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.     

Adherence to pharmacologic management of hypertension

Adherence to pharmacologic therapy of hypertension is low (in the range of 50-70%) and has important implications both for blood pressure control and cardiovascular complications. Based on a review of the literature using the levels of evidence grading technique, determinants of adherence to the pharmacologic therapy of hypertension have been assessed. Additionally, interventions to improve compliance were evaluated. Patient-centred, health care provider-centred and drug-specific factors have all been shown to affect adherence rates. We conclude that the extent of adherence to pharmacologic therapy is modifiable. Measurable improvements in adherence can be obtained from simplified medication regimens and a combination of behaviour strategies, including the tailoring of pill-taking to patients' daily habits and rituals, the advocacy of self-monitoring of pills and blood pressure, and the institution of reward systems.     

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.     

Insertional re-activation of a chloramphenicol acetyltransferase misfolding mutant protein

The deletion of nine residues from the C-terminus of the bacterialchloramphenicol acetyltransferase (CAT) results in depositionof the mutant protein in cytoplasmic inclusion bodies and lossof chloramphenicol resistance in Escherichia coli. This foldingdefect is relieved by C-terminal fusion of the polypeptide withas few as two residues. Based on these observations, efficientpositive selection for the cloning of DNA fragments has beendemonstrated. The cloning vector encodes a C-terminally truncatedCAT protein. Restriction sites in front of the stop codon allowthe insertion of target DNA, resulting in the production ofproperly folded CAT fusion proteins and regained chloramphenicolresistance. The positive selection of recombinants is accomplishedby growth of transformants on chloramphenicol-containing agarplates. The method appears particularly convenient for the cloningof DNA fragments amplified by the PCR because minimal informationto restore CAT folding can be included in the primers. The cloningof random sequences shows that the folding defect can be relievedby fusion to a wide variety of peptides, providing great flexibilityto the positive selection system. This vector may also contributeto the determination of the role of the C-terminus in CAT folding.     

Magnetometer spacing criterion for biomagnetic source currentimaging

A criterion for determining the maximum spacing between magnetometers for measuring the magnetic field is derived. A two-dimensional (2-D) filter model is employed to determine the maximum spatial frequency component present in the magnetic field that is above the spectral noise level. This maximum frequency component is then sampled at a rate greater than twice per period as indicated by the Nyquist criterion, yielding the required magnetometer spacing. It is shown that the rule-of-thumb employed in current clinical biomagnetic array systems, that the spacing between the coils should be approximately equal to the depth of the source, is adequate when the signal-to-noise power ratio is less than 28.4 (14.5 dB). The analysis also quantitatively demonstrates that reducing the separation between the measurement and source planes has a greater effect on the resolution than decreasing the noise level by the same factor. This result is important for employing high T_c superconductor magnetometers that allow thinner thermal insulating layers at the cost of higher thermal noise     

Polymer networks based on α,ω-methacrylate-terminated poly(1,3-dioxolane)

α,ω-Methacrylate-terminated poly(1,3-dioxolane)s (polyDXL) were synthesized by cationic ring-opening polymerization of DXL in the presence of methylene-bis(oxyethylmethacrylate) as transfer agent. If the initiator concentration is small compared with the transfer agent concentration, the molecular weights of the polymers are governed by the ratio of the reacted monomer to the reacted transfer agent. The α,ω-methacrylate-terminated polyDXLs obtained undergo free radical polymerization with formation of polyacetal networks. The properties of the networks as function of the molecular weight of the corresponding prepolymers are reported.     

Chemistry of the pyrrolo[1,2-alpha]benzimidazole antitumor agents: influence of the 7-substituent on the ability to alkylate DNA and inhibit topoisomerase II

This study addresses the influence the 7-substituent on the cytotoxicity of pyrrolo[1,2-alpha]-benzimidazole quinones possessing a 6-aziridinyl group (PBIs) and a 6-acetamido group (APBIs). Reduction of a PBI to the aziridinyl hydroquinone results in both nucleophile trapping (alkylation) and 1,5-sigmatropic shift reactions. The latter process is essentially an internal redox reaction wherein the hydroquinone causes reductive opening of the aziridinyl ring. The 7-substituent controls the fate of the aziridinyl ring by means of steric and electronic effects. An electron-rich 7-substituent favors the 1,5-sigmatropic shift reaction. If the 7-substituent distorts the 6-aziridinyl group from the conformation required for the 1,5-sigmatropic shift, then nucleophile trapping occurs. The 7-methyl substituent results in significant nucleophilic trapping, and the 7-unsubstituted and 7-methoxy substituents favor the 1,5-sigmatropic reaction. Thus, the 7-methyl PBIs show the most cytotoxicity of the analogues studied. The APBIs are cytotoxic only as quinones, and reduction to the hydroquinone results in loss of activity. Consistent with this observation, the change from 7-methyl to the more electron-rich 7-methoxy results in a substantial loss of APBI cytotoxicity as well as decreased topoisomerase II inhibition. The mechanism of inhibition is thought to involve the interacalation of only electron deficient APBIs into DNA.     

The effects of growth hormone in children with a GH deficiency: a report of 5 cases

The authors describe 5 cases, 3 boys and 2 girls, with idiopathic growth hormone deficiency in prepubertal age, treated with human growth hormone. In four of five cases the response to treatment with GH was relevant. Only in one case (F1) the response was negative. The results of this study confirm that rhGH is a safe and effective therapy in children with GHD.     

Low-temperature phase transformation in Li-10 at. % Mg

It is not known whether impaired hematopoiesis noted during human immunodeficiency virus (HIV) infection results from infection of stem/progenitor cells or of cells of the bone marrow microenvironment. Normal adherent primary stromal layers were exposed to HIV to determine which of this mixture of endothelial cells, fibroblasts, and macrophages are susceptible to the virus. Viral p24 in supernatants was noted with monocytotropic HIV-1Ada, HIV-1Ba-L, and HIV-1JR-FL but not with lymphotropic HIV-1LAI nor HIV-1MN strain, and only stromal macrophages expressed the viral antigens. Coculture of the layers with PHA-activated normal lymphocytes failed to rescue lymphotropic virus. No p24 was produced when macrophage-depleted stromal cells were exposed to either HIV-1Ba-L or HIV-1LAI; proviral DNA was then amplified by PCR in cells exposed to either virus, though coculture with lymphocytes rescued only HIV-1Ba-L. Altogether, these data indicate that macrophages are the major targets of HIV in cultured stromal layers. As virus replication in macrophages did not affect the profile of major cytokines involved in regulating hematopoiesis, HIV infection could alter hematopoiesis by other as yet unspecified mechanisms.     

Influence of interfacial microcracks on the elastic properties of composites

A model is established to quantify the influence of interfacial microcracks on the elastic properties of a particulate composite using a combination of theoretical and finite element analysis. A unique way to construct physical models which could accommodate both crack size and crack density is proposed. Based on energy principles, the influence of a dilute concentration of interfacial microcracks is first studied. The case of a finite concentration of microcracks is solved subsequently by combining the dilute concentration solutions and the differential scheme. Both cases agreed well with existing composite theories for the limiting condition of complete decohesion. The final model predicts the effective elastic properties as functions of both crack size and microcrack density.