Long-term weight development after esophagectomy for cancer-comparison between open Ivor-Lewis and minimally invasive surgical approaches.

Esophagectomy is an extensive procedure with severe postoperative effects. It can be assumed that the greater the trauma, the longer the nutritional recovery. This retrospective observational single-center cohort study compared weight development after esophagectomy with open and minimally invasive techniques. Three groups were compared in this study, one representing the first 41 patients who underwent the minimally invasive McKeown esophagectomy (MIMK). The second group included the first 84 consecutive patients operated with the minimally invasive Ivor-Lewis esophagectomy (MIIL). The third group comprised 100 consecutive patients operated with open thoracoabdominal Ivor-Lewis esophagectomy (IL). Virtually all patients submitted to a minimally invasive esophagectomy (MIE) and the majority with an IL had a jejunal catheter inserted during operation for postoperative enteral feeding. All together 225 patients were included in this study. The mean weight loss during the first year was 13.1% (±4.1), 11.2% (±6.1), and 9.6% (±7.5) in the IL, MIIL, and MIMK group, respectively (P = 0.85 and P = 0.95, respectively). The median duration of postoperative enteral nutrition support varied substantially within the groups and was 23.5 days in the IL group (range: 0-2033 days), 54.5 days in those having an MIIL (range: 0-308 days; P ≤ 0.001) and 57.0 days among patients in the MIMK group (range: 0-538 days; P ≤ 0.022). There was no difference in the risk of losing at least 10% of the preoperative weight at 3 or 6 months postoperatively between the groups. However, in patients who suffered severe complications (Clavien-Dindo score ≥ IIIb) after MIIL, there was a nonsignificant trend toward a lower risk of a 10% or greater weight loss, 3 months postoperatively. In conclusion, the greater surgical trauma associated with the traditional open esophagectomy was not followed by more severe weight loss, or other signs of poorer nutritional recovery, when compared to minimal invasive surgical techniques.

Relief of dysphagia during neoadjuvant treatment for cancer of the esophagus or gastroesophageal junction.

Dysphagia is the main symptom of cancer of the esophagus and gastroesophageal junction and causing nutritional problems and weight loss, often counteracted by insertion of self-expandable metal stents or nutrition via an enteral route. Clinical observations indicate that neoadjuvant therapy may effectively and promptly alleviate dysphagia, making such nutrition supportive interventions redundant before surgical resection. The objective of the current study was to carefully study the effects of induction neoadjuvant therapy on dysphagia and its subsequent course and thereby investigate the actual need for alimentary gateways for nutritional support. Thirty-five consecutive patients scheduled for neoadjuvant therapy were recruited and assessed regarding dysphagia and appetite at baseline, after the first cycle of preoperative treatment with either chemotherapy alone or with chemoradiotherapy and before surgery. Platinum-based therapy in combination with 5-fluorouracil was administered intravenously days 1-5 every 3 weeks and consisted of three treatments. Patients receiving combined chemoradiotherapy started radiotherapy on day one of second chemotherapy cycle. They received fractions of 2 Gy/day each up to a total dose of 40 Gy. Watson and Ogilvie dysphagia scores were used to assess dysphagia, while appetite was assessed by the Edmonton Assessment System Visual analogue scale-appetite questionnaire. Patients were evaluated at regular outpatient clinic visits or by telephone. The histological tumor response in the surgical specimen was assessed using the Chirieac scale. Ten patients scheduled for neoadjuvant chemotherapy and 25 patients scheduled for chemoradiotherapy were included in the analysis. There was a significant improvement in dysphagia in both treatment groups, according to both scales, already from baseline to the completion of the first chemotherapy cycle which remained to the end of the neoadjuvant treatment (P < 0.001). Appetite also improved after the first chemotherapy cycle (P = 0.03). Body weight did not change during any type of neoadjuvant therapy. We were unable to demonstrate any association between relief of dysphagia and the degree of histological response to neoadjuvant therapy in the surgical specimen. The present study shows that a platin - 5FU-based neoadjuvant chemotherapy, with or without concomitant radiotherapy, effectively and promptly relieves dysphagia in patients presenting with cancers of the esophagus or gastroesophageal junction already after the first cycle.

