Routine pre- and post-neoadjuvant chemotherapy fitness testing is not indicated for oesophagogastric cancer surgery.

Introduction There is a known correlation between anaerobic threshold (AT) during cardiopulmonary exercise testing and development of cardiopulmonary complications in high-risk patients undergoing oesophagogastric cancer surgery. This study aimed to assess the value of routine retesting following neoadjuvant chemotherapy. Methods Patients undergoing neoadjuvant chemotherapy with subsequent oesophagogastric cancer surgery with pre- and post-neoadjuvant chemotherapy cardiopulmonary exercise data were identified from a prospectively maintained database. Measured cardiopulmonary exercise variables included AT and maximum oxygen uptake at peak exercise (VO2 peak). Anaerobic threshold values within 1 ml/kg/minute were considered static. Patients were grouped into AT ranges of less than 9 ml/kg/minute, 9-11 ml/kg/minute and greater than 11 ml/kg/minute. Outcome measures were unplanned intensive care stay, postoperative cardiovascular morbidity and mortality. Results Between May 2008 and August 2017, 42 patients from 675 total resections were identified, with a mean age of 65 years (range 49-84 years). Mean pre-neoadjuvant chemotherapy AT was 11.07 ml/kg/minute (standard deviation, SD, 3.24 ml/kg/minute, range 4.6-19.3 ml/kg/minute) while post-neoadjuvant chemotherapy AT was 11.19 ml/kg/minute (SD 3.05 ml/kg/minute, range 5.2-18.1 ml/kg/minute). Mean pre-neoadjuvant chemotherapy VO2 peak was 17.13 ml/kg/minute, while post-chemotherapy this mean fell to 16.59 ml/kg/minute. Some 44.4% of patients with a pre-chemotherapy AT less than 9 ml/kg/minute developed cardiorespiratory complications compared with 42.2% of those whose AT was greater than 9 ml/kg/minute (P = 0.914); 63.6% of patients in the post-neoadjuvant chemotherapy group with an AT less than 9 ml/kg/minute developed cardiorespiratory complications. There was no correlation between direction of change in AT and outcome. Conclusion In our patient population, neoadjuvant chemotherapy does not appear to result in a significant mean reduction in cardiorespiratory fitness. Routine pre- and post-neoadjuvant chemotherapy cardiopulmonary exercise testing is currently not indicated; however, larger studies are required to demonstrate this conclusively.

Comparison of endoscopic laser therapy and self expanding metal stents for palliation in patients with non-resectable oesophageal carcinoma.

BACKGROUND: There are currently limited data on the comparative success of endoscopic laser therapy (NLT) and self expanding metal stents (SEMS) as palliative measures in patients with non-resectable oesophageal cancer. This study aims to assess and compare the outcomes of these methods of endoscopic palliation. METHODS: Patients with non-curative oesophageal/gastro-oesophageal cancers with dysphagia were identified prospectively and consented to swallow assessment and follow-up. Patients underwent SEMS or NLT at the discretion of the treating endoscopist. Initial standardised swallow scores (0-4) were assessed. All subsequent interventions were recorded as well as survival. RESULTS: 31 patients were recruited (30M vs 8F, mean age 70.8). There was no significant difference in age, sex or chemotherapy treatment between groups. 19(61%)patients underwent NLT as primary procedure. 20(64.5%) patients required subsequent intervention(s) (median 1, range 0-8). Primary NLT patients were more likely to require subsequent therapy (p = 0.004) and multiple procedures (p = 0.001). 8(42.1%)patients initially undergoing NLT subsequently required SEMS, while no SEMS patients underwent subsequent NLT. Swallow scores of 1 or 2 were more likely to be maintained with NLT while scores of 3 or 4 were more likely to progress to SEMS (p = 0.039). Time to repeat procedure was greater in the SEMS group (p = 0.001). Median survival was 133 days for NLT vs 60 days for SEMS (p = 0.412). CONCLUSION: In this series, patients selected for NLT had a trend towards longer survival, but were more likely to require repeated procedures. Those with lower early initial dysphagia scores were more likely to be maintained by NLT alone.

A comparison of the left thoracoabdominal and Ivor-Lewis esophagectomy.

