Volume of resection in patients treated with breast conservation for ductal carcinoma in situ

The N-terminal domain (1-318 amino acids) of mouse NFkappaB (p65) has been purified to homogeneity from the soluble fraction of Escherichia coli cells expressing this protein. Its complex with a full-length ikappaB-alpha (MAD3, 1-317 amino acids) molecule was generated by binding the E. coli-derived ikappaB-alpha to the purified NFkappaB and purifying the complex by sequential chromatography. The stoichiometry of NFkappaB to ikappaB in the complex was determined to be 2 to 1 by light scattering and SDS-polyacrylamide gel electrophoresis. The secondary structure of the NFkappaB (p65) determined by Fourier-transform infrared (FTIR) spectroscopy is in good agreement with that of the p50 in the crystal structure of the p50/DNA complex, indicating that no significant structural change in NFkappaB occurs upon binding of DNA. The FTIR spectrum of the NFkappaB/ikappaB complex indicates that its secondary structure is composed of 17% alpha-helix, 39% beta-strand, 18% irregular structures, and 26% beta-turns and loops. By comparing these data to the FTIR data for NFkappaB alone, it is concluded that the ikappaB (MAD3) in the complex contains 35% alpha-helix, 27% beta-strand, 22% irregular structures, and 16% beta-turns and loops. Circular dichroism (CD) analysis of a shorter form of ikappaB (pp40) indicates that it contains at least 20% alpha-helix and that the ikappaB subunit accounts for nearly all of the alpha-helix present in the NFkappaB/ikappaB complex, consistent with the FTIR results. The stabilities of NFkappaB, ikappaB, and their complex against heat-induced denaturation were investigated by following changes in CD signal. The results indicate that the thermal stability of ikappaB is enhanced upon the formation of the NFkappaB/ikappaB complex.     

The comparative amino acid sequences, substrate specificities and gene or cDNA nucleotide sequences of some prokaryote and eukaryote amidinotransferases: implications for evolution

The amino acid sequences of the amidinotransferases and the nucleotide sequences of their genes or cDNA from four Streptomyces species (seven genes) and from the kidneys of rat, pig, human and human pancreas were compared. The overall amino acid and nucleotide sequences of the prokaryotes and eukaryotes were very similar and further, three regions were identified that were highly identical. Evidence is presented that there is virtually zero chance that the overall and high identity regions of the amino acid sequence similarities and the overall nucleotide sequence similarities between Streptomyces and mammals represent random match. Both rat and lamprey amidinotransferases were able to use inosamine phosphate, the amidine group acceptor of Streptomyces. We have concluded that the structure and function of the amidinotransferases and their genes has been highly conserved through evolution from prokaryotes to eukaryotes. The evolution has occurred with: (1) a high degree of retention of nucleotide and amino acid sequences; (2) a high degree of retention of the primitive Streptomyces guanine + cytosine (G + C) third codon position composition in certain high identity regions of the eukaryote cDNA; (3) a decrease in the specificities for the amidine group acceptors; and (4) most of the mutations silent in the regions suggested to code for active sites in the enzymes.     

Primary repair is superior to initial palliation in children with atrioventricular septal defect and tetralogy of Fallot

OBJECTIVE:The objective was to explore the best management algorithm for atrioventricular septal defect in conjunction with tetralogy of Fallot. METHODS: We reviewed the cases of 38 children referred to our division (March 1981-August 1997) who had atrioventricular septal defect associated with tetralogy of Fallot; 32 (84%) had Down syndrome. Twenty-one received initial palliation with a systemic-to-pulmonary artery shunt; of these, 2 (9.5%) died before complete repair. Thirty-one children underwent complete repair; 14 of these (45%) had undergone initial palliation (mean age at shunt 20 +/- 24 months). Right ventricular outflow obstruction was relieved by a transannular patch in 22 (71%); 14 (64% of 22) had a monocuspid valve inserted. Four required an infundibular patch. RESULTS: Two children (6.4%) died early after repair; 1 had undergone previous palliation. Patients with palliation underwent repair at an older age (78 vs 36 months), required longer ventilatory support (8 vs 4 days) and inotropic support (8 vs 4 days), and had longer intensive care stays (11 vs 6 days) and hospital stays (24 vs 15 days). Eleven children (35%) underwent reoperation, 7 (58%) for right ventricular outflow reconstruction and pulmonary arterioplasty. Reoperation was more frequent in the palliation group than in the primary operation group (64% vs 12%). The single late death was related to a reoperation in the palliation group. CONCLUSIONS: Atrioventricular septal defect with tetralogy of Fallot can be repaired with a low mortality rate. Initial palliation with a shunt resulted in a more complex postoperative course and a higher reoperative rate. Primary repair is superior to initial palliation with later repair.     

