Analysis of pathological complete response rates with paclitaxel-based regimens in trimodality therapy for esophageal cancer.

The study aimed to examine whether omission of 5-fluorouracil (5-FU)-containing chemotherapy alters pathological complete response rates in patients receiving trimodality therapy for locally advanced esophageal cancer. A total of 159 patients were identified. One hundred twenty-nine patients received platinum/5-FU concurrently with radiotherapy, and 30 received taxane/platinum-containing chemoradiotherapy prior to esophagectomy. Patients were staged using the 2002 American Joint Committee on Cancer staging system. Patients were matched between chemotherapeutic groups, with no significant demographic or clinical differences other than T stage (14% T2 in the 5-FU group; no T2 in the platinum/taxane group) and radiotherapy technique (8.5% received intensity-modulated radiotherapy in the 5-FU group; 60% in the platinum/taxane group). Pathological complete response rates for 5-FU and platinum/taxane-based groups were not significantly different (45% and 30%, respectively; P = 0.1548). Five-year overall survival and progression-free survival were not statistically different between the two groups. Significant predictors of pathological complete response included N stage (56% N0 and 33% N1; P = 0.0083), histology (37% adenocarcinoma and 59% squamous cell; P = 0.0123), tumor location (39% distal and 59% proximal/mid; P = 0.048), gastroesophageal junction involvement (33% involved and 55% uninvolved; P = 0.005), and radiotherapy end-to-surgery interval (50% < 55 days and 34% ≥ 55 days; P = 0.04). Grades 3-4 hematological toxicity was higher in the 5-FU group (36%) than in the paclitaxel-containing therapy group (17%; P = 0.0484). Use of paclitaxel-containing chemoradiotherapy did not result in inferior pathological complete response, overall survival, or progression-free survival rates, and resulted in less hematological toxicity than 5-FU treatment.

The Effect of Body Mass Index and Residence in Food Priority Areas on Patterns-of-Care and Cancer Outcomes in Patients With Stage III Non-Small Cell Lung Cancer.

PURPOSE: Patients living in food priority areas (FPAs), where access to healthy meals is challenging, may be at greater risk of nutritional deficits, leading to poorer cancer outcomes. Currently, there are no published data analyzing how FPAs affect patterns-of-care or outcomes for patients with locally advanced non-small cell lung cancer (NSCLC). We aimed to analyze the effect of residing in an FPA on treatments rendered and cancer outcomes in patients with stage III NSCLC treated at a single institution. METHODS AND MATERIALS: This is a retrospective study of 573 patients with locally advanced NSCLC consecutively treated from January 2000 to January 2020. χ2 and Mann-Whitney U tests were performed to determine differences between select variables. Kaplan-Meier analysis and Cox proportional hazard models were used to analyze overall survival (OS) and freedom from recurrence. Cox regression with forward model selection was used for multivariate analysis. RESULTS: Thirty-two percent of patients resided in an FPA (n = 183) and were more likely to self-identify as Black (P < .0001), single (P < .001), <60 years of age (P = .001), and uninsured (P < .0001), with a lower median income (P < .001). Patients in FPAs also had lower mean pre-chemoradiation (CRT) albumin (P = .002), lower pre-CRT body mass index (BMI) (P = .026), and were less likely to receive trimodality therapy (P ≤ .001) compared with patients not living in FPAs. There was no difference in OS or freedom from recurrence between the 2 cohorts. However, in patients with a normal BMI, either pre-CRT (median OS, 18.4 vs 25.0 months; P = .005) or after CRT (15.1 vs 28.1 months, P = .002), residing in an FPA resulted in an OS detriment. CONCLUSIONS: We demonstrated a clear socioeconomic divide in our patient population with stage III NSCLC, where residing in FPAs was associated with less-aggressive therapy and an OS detriment for patients with a normal-weight BMI. We are currently conducting a prospective study characterizing the nutritional needs of patients, particularly those who live in FPAs.

Cytokinin from soluble RNA of Escherichia coli: 6-(3-methyl-2-butenylamino)-2-methylthio-9-beta-D-ribofuranosylpurine.

We have isolated a compound responsible for the cytokinin activity of soluble RNA from Escherichia coli. The structure, indicated as 6-(3-methyl-2-butenylamino)-2-methylthio-9-beta-D-ribofuranosylpurine, C(16)H(23)N(5)0(4)S, on the basis of low-and high-reso!ution mass spectrometry, was established by unequivocal synthesis. The mass spectra, chromatographic behavior, and ultraviolet spectra of the compounds from natural and synthetic sources were identical.