The purpose of this study was to assess the oncological outcomes of a large multicenter series of left thoracoabdominal esophagectomies, and compare these to the more widely utilized Ivor-Lewis esophagectomy. With ethics approval and an established study protocol, anonymized data from five centers were merged into a structured database. The study exposure was operative approach (ILE or LTE). The primary outcome measure was time to death. Secondary outcome measures included time to tumor recurrence, positive surgical resection margins, lymph node yield, postoperative death, and hospital length of stay. Cox proportional hazards models provided hazard ratios (HR) with 95% confidence intervals (CI) adjusting for age, pathological tumor stage, tumor grade, lymphovascular invasion, and neoadjuvant treatment. Among 1228 patients (598 ILE; 630 LTE), most (86%) had adenocarcinoma (AC) and were male (81%). Comparing ILE and LTE for AC patients, no difference was seen in terms of time to death (HR 0.904 95%CI 0.749-1.1090) or time to recurrence (HR 0.973 95%CI 0.768-1.232). The risk of a positive resection margin was also similar (OR 1.022 95%CI 0.731-1.429). Median lymph node yield did not differ between approaches (LTE 21; ILE 21; P = 0.426). In-hospital mortality was 2.4%, significantly lower in the LTE group (LTE 1.3%; ILE 3.6%; P = 0.004). Median hospital stay was 11 days in the LTE group and 14 days in the ILE group (P < 0.0001). In conclusion, this is the largest series of left thoracoabdominal esophagectomies to be submitted for publication and the only one to compare two different transthoracic esophagectomy strategies. It demonstrates oncological equivalence between operative approaches but possible short- term advantages to the left thoracoabdominal esophagectomy.

Current practice in bowel preparation for colorectal surgery: a survey of the members of the Association of Coloproctology of GB & Ireland.

AIM: Recent meta-analyses have suggested that mechanical bowel preparation is not beneficial in patients undergoing colorectal resection. This study aimed to assess current surgical practice in the UK. METHOD: Three hundred and ninety-eight members of the Association of Coloproctology of GB & Ireland were invited to complete an online survey to ascertain their current practice for bowel preparation. RESULTS: One hundred and ninety-nine surgeons completed the survey, of whom 95 (48%) routinely performed laparoscopic resection. The proportions using full bowel preparation for open vs laparoscopic surgery were, respectively, 9.5%vs 16.8% for right hemicolectomy, 43.4%vs 40.2% for left hemicolectomy, 20.5%vs 22.5% for an abdominoperineal resection and 72.2%vs 63.6% for low anterior resection. Among the surgeons who participated, 13.6% changed their practice between doing the same procedure open and laparoscopically, 76% of surgeons routinely defunctioned a low anterior resection. Of these, 22% did not feel that full bowel preparation was necessary before formation of an ileostomy. CONCLUSION: The study demonstrates that a large proportion of patients still receive full bowel preparation despite recent advice to the contrary.

Orthodontic status and treatment need of 12-year-old children in South Africa using the Dental Aesthetic Index.

OBJECTIVE: The aim of this study was to determine the prevalence and severity of malocclusion and orthodontic treatment needs in a sample of 12-year-old South African school children using the Dental Aesthetic Index (DAI), and to assess the relationship between malocclusion and certain socio-demographic variables. METHODOLOGY: The sample comprised 6142, 12-year-old children attending school in seven of the nine provinces of South Africa. For each subject the standard demographic information such as gender, population group, location type and employment status of the parents was collected, after which an intra-oral examination for occlusal status using the DAI was performed. Before the survey, the examiners were calibrated and trained and only examiners with an agreement score greater or equal to 80 per cent were included in the final study. RESULTS: The results showed that 47.7 per cent of the children in the sample presented with good occlusion or minor malocclusion, just over 52.3 per cent presented with identifiable malocclusion, a DAI score larger than 26. Of these, 21.2 per cent had definite malocclusion, 14.1 per cent had severe malocclusion and 16.9 per cent had very severe or handicapping malocclusion. Malocclusion as defined in this study was found to be significantly associated with the different population groups in South Africa, with gender and with dentition stage, but not with the location type or the employment status of parents. CONCLUSIONS: The results of this study show a high prevalence of malocclusion in 12-year-old South African children. The findings provide reliable base-line data regarding the prevalence, distribution and severity of malocclusion as well as useful epidemiological data on the orthodontic treatment needs of 12-year-old children in South Africa.

Urokinase receptor antagonists: discovery and application to in vivo models of tumor growth.