Influence of natural exposure on castor oil based polyurethane reinforced with waste tire rubber.

Waste tire rubber (WTR) has been extensively generated worldwide due to mobility needs growth. About 1.5 billion units are generated annually, constantly discharged in the environment with a few reusability alternatives. Therefore, rubber recovery methods and these residues' transformation into a cost-effective product have gained attention. Aiming to minimize the usage of fossil resources and contributes to a circular economy, it was analyzed the usage of WTR particles (5-20% by weight) in castor oil-based polyurethane foams under natural aging to promote a holistic view of all factors involved in the performance of the foams. Morphological, thermal, chemical, and mechanical properties were determined before and after exposure to open air to observe the impact of photo-oxidation and hydrolysis. The increase in viscosity of pre-polymer during the rubber loading produced greater density foams with smaller cell sizes than neat PU, in which the average cell size increased after the weathering. The rubber contributes to enhancing the compressive behavior in the non-exposed samples. After exposure, the results suggest that degradation may act to increase the crosslinking density even with the presented structural changes such as yellowing and voids. Regarding thermal stability, the rubber promotes a slight decay in the ability to resist a heat flow before and after weathering. Still, the char yield increased, showing a possibility of better fire retardancy for composites. FTIR and UV-vis showed chemical structure changes as Photo-Fries network rearrangement, Norrish I random chain scission, and Norrish II ß-scission. Besides, UV-vis revealed the maximum absorbance in the UVB region, showing that the PU reinforced by WTR can be a promising material for civil coatings.

Early stages of motor neuron differentiation revealed by expression of homeobox gene Islet-1.

Motor neurons in the embryonic chick spinal cord express a homeobox gene, Islet-1, soon after their final mitotic division and before the appearance of other differentiated motor neuron properties. The expression of Islet-1 by neural cells is regulated by inductive signals from the floor plate and notochord. These results establish Islet-1 as the earliest marker of developing motor neurons. The molecular nature of the Islet-1 protein suggests that it may be involved in the establishment of motor neuron fate.

The homeodomain LIM protein Isl-1 is expressed in subsets of neurons and endocrine cells in the adult rat.

We have used immunocytochemical methods to localize the homeodomain LIM protein Isl-1 in the adult rat. Isl-1 immunoreactivity is expressed in polypeptide hormone-producing cells of the endocrine system, in neurons of the peripheral nervous system, and in a subset of brain nuclei. Isl-1 is also expressed in a subset of motoneurons in the spinal cord and brain stem, but not in regions of the central nervous system involved in sensory function or in neocortical areas. The pattern of expression of Isl-1 suggests that this gene may be involved in the specification and maintenance of differentiated phenotypical properties of these cells.

Different levels of repressor activity assign redundant and specific roles to Nkx6 genes in motor neuron and interneuron specification.

Specification of neuronal fate in the vertebrate central nervous system depends on the profile of transcription factor expression by neural progenitor cells, but the precise roles of such factors in neurogenesis remain poorly characterized. Two closely related transcriptional repressors, Nkx6.2 and Nkx6.1, are expressed by progenitors in overlapping domains of the ventral spinal cord. We provide genetic evidence that differences in the level of repressor activity of these homeodomain proteins underlies the diversification of interneuron subtypes, and provides a fail-safe mechanism during motor neuron generation. A reduction in Nkx6 activity further permits V0 neurons to be generated from progenitors that lack homeodomain proteins normally required for their generation, providing direct evidence for a model in which progenitor homeodomain proteins direct specific cell fates by actively suppressing the expression of transcription factors that direct alternative fates.

Specification of neuronal fates in the ventral neural tube.

The generation of distinct classes of neurons at defined positions is a fundamental step in the development of the vertebrate central nervous system. Recent work has begun to reveal the extracellular signals and transcriptional mediators that direct the pattern of generation of distinct neuronal subtypes in the neural tube. This work has provided a framework to understand the patterning of the ventral neural tube and is permitting molecular analyses of the assembly of functional neuronal circuits.