Cytokinin of wheat germ transfer RNA: 6-(4-hydroxy-3-methyl-2-butenylamino)-2-methylthio-9-beta-D-ribofuranosylpurine.

A new modified nucleoside is responsible, in part, for the cytokinin activity of transfer RNA from wheat germ. The structure as judged by mass spec-trometry is 6-(4-hydroxy-3-methyl-2-butenylamino)-2-methylthio-9-beta-D-ribofuran-osylpurine. Unequivocal synthesis afforded material having ultraviolet, mass spectral, and chromatographic properties identical with those of the natural product.

Biological warfare agents as threats to potable water.

Nearly all known biological warfare agents are intended for aerosol application. Although less effective as potable water threats, many are potentially capable of inflicting heavy casualties when ingested. Significant loss of mission capability can be anticipated even when complete recovery is possible. Properly maintained field army water purification equipment can counter this threat, but personnel responsible for the operation and maintenance of the equipment may be most at risk of exposure. Municipal water treatment facilities would be measurably less effective. Some replicating (infectious) agents and a few biotoxins are inactivated by chlorine disinfection; for others chlorine is ineffective or of unknown efficacy. This report assesses the state of our knowledge of agents as potable water threats and contemplates the consequences of intentional or collateral contamination of potable water supplies by 18 replicating agents and 9 biotoxins known or likely to be weaponized or otherwise used as threats.

Diagnosis, stage, and prognosis of lung carcinoma by preoperative assay of lung tumor antigen-sensitive T lymphocytes.

Levels of circulating T lymphocytes sensitized to human lung tumor--associated antigens (LTA) were determined by the antigen-stimulated active rosette-forming T cell (AgARFC) assay. These levels were correlated with detection, pathological tumor stage, and postassay survival of patients with lung carcinoma. Peripheral blood lymphocytes (PBLs), from patients found to have lung cancer, were incubated with LTA and produced increased AgARFC compared to PBLs incubated without LTA. Significant levels of LTA-sensitive T cells were found in preoperative PBLs of 80% of patients with Stage I disease (8/10, p < 0.0005), 60% of those with Stage II disease (3/5, p < 0.025), and 46% of those with Stage III primary lung cancer (12/26, p < 0.01), compared with 11% of patients with either benign lung lesions (2/12) or lung metastases (0/6) of nonpulmonary malignant tumors (by chi square analysis). Postoperative survival correlated significantly with preoperative levels of LTA-sensitive T cells by AgARFC assay within Stage I lung cancer (r = 0.807, p < 0.0005). Stage I + II (r = 0.689, p < 0.001), and Stage III (r = 0.657, p < 0.001, not treated with chemotherapy). Preoperative PBL from patients with Stage I + II lung cancer were more frequently sensitized to LTA in the AgARFC assay than from patients with nonpulmonary carcinomas (0/22) or cigarette smokers (1/7) without pulmonary lesions (p < 0.0005). These findings demonstrate a high rate of detection of early, resectable lung carcinomas by preoperative AgARFC assay of PBL sensitized to LTA, and a significant correlation of LTA-sensitive T cell levels with tumor stage and patient survival. The AgARFC assay may be of prognostic as well as diagnostic value in the evaluation of patients with lung carcinoma.

Cell-mediated immunity to donor antigens in renal allograft recipients.

The antigen-stimulated active rosette-forming T-cell (AgARFC) assay was adapted for the preoperative study of 21 consecutive kidney transplants (17 cadaver donors and four living related donors; five retransplants). Recipient peripheral blood lymphocytes were incubated for 15 minutes with donor histocompatibility antigens preparaed by sonication of donor peripheral blood or splenic lymphocytes. Recipient presensitization to donor antigens was expressed as the difference between active rosette formation in the presence (%AgARFC) and in the absence (%ARFC) of donor antigens. This antigen-induced difference is rosette formation (%AgARFC - %ARFC) for all patients ranged from - 7.0% to 24.2%. Of those patients with pretransplant sensitization greater than 6.3% (group I: mean, 13.2 +/- 3.0; n = 7), 71% had severe acute rejection requiring dialysis within the first 2 weeks of transplantation. In contrast, none of the patients with pretransplant values below 6.3% (group II: mean, -0.8 +/- 1.0; n = 14) had rejection requiring dialysis within the first 2 weeks. Group I patients had 43% graft survival at 1 month and 14% survival at 2 months, whereas group II had 86% graft survival at 1 month and 71% at 2 months. The AgARFC assay provided a rapid means of measuring recipient T-cell presensitization to donor alloantigens, which was correlated with the accelerated rejection of renal allografts.

