bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonsteroidal Anti-Inflammatory Drugs, Alone or Combined With Opioids, for Cancer Pain
Authors: McNicol Ewan , Strassels Scott , Goudas Leonidas , Lau Joseph , Carr Daniel 
Published: May 2004

PurposeTo assess the safety and efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs), alone or combined with opioids, for the treatment of cancer pain.Patients and MethodsForty-two trials involving 3,084 patients met inclusion criteria: eight compared NSAID with placebo; 13 compared one NSAID with another; 23 compared NSAID with opioid, NSAID or opioid versus NSAID plus opioid combinations, or NSAID plus opioid combinations versus NSAID plus opioid combinations; and nine studies assessed the effect of increasing NSAID dose.ResultsSixteen studies lasted 1 week or longer and 11 evaluated a single dose. Seven of eight trials demonstrated superior efficacy of single doses of NSAID compared with placebo. Only four of 13 studies reported increased efficacy of one NSAID compared with another; four other studies found that one NSAID had fewer side effects than one or more others. Thirteen of 14 studies found no difference, or minimal clinical difference, when comparing an NSAID plus opioid combination versus either drug alone. Comparisons between various NSAID plus opioid combinations were inconclusive. Four studies demonstrated increased efficacy with increased NSAID dose, without dose-dependent increases in side effects.ConclusionHeterogeneity of study methods and outcomes precluded meta-analyses. Short duration of studies undermines generalization of findings on efficacy and safety. On the basis of limited data, NSAIDs appear to be more effective than placebo for cancer pain; clear evidence to support superior safety or efficacy of one NSAID compared with another is lacking; and trials of combinations of an NSAID with an opioid have disclosed either no significant difference, or at most a slight but statistically significant advantage, compared with either single entity.
RRM1 and PTEN As Prognostic Parameters for Overall and Disease-Free Survival in Patients With Non–Small-Cell Lung Cancer
Authors: Bepler Gerold , Sharma Swati , Cantor Alan , Gautam Ashish , Haura Eric , Simon George , Sharma Anupama , Sommers Eric , Robinson Lary 
Published: May 2004

Purpose RRM1 has important functions in the determination of the malignant phenotype. It controls cell proliferation through deoxynucleotide production and metastatic propensity through PTEN induction. It is located in a region of loss of heterozygosity in non–small-cell lung cancer (NSCLC), which is a predictor of poor survival. We hypothesized that RRM1 expression would be a significant predictor of outcome in NSCLC. Patients and Methods A retrospective data set of 49 patients and a prospective data set of 77 patients with resectable NSCLC were studied. RNA was extracted from tumor and normal lung tissue, and expression of the genes RRM1, PTEN, and RRM2 was determined by real-time quantitative polymerase chain reaction. Results RRM1 expression was significantly correlated with PTEN and RRM2 expression in tumor tissue. RRM1 and PTEN expression in tumor tissue was highly predictive of overall (P = .011 and .018, respectively) and disease-free survival (P = .002 and .026, respectively). Patients with high levels of expression lived longer and had disease recurrence later than patients with low levels of RRM1 and PTEN. In a multivariate analysis, high RRM1 expression was predictive of long survival independent of tumor stage, performance status, and weight loss. Conclusion RRM1 is a biologically and clinically important determinant of malignant behavior in NSCLC. Knowing the level of expression of this gene adds significant information to management decisions independent of the currently used outcome predictors of tumor stage, performance status, and weight loss. Future clinical trials should stratify patients based on expression of this gene to avoid unwanted biases.
Dogmas and controversies in the handling of nitrogenous wastes: The effect of feeding and fasting on the excretion of ammonia, urea and other nitrogenous waste products in rainbow trout
Authors: Kajimura Makiko , Croke Sara J. , Glover Chris N. , Wood Chris M. 
Published: May 2004