Role of tRNA modification in translational fidelity.

In transfer RNA many different modified nucleosides are found, especially in the anticodon region. In this region, pseudouridine (psi) is found in positions 38, 39 or 40 in a subset of tRNA species, 2-methylthio-6-hydroxyisopentenyladenosine (ms2io6A) is found in position 37 in tRNAs that read codons starting with U and 1-methylguanosine (m1G) is found in position 37 in tRNAs reading codons of the UCCNG type. We have used the mutants hisT, miaA and miaB and trmD, which are deficient in the biosynthesis of psi, ms2io6A, and m1G, respectively, to study the functional aspects of the respective modified nucleosides. We have shown: (1) Presence of psi improved the cellular growth rate, the polypeptide step-time, and the efficiency of an amber suppressor, but did not appreciably sense the codon context. (2) Presence of ms2io6A improved the cellular growth rate, the polypeptide step-time and the efficiency of several amber suppressor tRNAs. It also had a profound effect on the codon context sensitivity of the tRNA. (3) Presence of m1G improved the cellular growth rate and the polypeptide steptime and also prevented the tRNA from shifting the reading frame. Thus, these three modified nucleosides present in the anticodon region have apparently different functions.

tRNA anticodons with the modified nucleoside 2-methylthio-N6-(4-hydroxyisopentenyl)adenosine distinguish between bases 3' of the codon.

The modified nucleoside 2-methylthio-N6-(4-hydroxyisopentenyl)adenosine (ms2io6A) is present immediately to the 3' side of the anticodon (position 37) in tRNAs that read codons starting with uridine and hence include amber (UAG) suppressor tRNAs. We have used strains of Salmonella typhimurium that differ only in their ability to synthesize ms2io6A in order to determine specifically how this modified nucleoside influences the efficiency of amber suppression in two codon contexts differing by only which base is 3' of the codon. The results show that the presence of the modified nucleoside ms2io6A not only improves the efficiency of the suppressor tRNAs but also allows them to distinguish between at least two bases 3' of the codon. Thus, the presence of ms2io6A reduces the intrinsic codon context sensitivity of the tRNA and specifically counteracts an unfavourable nucleotide on the 3' side of the codon. The possible codon-anticodon interactions responsible for this effect are discussed.

Genomic sequence and embryonic expression of the zebrafish homeobox gene hox-3.4.

We have analyzed the genomic DNA sequence and embryonic expression pattern of the zebrafish hox-3.4 gene. Two exons, encoding a protein with a total size of 232 amino acids, were identified within a 3.5 kbp genomic region. Besides the homeodomain, which is identical to that of the human HOX3D and mouse Hox-3.4 genes, the first 58 residues of the N-terminal domain in the predicted Hox-3.4 protein share 48% sequence identity with the gene product of the human cognate. Some of the N-terminal sequence elements are also conserved relative to the two other members of the Hox-1.3/Hox-2.1/Hox-3.4 paralogy group. In addition, the paralogous genes share a significant degree of sequence identity in non-coding regions. This conservation is particularly evident in the promoter regions of the cognates hox-3.4, Hox-3.4, and HOX3D, where a 180 bp TATA-box-containing element with a 60% identity is located. This is in agreement with the previous finding that the HOX3D promoter region contains response elements for other Hox proteins and retinoids. Also with respect to embryonic expression, the zebrafish hox-3.4 gene is very similar to its mammalian counterparts. Within the central nervous system of 16, 24, and 48 h embryos, hox-3.4 transcripts were detected throughout most of the spinal cord from a boundary at the posterior end of the hindbrain. In 16 h embryos the hox-3.4 gene is also active within a restricted region of the tailbud.

Sonic hedgehog: a common signal for ventral patterning along the rostrocaudal axis of the neural tube.