Urokinase receptor antagonists based on the growth factor domains of both human and murine urokinase which show sub-nanomolar affinities for their homologous receptors have been expressed as recombinant proteins. Further modification of these molecules by preparing fusions with the constant region of human IgG has led to molecules with high affinities and long in vivo half-lives. Smaller peptidic inhibitors have been obtained by a combination of bacteriophage display and peptide analog synthesis. All of these molecules inhibit the binding of the growth factor domain of uPA to the uPA receptor and enhance binding of the uPA receptor to vitronectin. Protein uPA receptor antagonists were tested in an in vivo tumor model using the human breast carcinoma MDAmb231 in immunodeficient mice. Both human and murine receptor antagonists showed significant inhibition of primary tumor growth, demonstrating that in vivo, both tumor and stromal cell uPA receptor dependent plasminogen activation can modulate tumor growth.

Identification of the urokinase receptor as an adhesion receptor for vitronectin.

Urokinase receptors, expressed on surfaces of many cell types, focus to the pericellular space plasminogen-dependent proteolysis important in matrix remodeling and cell movement. We now report that the urokinase receptor (uPAR) is also a high affinity (Kd < 30 nM) receptor for vitronectin. Recombinant uPAR binds vitronectin in the absence of urokinase, but vitronectin binding is promoted by concurrent receptor binding of either urokinase or fragments thereof containing its uPAR binding domain. Stable epithelial cell transfectants expressing membrane-anchored uPAR, but not cells expressing soluble uPAR, become strongly adhesive with altered morphology in the absence of urokinase. These observations identify a new class of vitronectin receptor and imply a duality in function for the receptor that intrinsically links matrix adhesion to regulation of protease activity. Increases in urokinase receptor expression known to be associated with cellular activation and malignant transformation could modulate cellular trafficking and function by promoting attachment to vitronectin.

Learning style and personality type.

To investigate the relations between the Myers-Briggs Type Indicator and the Gregorc Style Delineator and to examine the construct validity of the Style Delineator, 41 undergraduate students preparing to be teachers were given both tests. Observed differences in learning styles by personality type partially support the construct validity of the Style Delineator. Judging individuals (n = 25) tended to perceive themselves as concrete sequential thinkers as opposed to perceptive individuals (n = 16) who thought of themselves as concrete random thinkers. Feeling types (n = 29) tended to prefer random modes of thinking.

Work values of black, unwed adolescent parents.

The work values of black unwed adolescent parents were explored using the Values Scale. On 21 scales, the scores of 47 youth (12 to 20 years old) were compared with those of a preliminary normative sample presented in the test manual. Significant differences between the two groups were found on 16 of the 21 scales. The values of these black adolescent parents were less crystallized than were those of the normative group and reflect the concern for this group's satisfaction of their basic needs in which physical, safety, and self-esteem needs appeared most dominant.

Genetic organization and regulation of the xylose degradation genes in Streptomyces rubiginosus.

The xylose isomerase (xylA) and the xylulose kinase (xylB) genes from Streptomyces rubiginosus were isolated, and their nucleotide sequences were determined. The xylA and xylB genes encode proteins of 388 and 481 amino acids, respectively. These two genes are transcribed divergently from within a 114-nucleotide sequence separating the coding regions. Regulation of the xyl genes in S. rubiginosus was examined by fusing their promoters to the Pseudomonas putida catechol dioxygenase gene and integrating the fusions into the minicircle integration site on the S. rubiginosus chromosome. The expression of catechol dioxygenase was then measured under a variety of conditions. The results indicated that transcription of the xyl genes was induced by D-xylose and repressed by glucose. Data from quantitative S1 mapping were consistent with this conclusion and suggested that xylA had one and xylB had two transcription initiation sites. The transcription initiation site of xylA was 40 bp upstream of the coding region. The two transcription initiation sites of xylB were 20 and 41 bp 5' of its translation initiation codon. Under control of appropriate regulatory elements, the cloned xyl genes are capable of complementing either Escherichia coli xylose isomerase- or xylulose kinase-deficient strains. The deduced amino acid sequence of the S. rubiginosus xylA protein is highly homologous to sequences of other microbial xylose isomerases.

Dimensions of self-concept of pregnant unwed teens.

The study examined the self-esteem of pregnant teens enrolled in a program designed to maximize their chances of completing school. The Culture Free Self-Esteem Inventory (Battle, 1981) and the Coopersmith (1981) Self-Esteem Inventory were completed by the teens. The mean score of the group on the Culture Free Total Self Scale was below average in comparison to the norm.

Alteration of amino-terminal codons of human granulocyte-colony-stimulating factor increases expression levels and allows efficient processing by methionine aminopeptidase in Escherichia coli.

