Luminol and lucigenin amplified chemiluminescence and lipidperoxidation with brain microsomes from rats during ontogenetic development

During the 1980s, the ecologic association of conjugated estrogens with endometrial cancer changed from positive to negative in a prepaid health plan. During the same period, use of progestins increased dramatically. We investigated whether the latter increase could explain the reversal of the estrogen-cancer association. Endometrial cancer incidence was estimated from cases recorded in the health plan registry divided by the number of women over age 45 years. Conjugated estrogens usage was measured as milligrams prescribed per woman per year and progestin was measured as tablets per woman per year, both based upon pharmacy records. Graphical and regression methods were used to analyze the resulting ecologic data. In a log-linear regression of incidence on conjugated estrogens and medroxyprogesterone usage, estrogen usage had a strong positive association with incidence, while medroxyprogesterone had a strong negative association with incidence. The change in the direction of the ecologic association between estrogen and endometrial cancer that occurred in 1984 continued until 1993, suggesting that the decline in endometrial cancer incidence and concomitant increase in conjugated estrogens usage since 1984 is explained by the increasing use of progestins. The data are entirely consistent with the hypothesis that progestins can protect against most of the excess risk conferred by conjugated estrogens, although the ecologic nature of the data prohibits drawing further inferences.     

Percutaneous endoscopic gastrostomy (PEG) in upper gastrointestinal tract occlusion in gynecologic oncology

BACKGROUND AND AIMS: Intestinal obstruction is a frequent cause of death in patients suffering from gynecological cancer, who have undergone multiple treatment in the form of surgery and/or chemotherapy and/or radiotherapy. The usual form of rescue treatment consists in the use of a nasogastric tube to administer support and analgesic treatment. Surgical gastrostomy is not a viable proposition in these extremely weak patients with large masses compressing and displacing the stomach. Percutaneous endoscopic gastrostomy (PEG), a technique first introduced for nutritional purposes, can be beneficially used to achieve decompression in these patients. METHODS: PEG was performed in a total of 67 patients who had already undergone multiple treatment for abdominal-pelvic neoplasia with upper gastrointestinal obstruction, who could no longer be operated and who had a life expectancy of less than sixty days. In three cases positioning was not possible owing to the lack of transillumination of the gastric and abdominal wall. 54/64 patients had previously undergone at least two operations. RESULTS: Esophagogastric lesions were found in 29% of patients, some of which were attributed to the nasogastric tube. Symptomatic wellbeing was obtained in 76.5% a few days after PEG. PEG remained in situ from 4 to 472 days. Slight peristomal infection was observed in 9% of cases. In seven cases it was necessary to add octreotide owing to the reappearance of symptoms. CONCLUSIONS: PEG is relatively easy to use and allows obstructive symptoms to be resolved in the majority of patients. Special medical skills are not required and the patient may be easily managed at home together with support therapy and pain management. Once PEG has been performed, it is possible to take fluids and semi-liquid foods, offering the patient a chance to taste flavours which have often been forgotten. PEG enables neoadjuvant chemotherapy to be performed in patients with previously untreated intestinal obstruction.     

Cell-mediated immunological responses in cervical and vaginal cancer patients immunized with a lipidated epitope of human papillomavirus type 16 E7

Human papillomavirus (HPV) infection has been causally associated with cervical cancer. We tested the effectiveness of an HLA-A*0201-restricted, HPV-16 E7 lipopeptide vaccine in eliciting cellular immune responses in vivo in women with refractory cervical cancer. In a nonrandomized Phase I clinical trial, 12 women expressing the HLA-A2 allele with refractory cervical or vaginal cancer were vaccinated with four E786-93 lipopeptide inoculations at 3-week intervals. HLA-A2 subtyping was also performed, and HPV typing was assessed on tumor specimens. Induction of epitope-specific CD8+ T-lymphocyte (CTL) responses was analyzed using peripheral blood leukapheresis specimens obtained before and after vaccination. CTL specificity was measured by IFN-gamma release assay using HLA-A*0201 matched target cells. Clinical responses were assessed by physical examination and radiographic images. All HLA-A*0201 patients were able to mount a cellular immune response to a control peptide. E786-93-specific CTLs were elicited in 4 of 10 evaluable HLA-A*0201 subjects before vaccination, 5 of 7 evaluable HLA-A*0201 patients after two vaccinations, and 2 of 3 evaluable HLA-A*0201 cultures after all four inoculations. Two of three evaluable patients' CTLs converted from unreactive to reactive after administration of all four inoculations. There were no clinical responses or treatment toxicities. The ability to generate specific cellular immune responses is retained in patients with advanced cervical cancer. Vaccination with a lipidated HPV peptide epitope appears capable of safely augmenting CTL reactivity. Although enhancements of cellular immune responses are needed to achieve therapeutic utility in advanced cervical cancer, this approach might prove useful in treating preinvasive disease.     