SUMMARYAmmonia and urea are the primary forms of nitrogen excretion in teleost fish. There exists, however, a discrepancy between the sum of ammonia plus urea nitrogen and total nitrogen, indicating that `unknown' nitrogen end products may play an important role in nitrogen metabolism. The current study analysed a wide range of nitrogen end products in both fed and fasted juvenile rainbow trout. Ammonia-N (53–68%) and urea-N (6–10%) were confirmed as the most important forms of nitrogenous waste, but an interesting finding was the considerable excretion of nitrogen as amino acids(4–10%), via the gills, and as protein (3–11%), probably via the body mucus. Use of anal sutures delineated an important role for the gastrointestinal tract in the production of ammonia-N and urea-N in fed fish, but amino acid-N and protein-N output by this route were both negligible. Alternative nitrogen products – trimethylamine,trimethylamine oxide, uric acid, and nitrite + nitrate – were not excreted in detectable quantities. Creatine-N and creatinine-N outputs were detected but contributed only a small fraction to total nitrogen excretion(&lt;1.4%). Despite the wide scope of nitrogenous end products investigated, a considerable proportion (12–20%) of nitrogen excretion remains unknown. Possible alternative end products and methodological considerations are proposed to explain this phenomenon. The findings described above were used to recalculate the nitrogen quotient(NQ=ṀN/ṀO2)on trout that had been either fasted or fed various daily rations (1%, 3% or 5% dry food per unit wet body mass per day). Feeding increased oxygen consumption (ṀO2)and total-N excretion (ṀN). The NQ is often used as a measure of protein utilisation in aerobic metabolism and assumes that all protein (and amino acid) fuels are converted by oxidation to nitrogenous waste products that are excreted. However, the results showed that calculation of the NQ based on total nitrogen excretion may overestimate protein utilisation in aerobic metabolism because of significant excretion of N in the form of proteins and amino acids, whereas the use of summed ammonia-N and urea-N excretion probably underestimates the contribution of protein towards aerobic metabolism. These errors increase as ration increases, because the discrepancy between total-N excretion and ammonia-N + urea-N excretion increases.
Dogmas and controversies in the handling of nitrogenous wastes: Ammonia tolerance in the oriental weatherloachMisgurnus anguillicaudatus
Authors: Tsui T. K. N. , Randall D. J. , Hanson L. , Farrell A. P. , Chew S. F. , Ip Y. K. 
Published: May 2004

SUMMARYThe oriental weatherloach Misgurnus anguillicaudatus is an extremely ammonia-tolerant fish. Many ammonia-protection mechanisms have been reported in this fish. Six strategies used by this fish to deal with the problem of excess ammonia are described. The fish can (1) reduce ammonia production through reduction in protein and/or amino acid catabolism; (2)reduce ammonia production and obtain energy through partial amino acid catabolism leading to alanine formation; (3) detoxify ammonia to glutamine;(4) tolerate very high ammonia levels in its tissues; (5) get rid of ammonia as NH3 gas and, probably, (6) possesses background K+channels that are impermeable to NH4+. The effects of extracellular ammonia on the contraction performance of the heart from this fish were found to be the same as in rainbow trout, an ammonia-sensitive fish. It suggests that the hearts of most, if not all, fish species are protected against ammonia. MK-801, an NMDA receptor blocker, was found to have a protective effect against ammonia intoxication in the oriental weatherloach,which suggests that the NMDA receptor, as in mammals, is involved in ammonia toxicity.
Dogmas and controversies in the handling of nitrogenous wastes:Osmoregulation during early embryonic development in the marine little skate Raja erinacea; response to changes in external salinity
Authors: Steele S. L. , Yancey P. H. , Wright P. A. 
Published: May 2004

