) chemotherapy in a group of patients with advanced rectal cancer. We have continued the study and now report the effectiveness of UFT plus folinic acid (FA) in 52 patients with advanced rectal cancer. The therapeutic schedule was UFT, 600 mg/m2/day x 14 days p.o. + FA, 90 mg/m2/day x 14 days p.o. Fifty-two out of a total of 56 patients were evaluated for response and toxicity. A higher incidence of positive responses in patients without previous chemotherapy was appreciated. Twenty-one of the 52 evaluated patients showed a partial response (PR). Responses were strongly correlated with previous chemotherapy (14/20; 70% PR of cases without previous chemotherapy vs 7/32; 22% of cases with previous chemotherapy). All responding patients came forward with a median time to progression of 8.2 months (19.6 months for patients without previous chemotherapy vs 7.7 months for patients with previous chemotherapy, P < 0.01). We concluded that the UFT plus FA could be a treatment of choice for patients with advanced rectal cancer.

Screening for delayed-hypersensitivity in Italian children: Multicentric study by multitest skin testing

The Multitest skin test allows the simultaneous intradermal application of seven standardized recall antigens in a reproducible manner. Response reading is based on a scoring system that distinguishes between normal and diminished delayed hypersensitivity (DH). To determine incidence and size of DH responses for each antigen in relation to age and sex in healthy Italian children, a multicentric study was performed on a representative paediatric population of 491 subjects (285 males and 296 females) aged from 4 months to 16 years. In both sexes DH reactivity as measured by score and number of positive responses increased significantly with age. The incidence of anergy was 8.8% for the whole population and decreased significantly with age in both sexes. Incidence of positive responses was highest for tetanus and diphteria toxoids, intermediate for Candida, Proteus and Streptococcus, and lowest for tuberculin and Trichophyton antigens. There was no significant difference between sexes in the incidence of positive response to each antigen.

A Double-Blind Study of Symptom Provocation to Determine Food Sensitivity

Some claim that food sensitivities can best be identified by intradermal injection of extracts of the suspected allergens to reproduce the associated symptoms. A different dose of an offending allergen is thought to "neutralize" the reaction. To assess the validity of symptom provocation, we performed a double-blind study that was carried out in the offices of seven physicians who were proponents of this technique and experienced in its use. Eighteen patients were tested in 20 sessions (two patients were tested twice) by the same technician, using the same extracts (at the same dilutions with the same saline diluent) as those previously thought to provoke symptoms during unblinded testing. At each session three injections of extract and nine of diluent were given in random sequence. The symptoms evaluated included nasal stuffiness, dry mouth, nausea, fatigue, headache, and feelings of disorientation or depression. No patient had a history of asthma or anaphylaxis. The responses of the patients to the active and control injections were indistinguishable, as was the incidence of positive responses: 27 percent of the active injections (16 of 60) were judged by the patients to be the active substance, as were 24 percent of the control injections (44 of 180). Neutralizing doses given by some of the physicians to treat the symptoms after a response were equally efficacious whether the injection was of the suspected allergen or saline. The rate of judging injections as active remained relatively constant within the experimental sessions, with no major change in the response rate due to neutralization or habituation. When the provocation of symptoms to identify food sensitivities is evaluated under double-blind conditions, this type of testing, as well as the treatments based on "neutralizing" such reactions, appears to lack scientific validity. The frequency of positive responses to the injected extracts appears to be the result of suggestion and chance.

The cyclopentolate provocative test in suspected or untreated open-angle glaucoma. I. Effect on intraocular pressure.

The mydriasis provocative test with 1% cyclopentolate (CPT) was performed on 218 patients with suspected or untreated open-angle glaucoma, on 431 eyes in all. Gonioscopy was performed before and during the test to ensure that te chamber angles were open throughout. The effect of cyclopentolate on intraocular pressure (10P) in these eyes is reported in the present paper. The mean change in IOP (+/-SD) During CPT was +2.5 +/- 3.1 mmHg in the glaucoma group (196 eyes), +0.4 +/- 2.5 mmHg in the group with suspicion of open-angle glaucoma (235 eyes), and +1.4 +/- 2.9 mmHg in the total series. The difference in IOP change between the groups with glaucoma and suspected glaucoma is statistically highly significant. The incidence of positive responses (IOP rise larger than or equal to 8 mmHg) in the glaucoma group (8.7%: 17 eyes) was significantly higher than in the suspicion group (1.7%: 4 eyes). Significant IOP elevations in the total series were demonstrated in 21 eyes of 18 patients (4.9%). Including the borderline cases, IOP elevations larger than or equal to 5 mmHg were also significantly more frequent in eyes with glaucoma (24.0%: 47 eyes) than in eyes with suspected glaucoma (11.9%: 28 eyes). The occurrence and magnitude of positive responses were not dependent on the initial IOP level. Further analysis of the responder group and clinical studies of the mechanism of IOP elevation on the same patients are presented in parts II and III.