We have improved the expression of recombinant human granulocyte-colony-stimulating factor (G-CSF), produced by either pL or trpP expression vectors in Escherichia coli, by altering the sequence at the 5' end of the G-CSF-coding region. Initial attempts to express G-CSF resulted in neither detectable G-CSF mRNA nor protein in the trpP system, and only G-CSF mRNA was detectable in the pL system. We modified both expression vectors to decrease the G + C content of the 5' end of the coding region without altering the predicted amino acid sequence. This resulted in expression of detectable G-CSF mRNA and protein in both systems. Expression reached 17% and 6.5% of the total soluble cellular protein in the pL and trpP expression systems, respectively. The N-terminal sequence of the recombinant G-CSF from the pL system was Met-Thr-Pro-Leu-Gly-Pro-. G-CSF isolated from several human cell lines (including the LD-1 cell line reported here), does not have an N-terminal methionyl residue. Deletion of the threonine codon at the beginning of the coding region for the mature G-CSF resulted in efficient removal of the N-terminal methionine residue during expression in E. coli.

Binding of 125I-labeled recombinant beta interferon (IFN-beta Ser17) to human cells.

We investigated the binding of 125I-labeled beta interferon (IFN-beta Ser17), a nonglycosylated recombinant human fibroblast interferon in which cysteine at position 17 is replaced by serine by site-specific mutagenesis. An optimized chloramine T radiolabeling method produced a highly labeled, fully active 125I-IFN suitable for these studies. Unlike the case with the chloramine T method, incorporation of a single mole of Bolton-Hunter reagent into a mole of IFN-beta Ser17 led to nearly complete loss of biological activity. 125I-IFN-beta Ser17, prepared by the chloramine T method, bound specifically to human lymphoblastoid cells (Daudi) with a dissociation constant of 0.24 nM. The number of binding sites per cell was 4,000. In competition assays, unlabeled beta interferons (native, recombinant IFN-beta Cys17, and various preparations of IFN-beta Ser17) equally displaced labeled IFN-beta Ser17 on Daudi cells. Recombinant IFN-alpha-1 displaced 125I-IFN-beta binding to Daudi cells less efficiently than did unlabeled native or recombinant beta interferon. However, at the concentrations tested, native gamma interferon showed no competition with 125I-IFN. Our results indicate that IFN-beta Ser17 and native IFN-beta posses similar binding properties.

Localization of 2',3'-cyclic nucleotide-3'-phosphohydrolase within the vertebrate retina.

Histochemical and immunochemical techniques are used to locate 2',3'-cyclic nucleotide-3'-phosphohydrolase (2',3'-cNMP-3'ase) within cells of the vertebrate retina. A new histochemical method is described which links the hydrolysis of 2',3'-cNADP to the formation of a reduced, insoluble tetrazolium formazan. Photoreceptors from fish, bovine, and rat retinas are stained by this procedure. The reaction is blocked by 2'-AMP, a known inhibitor of 2',3'-cNMP-3'ase. Rabbit antibodies prepared against 2',3'-cNMP-3'ase from bovine brain are found to cross-react with bovine and rat retinal enzymes. Peroxidase-labeled antibody shows by light microscopy the greatest staining along the inner segments of the photoreceptors. Electron microscopy of the same preparations confirms binding to the plasma membrane of the inner segments of both rods and cones. Retinal 2',3'-cNMP-3'ase is thus predominantly associated with the photoreceptors, suggesting some role for 2',3'-cyclic nucleotides as substrates in visual function.

Comparison of 2',3'-cyclic nucleotide 3'-phosphodiesterase and the major component of Wolfgram protein W1.

Wolfgram protein preparations from myelin are heterogeneous mixtures having major components with molecular weights in the 43,000 to 60,000 range. Through the use of an SDS-slab gel electrophoretic system of high resolving power, the Wolfgram 1 (W1) component described by Nussbaum et al. (1977) has been resolved into two components; bovine W1a and W1b proteins are found to have mobilities identical to those of the two 2',3'-cyclic nucleotide 3'-phosphodiesterase (2'3'-CN 3'-ase) components, CNa and CNb (Drummond, 1979). Crossed immunoelectrophoresis with bovine 2',3'-CN 3'-ase demonstrates that CNa and CNb are antigenically indistinguishable. Rat and bovine Wolfgram proteins W1a and W1b, but not the W2 proteins, display cross reactivity with antiserum directed against bovine 2',3'-CN 3'-ase. Chymotryptic and Staphylococcus aureus V8 protease peptide profiles indicate structural similarities between proteins CNa-W1a and CNb-W1b. It is concluded that an inactivated form of 2',3'-Cn 3'-ase is a major component of Wolfgram protein W1. These results are consistent with the studies on the histochemical localization of rat W1 protein by Roussel et al. (1977, 1978).