SUMMARY
Marine elasmobranchs retain relatively high levels of urea to counterbalance the osmotic strength of seawater. Oviparous species, such as the little skate Raja erinacea, release encapsulated embryos that hatch after about 9 months on the seafloor. To study the ureosmotic capability of skate embryos, we measured a variety of possible osmolytes and ornithine–urea cycle (OUC) enzyme activities in little skate embryos,and determined their physiological response to dilute seawater (75% SW)exposure relative to controls (100% SW). The urea:trimethylamine oxide (TMAO)+ other osmolytes ratio was 2.3–2.7:1. At the earliest stage of development investigated (4 months), there were significant levels of the key OUC enzyme, carbamoyl phosphate synthetase III, as well as ornithine transcarbamoylase, arginase and glutamine synthetase, providing evidence for a functional OUC. Embryos (4 and 8 months) survived and recovered from exposure to 5 days of 75% SW. There was a significant increase in the rate of urea excretion (five- to tenfold), no change in OUC enzyme activities, and significant decreases in the tissue content of urea, TMAO and other osmolytes in embryos exposed to 75% SW compared to 100% SW. Taken together, the data indicate that little skate embryos synthesize and retain urea, as well as a suite of other osmolytes, in order to regulate osmotic balance with the external environment. Interestingly, these ureosmotic mechanisms are in place as early as 4 months, around the time at which the egg capsule opens and the embryo is in more direct contact with the external environment.
Contributions of different NaPi cotransporter isoforms to dietary regulation of P transport in the pyloric caeca and intestine of rainbow trout
Authors: Sugiura Shozo H. , Ferraris Ronaldo P. 
Published: May 2004

SUMMARYThe anatomical proximity and embryological relationship of the pyloric caeca (PC) and small intestine of rainbow trout has led to the frequent assumption, on little evidence, that they have the same enzymes and transporters. In trout, the PC is an important absorptive organ for dietary nutrients, but its role in dietary P absorption has not been reported. We found that apical inorganic phosphate (Pi) transport in PC comprises carrier-mediated and diffusive components. Carrier-mediated uptake was energy-and temperature-dependent, competitively inhibited and Na+-independent, and greater than the Na+-dependent intestinal uptake. Pi uptake in PC was pH-sensitive in the presence of Na+. Despite the active Pi transport system in PC, high postprandial luminal Pi concentrations (∼20 mmol l–1)indicate that diffusive uptake represents ∼92% of total Pi uptake in PC of fed fish. The nucleotide sequence of a sodium-phosphate cotransporter(NaPi-II) isoform isolated from PC was ∼8% different from the intestinal NaPi cotransporter. PC-NaPi mRNA was abundant in PC but rare in the intestine,whereas intestinal NaPi mRNA was abundant in the intestine but scarce in PC. Dietary P restriction reduced serum and bone P concentrations, increased intestine-type, but not PC-type, NaPi mRNA in PC, and increased Pi uptake in intestine but not in PC. Intestine-type NaPi expression may be useful for predicting dietary P deficiency.
Activation patterns of the tongue-projector muscle during feeding in the imperial cave salamanderHydromantes imperialis
Authors: Deban Stephen M. , Dicke Ursula 
Published: May 2004

SUMMARYSalamanders of the genus Hydromantes project their tongues the greatest distance of any amphibian to capture prey, up to 80% of body length or approximately 6 cm in an adult individual. During tongue projection on distant prey, the tongue is shot ballistically and the tongue skeleton leaves the body of the salamander entirely. We investigated an aspect of the motor control of this remarkable behavior by examining electromyographic patterns within different regions of the tongue-projector muscle, the subarcualis rectus (SAR). SAR activation is strongly modulated, and features of this modulation can be predicted by tongue-projection distance (i.e. prey distance). The strap-like buccal portion of the SAR is always activated first and for the longest duration, compared to any other region. It is in a position to transmit force generated by the posterior SAR to the floor of the mouth, where it originates. The posterior SAR encompasses and applies force to the epibranchial of the tongue skeleton, and its activation pattern gradually changes from a posterior-to-anterior wave of activation onset during short-distance projection to an all-at-once pattern during the most extreme long-distance (ballistic) projection. The duration of activity and EMG area of each recorded region of the SAR increase with increasing prey distance,showing greater muscle recruitment during long-distance projection. No effect of prey-capture success was observed in the EMG patterns, indicating that SAR activation is controlled in a feed-forward manner.
Dogmas and controversies in the handling of nitrogenous wastes: Is exogenous ammonia a growth stimulant in fish?
Authors: Wood Chris M. 
Published: May 2004