Vectorial competence of Glossina tachinoides Westwood and Glossina palpalis gambiensis Vanderplank infected by Trypanosoma brucei brucei EATRO 1125]

In this work the relationship between the proliferation of bovine corneal epithelial cells and PGE2 has been studied. Our data indicate that PGE2 plays an important role in the growth of corneal epithelial cells. Actually, epithelial cells cultured on a keratocyte feeder-layer and exposed to indomethacin, a cyclooxygenase inhibitor, have shown a decrease in growth rate at drug concentrations which otherwise did not induce a reduction in the viability of the keratocytes as well as in epithelial cells in separate cultures. This effect has been reversed by an exogenous PGE2 addition to the culture media. Moreover, significant increases have been found in the growth of epithelial cells cultured in the presence of keratocytes, with basal medium and with conditioning medium after adding exogenous PGE2 at concentrations equal to or lower than 10(-6) M. Significant decreases in the dimensions of the corneal epithelial cells have been found only when PGE2 has been added to basal and to conditioning medium, suggesting that the autacoid maintains cell dimension and morphology. The appearance of keratins with high molecular weight (54 and 57 kDa) coupled with the tendency to stratification of the cells cultivated with media supplemented with PGE2, indicates that the autacoid could favour cell differentiation. The action of PGE2 on the corneal epithelial cells does not seem to be influenced by the presence of the fibroblasts and their products, since PGE2 has induced increases in cell growth and morphological variations, independent of cultural conditions and therefore also only in the presence of basal medium.     

Evidence for a Turner syndrome locus or loci at Xp11.2-p22.1

Turner syndrome is the complex human phenotype associated with complete or partial monosomy X. Principle features of Turner syndrome include short stature, ovarian failure, and a variety of other anatomic and physiological abnormalities, such as webbed neck, lymphedema, cardiovascular and renal anomalies, hypertension, and autoimmune thyroid disease. We studied 28 apparently nonmosaic subjects with partial deletions of Xp, in order to map loci responsible for various components of the Turner syndrome phenotype. Subjects were carefully evaluated for the presence or absence of Turner syndrome features, and their deletions were mapped by FISH with a panel of Xp markers. Using a statistical method to examine genotype/phenotype correlations, we mapped one or more Turner syndrome traits to a critical region in Xp11.2-p22.1. These traits included short stature, ovarian failure, high-arched palate, and autoimmune thyroid disease. The results are useful for genetic counseling of individuals with partial monosomy X. Study of additional subjects should refine the localization of Turner syndrome loci and provide a rational basis for exploration of candidate genes.     

Studies of bioaccumulation and biotransformation of PCBs in mustelids based on concentration and congener patterns in predators and preys

Bioaccumulation of non-, mono-, and di-ortho-substituted chlorobiphenyls (CBs) was investigated in four species of mustelids (weasel, stoat, polecat, and otter) and their preys, from a restricted area in the northern part of The Netherlands. Diets of these mustelids ranged from terrestrial (weasel, stoat, and polecat) to aquatic (otter). Diet-specific biomagnification factors (BMFs), CB in diet relative to CB in mustelids, were calculated for the sum of 28 congeners (SigmaCB), for the sum of the toxic equivalent concentration (SigmaTEQ) and on an individual congener basis. Biotransformation was studied in relation to structural CB properties (vicinal H-atom substitution). In addition, the methylsulphonyl CB-metabolites were determined. The concentration of SigmaCB on lipid weight basis increased in the order weasel < stoat < polecat < otter. On the basis of SigmaTEQ, the order changed to weasel < polecat < stoat < otter. Most of the differences in BMFs between the CBs could be explained by the vicinal H-atom structure-activity rules. For all mustelids, the lowest BMFs were found for congeners with vicinal H-atoms in the meta, para position. Indications were found that all mustelid species can metabolize these congeners. For some of the CBs, their methylsulphonyl-CB metabolites were determined and found to be present in concentrations up to 350-fold higher than those of the parent compounds. In addition, the non-ortho CBs 126 and 169 are selectively retained in the liver of weasel, stoat, and otter. These CBs had the highest BMFs of all congeners. However, rather surprisingly, in polecat the highest BMFs were found for di-ortho-substituted CBs. This animal was able to metabolize all congeners with vicinal H-atoms in the ortho and meta position (non- and mono-ortho CBs). The information concerning the differences in bioaccumulation of CBs for closely related mustelid species increased the understanding of reported differences in PCB toxicity between mink and ferrets, and suggest that weasel, stoat, and otter are at least as sensitive to CBs as are mink, while polecats are less sensitive. As otter is exposed to much higher concentrations of CBs trough their diet than weasel and stoat, the toxic threat of CBs will be the greatest for this animal.     