The vertebrate hedgehog-related gene, sonic hedgehog, is expressed in ventral domains along the entire rostrocaudal length of the neural tube, including the forebrain. Shh induces the differentiation of ventral neuronal cell types in explants derived from prospective forebrain regions of the neural plate. Neurons induced in explants derived from diencephalic and telencephalic levels of the neural plate express the LIM homeodomain protein Islet-1, but these neurons possess distinct identities that match those of the ventral neurons normally generated in these two subdivisions of the forebrain. These results, together with other studies of neuronal differentiation at caudal levels of the neural tube, suggest that a single inducing molecule, Shh, mediates the induction of distinct ventral neuronal cell types along the entire rostrocaudal extent of the embryonic central nervous system.

Cloning and DNA-binding properties of the rat pancreatic beta-cell-specific factor Nkx6.1.

The homeodomain (HD) protein Nkx6.1 is the most beta-cell-specific transcription factor known in the pancreas and its function is critical for the formation of the insulin-producing beta-cells. However, the target genes, DNA-binding site, and transcriptional properties of Nkx6.1 are unknown. Using in vitro binding site selection we have identified the DNA sequence of the Nkx6.1 binding site to be TTAATTG/A. A reporter plasmid containing four copies of this sequence is activated by an Nkx6.1HD/VP16 fusion construct. Full-length Nkx6.1 fails to activate this reporter plasmid in spite of robust interaction with the binding site in vitro. Stable expression of Nkx6.1 in the glucagon-producing alpha-cell-like MSL-G-AN cells induces expression of the endogenous insulin gene in a subset of the cell population. The expression of other known beta-cell-specific factors such as Pax4, Pax6, Pdx1, GLUT2 and GLP1-R is unchanged by the introduction of Nkx6.1.

Pharmacokinetics and pharmacodynamics of intravenous ciprofloxacin. Studies in vivo and in an in vitro dynamic model.

The pharmacokinetics and pharmacodynamics of a 200-mg intravenous dose of ciprofloxacin were studied in normal volunteers and in an in vitro dynamic model that exposes bacteria to changing concentrations of the drug in a neutropenic setting. Peak ciprofloxacin concentrations in vivo averaged 3.2 micrograms/ml. The terminal serum elimination half-life averaged 4.2 hours. The volume of distribution of ciprofloxacin was large and consistent with extensive extravascular distribution. Slightly less than half of the dose was recovered unchanged in urine by 48 hours after infusion. The median serum bactericidal titer against a strain of Escherichia coli was 1:16 or more for at least six hours after infusion, but was only 1:2 against a strain of Pseudomonas aeruginosa immediately after the end of the infusion. Pharmacodynamic studies in the in vitro model with a simulated regimen of 200 mg administered intravenously every 12 hours demonstrated rapid and complete killing of this strain of E. coli following the first 200-mg "dose." For the strain of P. aeruginosa, an initial bactericidal effect was observed due to the eradication of susceptible subpopulations of bacteria; however, regrowth of resistant organisms was observed. These data suggest that a regimen of 200 mg administered intravenously every 12 hours results in rapid killing of susceptible bacteria. Higher doses or combination therapy may be required to prevent the emergence of resistant P. aeruginosa in this model and in the setting of neutropenia.

Skeletal concentrations of lead, cadmium, zinc, and silver in ancient North American Pecos Indians.

Bone samples of 14 prehistoric North American Pecos Indians from circa 1400 A.D. were analyzed for lead, cadmium, zinc, and silver by graphite furnace atomic absorption spectrometry to establish the baseline levels of these elements in an ancient North American population. Measurements of outer and inner bone fractions indicate the former were contaminated postmortem for lead, zinc, and cadmium. The contamination-adjusted average (mean +/- SD) level of lead (expressed as the ratio of atomic lead to atomic calcium) in bones of the Indians was 8.4 +/- 4.4 x 10(-7)), which was similar to ratios in bones of ancient Peruvians (0.9 to 7.7 x 10(-7)) and significantly lower than ratios in bones of modern adults in England and the United States (210 to 350 x 10(-7]. The adjusted average concentrations (microgram per gram dry weight) of biologic cadmium, silver, and zinc in the Pecos Indian bones were 0.032 +/- 0.013, 0.094 +/- 0.044, and 130 +/- 66, as compared to concentrations of 1.8, 0.01 to 0.44, and 75 to 170 in the bones of modern people, respectively. Therefore, cadmium concentrations in Pecos Indian bones are also approximately 50-fold lower than those of contemporary humans. These data support earlier findings that most previously reported natural concentrations of lead in human tissues are erroneously high and indicate that natural concentrations of cadmium are also between one and two orders of magnitude lower than contemporary concentrations.