SUMMARY
Traditionally, waterborne ammonia is considered a toxicant that decreases productivity in aquaculture. However, several recent studies have suggested,but not proven, that growth of salmonids might actually be stimulated by chronic exposure to very low levels of ammonia. In the present study, two 70–71 day growth experiments were conducted under rigorously controlled experimental conditions with juvenile rainbow trout at total ammonia concentrations ([TAmm])=0, 70 and 225 μmol l–1, pH 7.6. In the first series, a small-scale laboratory proof-of-principle study at 15°C, there was a significant stimulation of mass gain, gross food conversion efficiency, condition factor and protein production per fish at [TAmm]=70 μmol l–1, without an increase in voluntary food consumption or change in `in-tank' O2 consumption or ammonia excretion rates. These growth stimulatory effects were not seen at[TAmm]=225 μmol l–1, where the fish consumed more food, and excreted more ammonia, yet achieved the same mass and protein content as the controls. In the second series, a larger study conducted in an aquaculture facility at 6.5°C, growth rate, conversion efficiency and protein production per fish over 71 days were all significantly stimulated at [TAmm]=225 μmol l–1, but not at 70 μmol l–1, without any change in voluntary food consumption. These effects occurred despite an early inhibition of growth at both [TAmm] levels. When ration was restricted, growth was reduced and there were no longer any differential effects attributable to[TAmm]. While the effective levels of[TAmm] differed between the two series, in both, the PNH3 level stimulating growth was ∼23μtorr. The results are interpreted as reflecting either a stimulation of ammonia incorporation into amino acids and protein synthesis and/or a reduction in metabolic costs. The finding that low levels of exogenous ammonia can serve as a growth stimulant without altering food consumption may be important for aquacultural practice, and challenges traditional dogma that the effects of ammonia are detrimental to growth.
Sex-dependent effects of gonadal steroids and cortisol on cardiac contractility in rainbow trout
Authors: Farrar Richard S. , Rodnick Kenneth J. 
Published: May 2004

SUMMARY
The purpose of this study was to determine whether steroid hormones modulate cardiac function in rainbow trout (Oncorhynchus mykissWalbaum). We assessed the effects of exogenously administered steroids on isolated ventricle strips and report that physiological concentrations of androgens, 17β-estradiol and cortisol rapidly (&lt;10 min) enhance inotropism (30–40%) in a sex-specific manner. These effects were specific to the hormones studied, absent if animals were anesthetized chemically and dependent upon steroid concentration and contraction frequency. Based on the use of specific steroid receptor antagonists and key enzyme inhibitors, it appears that testosterone, 11-ketotestosterone and cortisol each act through specific intracellular receptors in males and that the positive inotropism requires the synthesis of polyamines and nitric oxide. Cortisol and 17β-estradiol, but not androgens, had similar effects in females and also involved similar signaling pathways. Androgen and cortisol effects were additive in males but cortisol and 17β-estradiol were not additive in females, suggesting sex differences in the pathways through which these hormones stimulate inotropism. In summary, gonadal steroids and cortisol promote ventricular contractility in a sex-dependent manner through mechanisms that appear multifaceted. Ultimately, steroid-mediated improvements in cardiac performance might involve non-genomic pathways and be physiologically important during migration, spawning or stressful periods.
How do cormorants counter buoyancy during submerged swimming?
Authors: Ribak Gal , Weihs Daniel , Arad Zeev 
Published: May 2004