Artemisinin-derived sesquiterpene lactones as potential antitumour compounds: cytotoxic action against bone marrow and tumour cells

Epidemiologic and public health researchers frequently include several dependent variables, repeated assessments, or subgroup analyses in their investigations. These factors result in multiple tests of statistical significance and may produce type 1 experimental errors. This study examined the type 1 error rate in a sample of public health and epidemiologic research. A total of 173 articles chosen at random from 1996 issues of the American Journal of Public Health and the American Journal of Epidemiology were examined to determine the incidence of type 1 errors. Three different methods of computing type 1 error rates were used: experiment-wise error rate, error rate per experiment, and percent error rate. The results indicate a type 1 error rate substantially higher than the traditionally assumed level of 5% (p < 0.05). No practical or statistically significant difference was found between type 1 error rates across the two journals. Methods to determine and correct type 1 errors should be reported in epidemiologic and public health research investigations that include multiple statistical tests.     

Time to relapse has prognostic value in patients with aggressive lymphoma enrolled onto the Parma trial

PURPOSE: The purpose of this study was to investigate the prognostic value of time to relapse in 188 adult patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) included on the Parma trial at the time of their first relapse. PATIENTS AND METHODS: The median follow-up of these patients is 102 months after registration onto the Parma study. Time to relapse was calculated from initial diagnosis, and a cutoff of 12 months was used to separate 77 patients defined as early relapse from 111 patients defined as late relapse. RESULTS: Patients with early and late relapses had significantly different overall response rates to salvage therapy with two courses of dexamethasone, high-dose cytarabine, and cisplatin (DHAP; 40% v 69%; P=.00007) and different 8-year survival rates (13% v 29%; P=.00001). Features at relapse with a negative prognostic value in univariate analysis were higher than normal lactic dehydrogenase (LDH) levels, tumor size greater than 5 cm, Ann Arbor stages III to IV, and Karnofsky score less than 80%. Therefore, multivariate analyses were performed. Time to relapse (P=.001) and LDH levels at relapse (P=.003) had independent prognostic value, whereas tumor size did not reach statistical significance in the logistic model that predicted overall response after two courses of DHAP. The study of prognostic factors for overall survival (OS) and progression-free survival (PFS) confirmed the prognostic value of time to relapse (P < .0001 for OS and P=.005 for PFS) independent of response or treatment after two courses of DHAP. CONCLUSION: Time to relapse may be used to stratify patients at time of first relapse of intermediate to high-grade non-Hodgkin's lymphoma.     

Randomized controlled trial of omeprazole or endoscopy in patients with persistent dyspepsia: a cost-effectiveness analysis

BACKGROUND: Cost-effectiveness analysis, Helicobacter pylori research and the development of proton pump inhibitors are having an increasing impact on the management of dyspepsia. However, clinical trials have not always included both H. pylori diagnosis and proton pump inhibitors in their protocols. METHODS: Patients who were referred for upper gastrointestinal endoscopy by their general practitioner were randomized to either prompt endoscopy followed by directed medical treatment (conventional group, n=38), or to empirical treatment with omeprazole and, in the case of symptom relapse, serological screening for H. pylori infection followed by eradication therapy in seropositive patients (empirical group, n=42). The study lasted for up to 1 year. RESULTS: In the empirical group, only 13 patients (31%) underwent endoscopy. The average number of days for which the patients kept records of their dyspeptic symptoms was 266 (95% CI: 226-307) in the empirical group, of which 166 (95% CI: 128-204) were symptom-free. In the conventional group, 159 (95% CI: 119-198) out of 255 days (95% CI: 209-302) were recorded as symptom-free. The average medical cost in the empirical group was $284 (95% CI: 218-350) and in the conventional group $491 (95% CI: 383-600). In the empirical group, two malignancies were found, whereas in the conventional group one malignancy was found. CONCLUSIONS: The empirical drug treatment strategy in patients with persistent dyspeptic symptoms resulted in 69% fewer diagnostic endoscopies with lower medical costs and equal effectiveness in the first year, compared to prompt endoscopy followed by directed medical treatment.