Lead in ancient human bones and its relevance to historical developments of social problems with lead.

Concentrations of metabolic lead in buried ancient bones are obscured by replacement of calcium in apatite by excessive amounts of soil moisture Pb. Concentrations of metabolic barium in bones are affected in a similar way. Added soil Pb and Ba, expressed as log(Pb/Ca) versus log(Ba/Ca) among various bones at a given burial site, are positively covariant, with about 5-fold more soil Pb added for each unit of added soil Ba. The typical natural metabolic Ba/Ca ratio in contemporary people can be measured unambiguously because it as unaffected by industrial pollution. It applies to ancient people because it has not changed historically. The intercept of the covariance curve for buried bones of a given ancient population at the known metabolic Ba/Ca ratio indexes the corresponding metabolic Pb/Ca ratio in bones of that population. Lead levels which prevailed in Romans appear to have been similar to those in contemporary people, which are approximately 1000-fold above natural levels in humans determined by this method in ancient Peruvians. This indicates that studies of natural biochemical reactions in cells free of industrial Pb should be made, because most present biochemical knowledge is founded on data obtained from systems polluted with Pb 1000 to 100000-fold above natural levels. The 5000 year history of smelting Pb by humans indicates that a system of education fostered by genetically common lower brain center functions operated on hundreds of successive generations in a context of cultural changes invoked by feedback from developments in engineering technologies to give rise to the difference between present typical and prehistoric natural levels of Pb in humans. Archaeological and anthropological studies of early developments in writing, music and metallurgy by ancient Peruvians and Persian peoples should be combined with PET-scan studies of their descendants to discover if, as preliminary archaeological data suggest, the two ancient populations differed on a genetic basis in higher brain functions, yet are indistinguishable as metallurgical engineers. This would demonstrate that higher centers of the human brain did not exercise guiding control, through hundreds of generations, over those developments of engineering technologies which resulted in the extreme pollution of the earth's biosphere with poisonous Pb.

Natural skeletal levels of lead in Homo sapiens sapiens uncontaminated by technological lead.

Lead, Ba and Ca concentrations were determined in tooth enamel, femur and rib from buried skeletons of PreColumbian Southwest American Indians, 10 subjects who lived 1000 years ago on the Pacific coast at 34 degrees N, and 13 subjects who lived 700 years ago in a desert valley tributary of the Colorado River at 37 degrees N 111 degrees W, both groups living in environments uncontaminated by technological Pb. For the coastal tribe, average Pb/Ca ratios were 1.1 x 10(-7) in enamel, 2.3 x 10(-7) in femur and 4.7 x 10(-7) in rib, while Ba/Ca ratios were 1.2 x 10(-5) in enamel, 32 x 10(-5) in femur and 38 x 10(-5) in rib (wt ratios). For the desert tribe, average Pb/Ca ratios were 4 x 10(-7) in enamel, 11 x 10(-7) in femur and 37 x 10(-7) in rib, while Ba/Ca ratios were 1.1 x 10(-5) in enamel, 7.5 x 10(-5) in femur and 6.2 x 10(-5) in rib. It is shown that biologic levels of Pb and Ba in buried femur and rib at both burial sites and in buried enamel at the Arizona site are obscured by excessive diagenetic additions of Pb and Ba from soil moisture. It is shown that one-third of the Pb in enamel at the Malibu site is biologic, yielding a skeletal Pb/Ca (wt) ratio of 4 x 10(-8). This is equivalent to a mean skeletal concentration of 13 ng Pb g-1 bone ash, and a mean natural body burden of 40 micrograms Pb/70 kg adult Homo sapiens sapiens, uncontaminated by technological Pb. This value is about one-thousandth of the mean body burden of 40 mg industrial Pb/70 kg adult American today, which indicates the probable existence within most Americans of dysfunctions caused by poisoning from chronic, excessive overexposures to industrial Pb.