SUMMARYBuoyancy is a de-stabilizing force for diving cormorants that forage at shallow depths. Having to counter this force increases the cost of transport underwater. Cormorants are known to be less buoyant than most water birds but are still highly buoyant (ρ=∼0.8 kg m–3) due to their adaptations for aerial flight. Nevertheless, cormorants are known to dive at a wide range of depths, including shallow dives where buoyancy is maximal. We analyzed the kinematics of underwater swimming of the great cormorant(Phalacrocorax carbo sinensis) in a shallow pool to discover and evaluate the mechanisms countering buoyancy while swimming horizontally. The birds maintained a very uniform cyclic paddling pattern. Throughout this cycle, synchronized tilting of the body, controlled by the tail, resulted in only slight vertical drifts of the center of mass around the average swimming path. We suggest that this tilting behavior serves two purposes: (1) the elongated bodies and the long tails of cormorants, tilted at a negative angle of attack relative to the swimming direction, generate downward directed hydrodynamic lift to resist buoyancy and (2) during the propulsive phase, the motion of the feet has a significant vertical component, generating a vertical component of thrust downward, which further helps to offset buoyancy. The added cost of the drag resulting from this tilting behavior may be reduced by the fact that the birds use a burst-and-glide pattern while swimming.
Dogmas and controversies in the handling of nitrogenous wastes: Excretion of nitrogenous wastes in human subjects
Authors: Kamel Kamel S. , Cheema-Dhadli Surinder , Shafiee Mohammad A. , Halperin Mitchell L. 
Published: May 2004

SUMMARY
Two major nitrogenous waste products, urea and ammonium(NH4+), are produced in humans when proteins are oxidized, and in this manuscript their excretions are examined from two perspectives. First, the specific physiology of each nitrogenous waste is reviewed and the current dogmas summarized. Second, their excretions are considered in the context of integrative physiology, i.e. the need to ensure that the urine composition is appropriate to minimize the risk of kidney stone formation. After the latter analysis, weak links in our understanding of the overall physiology become apparent and a conundrum is defined. The conundrum for the excretion of urea focuses on the fact that urea is not an effective osmole in the medullary-collecting duct when vasopressin acts. As a result, it appears that urinary urea cannot prevent a large decline in the urine flow rate and thereby minimize the risk of forming kidney stones in electrolyte-poor urine. The conundrum for the excretion of NH4+ is: high rates of NH4+excretion require a low urine pH, yet a pH ∼6.0 must be maintained in order to reduce the risk of precipitating uric acid in the urine. Possible ways of resolving these conundrums require novel physiological interpretations.
A Retrospective Evaluation of Vitamin K1 Therapy to Reverse the Anticoagulant Effect of Warfarin
Authors: Fan Jingyang , Armitstead John A. , Adams Aimee G. , Davis George A. 
Published: May 2004

Study Objective. To assess compliance with the 2001 consensus guidelines of the American College of Chest Physicians (ACCP) regarding administration of vitamin K1 to reverse the anticoagulant effect of warfarin.Design. Retrospective chart review.Setting. University teaching hospital.Patients. Fifty‐five adult inpatients who received both warfarin and vitamin K1 between September 2001 and January 2002.Measurements and Main Results. The patients' medical records were evaluated; data were collected on patient demographics and on vitamin K1 dosage and route of administration, warfarin dosage, and international normalized ratio (INR) before and after vitamin K1 administration. Administration routes and 87 doses of vitamin K1 prescribed for the 55 patients were assessed for compliance with the ACCP guidelines. Administration routes were subcutaneous (40.2% of doses), intravenous (35.6%), oral (13.8%), and intramuscular (10.3%). The most frequently prescribed dose of vitamin K1 was 10 mg (32.2%), followed by 2 mg (21.8%) and 5 mg (18.4%). Rates of compliance with the ACCP guidelines categorized by INR value were as follows: INR below 5, 12.2%; INR 5–9, 27.8%; INR between 9 and 20, 26.7%; and INR above 20, 0%. Four patients had documented episodes of bleeding and received seven doses of vitamin K1. Twenty‐six patients received fresh frozen plasma with vitamin K1. Overall compliance with ACCP‐recommended doses and routes of vitamin K1 was only 17.2%.Conclusion. The most frequently prescribed administration routes for vitamin K1 were subcutaneous and intravenous, indicating that the oral route is often not used as recommended. The vitamin K1 doses prescribed for reversal of warfarin anticoagulation were highly variable, and for most (83%) patients, the recommended guidelines were not followed. The clinical significance of noncompliance with the ACCP guidelines for vitamin K1 administration warrants further study.