Adrenocorticotropin and cortisol hyperresponsiveness to hexarelin in patients with Cushing's disease bearing a pituitary microadenoma, but not in those with macroadenoma

We previously reported that in Cushing's disease (CD) the ACTH- and cortisol (F)-releasing activity of Hexarelin (HEX), a GH secretagogue, is exaggerated with respect to that in normal subjects and is higher than that of human CRH (hCRH), but it is absent in Cushing's syndrome. Our aim was to extend the study about the effects of HEX (2.0 microg/kg, iv) on ACTH and F secretion in 21 patients with CD (3 men and 18 women, 16-68 yr old). Based on magnetic resonance imaging, 15 CD patients had pituitary microadenoma, and 6 had macroadenoma. The results in CD patients were compared with those in 27 normal age-matched controls (NS; 10 men and 17 women, 24-69 yr old). Basal ACTH and F levels in CD were similar in patients with microadenom (mean+/-SEM, 78.3+/-7.2 pg/mL and 237.1+/-23.6 microg/L, respectively) and macroadenoma (57.4+/-9.0 pg/mL and 196.9+/-20.1 microg/L, respectively) and were higher (P < 0.001) than those in NS (17.7+/-2.0 pg/mL and 115.3+/-6.7 microg/L, respectively). In microadenoma CD patients, HEX induced marked ACTH and F increases (delta peak, mean+/-SEM: 261.2+/-77.6 pg/mL and 226.1+/-87.2 microg/L, respectively), which were higher (P < 0.04) than those induced by hCRH (45.6+/-16.9 pg/mL and 84.6+/-25.7 microg/L, respectively). Moreover, in microadenoma CD patients, the ACTH and F responses to HEX were higher (P < 0.001) than those in NS (18.5+/-4.0 pg/mL and 36.1+/-6.8 microg/L, respectively). In macroadenoma CD patients, HEX induced a slight, but significant increase (P < 0.02) in ACTH and F levels (33.9+/-18.0 pg/mL and 89.6+/-34.3 microg/L, respectively), which was not significantly different from that elicited by hCRH (20.0+/-7.0 pg/mL and 54.8+/-21.3 microg/L, respectively). In macroadenoma CD patients, the ACTH and F responses to HEX and hCRH were, in turn, similar to those in NS. In conclusion, our findings demonstrate that the ACTH and F hyperresponsiveness to HEX is present in Cushing's disease with micro-, but not macro- ACTH-secreting pituitary adenoma. This finding agrees with other evidence pointing toward differences in the hormonal behavior between micro- and ACTH-secreting pituitary macroadenomas.     

Closed-loop expressions of minimum energy control for single-inputlinear digital systems

Closed-loop expressions for the minimum energy control of a single-input linear digital system are described. They are obtained by two different methods. The optimal inputs are given by state feedback with the bounded variable gains. The gains are independent of the initial state of the system     

Duration of spinal anaesthesia is determined by the partition coefficient of local anaesthetic

We have compared the duration of motor block produced by four local anaesthetics administered into a chronically implanted subarachnoid catheter in rabbits. Each group (n = 6) received four different doses of amethocaine, bupivacaine, lignocaine or procaine, and the duration of the resulting motor block was assessed. Dose-response curves were plotted for each drug. As a measure of activity of the anaesthetics, we used the dose of each drug required to produce block of 60-min duration (D60 min) and the correlation between D60 min and different drug properties was examined. An inverse linear correlation (r = 0.995; P < 0.01) was observed between log D60 min and the log of the partition coefficient of the local anaesthetics. No correlation was found between the effect and degree of protein binding, pKa or molecular weight. These results suggest that, in spinal anaesthesia, the partition coefficient could be used as a predictor of the duration of anaesthetic action.