Determination of semduramicin sodium in poultry liver by liquid chromatography with vanillin postcolumn derivatization.

A liquid chromatographic (LC) method is described for the quantitative determination of semduramicin sodium in broiler liver when administered under projected use conditions. For this procedure, semduramicin sodium is extracted from liver with methanolic ammonium hydroxide, separated and concentrated by solid-phase extraction steps, and determined by LC with postcolumn derivatization with vanillin. The mean recovery of drug was 95% over the 40-320 ng/g range, the coefficient of variation was +/- 10% or better, and no interference was observed from commercial polyether ionophores. The minimum level of detection for semduramicin sodium in broiler liver is 25 ng/g.

Large-diameter (30-35 mm) pneumatic balloon dilatation of the pylorus in patients with gastric outlet obstruction symptoms after esophagectomy.

BACKGROUND AND AIMS: Functional gastric outlet obstruction is a common problem after esophagectomy. The aim of this study was to evaluate the safety and efficacy of treating this group of patients with pneumatic dilatation of the pyloric sphincter region using a large-diameter (30-35 mm) balloon. MATERIAL AND METHODS: A review of all patients who had undergone pneumatic dilatation of the pylorus sphincter because of gastric outlet obstruction symptoms after esophagectomy at the Karolinska University Hospital from 2006-2011 was completed. Main outcomes were recordings of nausea, regurgitation and bloating. RESULTS: A total of 13 patients received pneumatic dilatation after an esophagectomy. The median time between esophagectomy and the first dilatation was 100 days, and the patients underwent a total of 21 dilatations (1-3 per patient) to a final median diameter of 30 mm. No procedure-related complications occurred. The median follow-up time was 205 days, and nausea and regurgitation improved significantly (p < 0.001, Fisher's test). CONCLUSIONS: Pneumatic dilatation of the pylorus using a large-diameter pneumatic balloon seems to be a safe and effective method for treating symptoms suggestive of gastric outlet obstruction after esophagectomy. To document its true effectiveness, a randomized and sham-controlled study is needed.

The influence of cone-beam computed tomography and periapical radiographic evaluation on the assessment of periapical bone destruction in dog's teeth.

OBJECTIVE: The aim of this study was to determine the influence of periapical radiographs, cone beam computed tomography (CBCT) sections, and cone beam volumetric data on the determination of periapical bone destruction in endodontically treated distal root canals of premolar canine teeth. Nontreated mesial roots were used as controls. STUDY DESIGN: Enterococcus faecalis strain (ATCC 29212) was inoculated into 30 root canals of 2 mongrel dogs to induce apical periodontitis. After 60 days, the root canals of the distal roots of the 11 mandibular and 4 maxillary premolars were endodontically treated (n = 15). The mesial root canals were used as controls (no treatment). The bone destruction was evaluated after 6 months by 5 evaluators using periapical radiographs and by CBCT (coronal and sagittal sections). After the experimental period, the area of the lesions in periapical radiographs and CBCT sections were measured in mm(2) using the ImageTool software. A single evaluator measured the volumetric data using the OsiriX software. The comparison between the diagnosis methods in treated root canals and controls was performed using parametric and nonparametric criteria. The Pearson correlation coefficient was computed between radiographic values and CBCT volumetric data in treated root canals and controls. RESULTS: The results showed the presence of chronic apical periodontitis in every inoculated tooth. After 6 months, periapical radiographs, coronal CBCT sections, and volumetric data showed lower bone destruction in endodontically treated teeth in comparison with the control group (P < .05). The 5 evaluators found no differences between the apical periodontitis area of treated teeth and controls when CBCT sagittal sections were used (P > .05). No correlation was found between x-ray and CBCT volumetric values in treated root canals. CONCLUSIONS: Although selected CBCT sagittal sections showed similar values of bone destruction in endodontically and nontreated root canals, volumetric CBCT data showed that periapical lesions of endodontically treated root canals had half of the volume of periapical lesions in nontreated root canals. No relationship could be found between the periapical values of bone destruction and volumetric data found in CBCT of treated rood canals.