Inhibition of induction of human contact sensitization by topical glucocorticosteroids.

Ten healthy human volunteers were exposed to a primary sensitizing dose of 1 mg dinitrochlorobenzene (DNCB) by an open topical technique within an area that had been pretreated with a potent topical glucocorticosteroid compound. Quantitative elicitation testing was performed on the opposite side by an open patch test technique two weeks after the sensitizing application. One (10%) of the ten subjects became sensitized. A matched control group of ten subjects was similarly sensitized without steroid treatment. Eight (80%) of the ten became sensitized. One month later, five of the eight test subjects in whom sensitization had been prevented were retested in an identical fashion without steroid pretreatment, to determine if any degree of tolerance had been induced. All five subjects became sensitized. Topical glucocorticosteroids inhibited the development of sensitization to topically applied DNCB. Tolerance was not induced by this single process.

Warming fluid for amnioinfusion during labor.

While it has never been shown that warming fluid to body temperature prior to using it for amnioinfusion in labor is necessary, the practice is generally accepted. Ideally it is done with a blood warmer. Since blood warmers are expensive and not always available, fluid bags are often warmed in "constant temperature" devices used to heat blankets and fluid used in surgery. These units are ubiquitous, create no extra expense with their use and are a reasonable alternative to blood warmers. A study was designed to determine whether warming ovens actually did heat the fluids used for amnioinfusion to around 37 degrees C. Fluid bags were placed in the warming oven for 48 hours or more, and opening temperatures of the contained fluids were recorded. The temperatures were extremely variable, ranging from 21 degrees C to > 50 degrees C. The variability in opening temperatures was a result of wide temperature fluctuations in the warming oven itself and the condition of the fluid bags on removal. Blanket and surgical fluid warming ovens are not appropriate for heating fluids used in amnioinfusion during labor.

Safety and efficacy of early postoperative solid food consumption after cesarean section.

Traditionally patients have received a physician-dictated regimen of gradual expansion of their diets following cesarean section. This has been based upon concern about the possibility of ileus from expanding the diet too rapidly. Given the economic necessity of earlier postoperative discharge following abdominal delivery, many patients have solid food reintroduced in their diets around the time they leave the hospital. This prospective, randomized, controlled study compared a traditional, gradual dietary expansion scheme with patient-determined reintroduction of solid food, which was offered within eight hours of surgery. The hypotheses were that women would eat more rapidly after cesarean section when given the opportunity and that early solid food consumption would reduce the need for analgesia. The results indicated that both hypotheses were correct. Given the opportunity, women will eat solid food very soon after cesarean section (mean +/- SD 10.2 +/- 5.2 hours from surgery to onset of solid food consumption) as compared to women on a traditional dietary expansion regimen (mean +/- SD 41.5 +/- 16.0 hours, P < .001). Women offered food within hours of cesarean section required less patient-requested injectable narcotic postoperatively than did women on gradual dietary expansion (median, 75 mg versus 225 mg meperidine, P < .05). There was no evidence of compromise of safety or comfort from introducing solid food early and allowing the patient to decide when to eat postoperatively. The conclusion from these data is that early postoperative feeding after cesarean section is a safe and effective alternative for most women, who now face early hospital discharge.

The GPCR OGR1 (GPR68) mediates diverse signalling and contraction of airway smooth muscle in response to small reductions in extracellular pH.

BACKGROUND AND PURPOSE: Previous studies have linked a reduction in pH in airway, caused by either environmental factors, microaspiration of gastric acid or inflammation, with airway smooth muscle (ASM) contraction and increased airway resistance. Neural mechanisms have been shown to mediate airway contraction in response to reductions in airway pH to < 6.5; whether reduced extracellular pH (pHo) has direct effects on ASM is unknown. EXPERIMENTAL APPROACH: Intracellular signalling events stimulated by reduced pHo in human cultured ASM cells were examined by immunoblotting, phosphoinositide hydrolysis and calcium mobilization assays. ASM cell contractile state was examined using magnetic twisting cytometry. The expression of putative proton-sensing GPCRs in ASM was assessed by real-time PCR. The role of ovarian cancer G protein-coupled receptor 1 (OGR1 or GPR68) in acid-induced ASM signalling and contraction was assessed in cultures subjected to siRNA-mediated OGR1 knockdown. KEY RESULTS: ASM cells responded to incremental reductions in pHo (from pH 8.0 to pH 6.8) by activating multiple signalling pathways, involving p42/p44, PKB, PKA and calcium mobilization. Coincidently, ASM cells contracted in response to decreased pHo with similar 'dose'-dependence. Real-time PCR suggested OGR1 was the only proton-sensing GPCR expressed in ASM cells. Both acid-induced signalling (with the exception of PKB activation) and contraction were significantly attenuated by knockdown of OGR1. CONCLUSIONS AND IMPLICATIONS: These studies reveal OGR1 to be a physiologically relevant GPCR in ASM cells, capable of pleiotropic signalling and mediating contraction in response to small reductions in extracellular pH. Accordingly, ASM OGR1 may contribute to asthma pathology and represent a therapeutic target in obstructive lung diseases.

Mode of action of N,N'-diphenylurea: The isolation and identification of the cytokinins in the transfer RNA from tobacco callus grown in the presence of N,N'-diphenylurea.

The tRNA from cytokinin-dependent tobacco callus (Nicotiana tabacum) grown on mineral medium containing N,N'-diphenylurea as the source of cytokinin was found to contain 3 cytokinin-active ribonucleosides. The 2 ribonucleosides present in the largest amounts were identified conclusively by their chromatographic properties, ultra-violet and low-resolution mass spectra as the naturally-occurring cytokinins 6-(4-hydroxy-3-methyl-cis-2-butenylamino)-9-ß-D-ribofuranosylpurine and 6-(3-methyl-2-butenylamino)-9-ß-ribofuranosylpurine. A third ribonucleoside, present in smaller amounts, was identified as another naturally-occurring cytokinin 6-(4-hydroxy-3-methyl-2-butenylamino)-2-methylthio-9-ß-D-ribofuranosylpurine on the basis of its chromatographic behaviour. No evidence was found to associate the mode of action of the non-purine cytokinin, N,N'-diphenylurea, with tRNA.

Evidence in support of biosynthesis de novo of free cytokinins.

The four cytokinins in the tRNA from Lupinus luteus L. seeds have been purified and identified as ribosyl-cis-zeatin, 2-methylthio-ribosylzeatin, (Δ (2)-isopentenyl)adenosine and 2-methylthio-N(6)-(Δ (2)-isopentenyl)adenosine. These structures have been assigned on the basis of their chromatographic mobilities and the spectroscopic data of the parent materials and their silylated derivatives. The tRNA isolated from Populus x robusta Schneid. leaves contained four cytokinins with identical chromatographic properties to those identified in Lupinus luteus seed tRNA. No evidence was obtained for the presence, in tRNA, of the naturally occurring free cytokinins identified in these plant species, dihydrozeatin (Lupinus luteus) and N(6)-(2-hydroxybenzyl)adenosine (Populus x robusta). This is evidence in support of the possibility that free cytokinins can arise by biosynthesis de novo and are not exclusively by-products released intact during tRNA turnover.

Immunity to cholera: relation of fraction II of type 2 cholera toxin to vibriocidal antibody.

The nontoxic protein component in supernatant fluids of young cultures of the cholera vibrio in peptone dialysate broth contains an antigen identical in specificity to vibrio lipopolysaccharide. This material was heterogeneous after elution from diethylaminoethyl A50 Sephadex, and it contained at least five additional minor antigens. Identity was demonstrated by immunodiffusion methods, by the induction of specific vibriocidal antibody formation, and by specific interference in the vibriocidal reaction. The minor antigens appeared to be unrelated to the vibriocidal reaction. The major antigen was more highly immunogenic than lipopolysaccharide, giving higher and longer-persisting antibody titers in the rabbit, but lipopolysaccharide was the more effective interfering antigen per unit weight in the vibriocidal reaction. The nontoxicity and high immunogenic potency of the protein antigen suggest that it may be useful as an immunizing agent for the production of the antibacterial component of an effective immunity.