Heterogeneity of colon cancer patients reported as emergencies.

BACKGROUND: Up to one-fourth of all colon cancer patients are reported as emergencies, and the aim of the present study was to scrutinize mode of presentation in this group. MATERIALS AND METHODS: All reported cases of emergency (n = 263) and randomly selected elective controls (1:2) of colon cancer in four Swedish counties 2006-2008 were eligible (n = 854). Symptoms and aspects of management were retrieved from surgery and primary care records. Outcomes were compared using Kaplan-Meier estimates and Cox regression. RESULTS: Among patients reported as emergencies, 158/263 (60 %) underwent operation within three days (acute), and 105 (40 %) after more than 3 days (subacute). In the latter group, 20/94 (21 %) had reported two symptoms, and 31/94 (33 %) had reported three or more symptoms associated with colon cancer to primary care during the last 12 months prior to surgery. In total, 46/105 (44 %) had already had an examination of the large bowel, and 52/105 (50 %) were stage IV, as opposed to 36/158 (23 %) in the acute group and 83/577 (15 %) in the elective group (p < 0.001). Mortality at 30 and 90 days was 15.2 and 35.6 % in the subacute group, 8.2 and 14.9 % in the acute group (p = 0.001), and 1.9 and 4.3 % in the elective group (p < 0.001); 5-year survival was 28.3, 40.1, and 57.8 %, respectively, in the three groups (p < 0.001). The hazard ratio, adjusted for age, sex, and stage, was 1.88 95 % confidence interval (CI) 1.5-2.4) for the acute group and 2.29 (95 % CI 1.7-3.1) for the subacute group. CONCLUSIONS: Colon cancer patients reported as emergencies but operated upon more than three days after admission had the worst outcome. Efforts to decrease the interval between admission and surgery is one important aspect of care, but wider attention must also be paid to this group of patients.

Emergency presentation and socioeconomic status in colon cancer.

BACKGROUND: Emergency presentation affects up to every fourth patient with colon cancer, and is associated with worse outcomes. The aim of this study was to investigate any association between socioeconomic status (SES) and mode of presentation in colon cancer. MATERIALS AND METHODS: Individually attained data on civil status, education and income were linked to quality registries for colon cancer in two large Swedish regions 1997-2006 (n = 12 293) and analyzed by logistic regression, adjusting for age, sex, stage, region and socioeconomic variables. RESULTS: The frequency of emergency presentation was 23%; 27.8% among patients above the age of 80, and 20.0% among patients aged 70-79 (p < 0.001). There was no difference between men and women (22.6% vs. 23.8%; p = 0.1). Among patients with stage IV colon cancer, 34.6% presented as emergencies. Odds ratio for an emergency presentation in unmarried patients was 1.24 (96% CI 1.04-1.48), and for unmarried patients above the age of 80, OR was 1.45 (95% CI 0.98-2.13). Among patients below the age of 70 with compulsory education only, OR was 1.22 (95% CI 0.98-1.48). For patients within the lowest income quartile (Q1), OR was 1.24 (95% CI 1.04-1.49). This was most pronounced in men (OR 1.34; 95% CI 1.40-1.72), in patients below the age of 70 (OR 1.36; 95% CI 1.02-1.82), and above the age of 80 (OR 1.41; 95% CI 1.00-1.98). CONCLUSION: Emergency presentation of colon cancer is consistently associated with socioeconomic factors, and this must be considered in efforts aimed at reducing the overall frequency of emergency cases.

Erythrocyte antioxidant protection of rose hips (Rosa spp.).

Rose hips are popular in health promoting products as the fruits contain high content of bioactive compounds. The aim of this study was to investigate whether health benefits are attributable to ascorbic acid, phenols, or other rose-hip-derived compounds. Freeze-dried powder of rose hips was preextracted with metaphosphoric acid and the sample was then sequentially eluted on a C(18) column. The degree of amelioration of oxidative damage was determined in an erythrocyte in vitro bioassay by comparing the effects of a reducing agent on erythrocytes alone or on erythrocytes pretreated with berry extracts. The maximum protection against oxidative stress, 59.4 ± 4.0% (mean ± standard deviation), was achieved when incubating the cells with the first eluted meta-phosphoric extract. Removal of ascorbic acid from this extract increased the protection against oxidative stress to 67.9 ± 1.9%. The protection from the 20% and 100% methanol extracts was 20.8 ± 8.2% and 5.0 ± 3.2%, respectively. Antioxidant uptake was confirmed by measurement of catechin by HPLC-ESI-MS in the 20% methanol extract. The fact that all sequentially eluted extracts studied contributed to protective effects on the erythrocytes indicates that rose hips contain a promising level of clinically relevant antioxidant protection.

Emergency presentation of colon cancer is most frequent during summer.

AIM: The frequency of emergency colon cancer (ECC) was determined using a reproducible definition of 'emergency' to analyse the impact of mode of presentation on long-term prognosis and to search for risk factors for an emergency presentation. METHOD: All patients with colon cancer treated at one Swedish GDH between 1996 and 2005 (N = 604) were eligible. Patients admitted through the emergency room, operated on within three days and with an emergency condition confirmed at surgery were classified as ECC. Survival was analysed by Kaplan-Meier estimates and risk of death by Cox regression. RESULTS: The rate of ECC was 97/585 (17%). Patients with ECC were older (median 77 vs 74, P = 0.02), they had more stage III and IV cancers (65%vs 47%; χ(2) = 9.4, P < 0.001) and had a cancer located in the caecum less often (20%vs 33%, χ(2) = 4.3 P = 0.04). ECC were most frequent between June and August (36%), whereas elective cases were evenly distributed throughout the year (χ(2) = 7.8; P = 0.049), Crude 5-year survival was 18% in ECC and 38% in the elective group (P < 0.001). The hazard ratio for death within five years in ECC, with 30-day mortality excluded and adjusted for age and sex was 2.25 (95% CI; 1.42-3.55). CONCLUSION: Emergency presentation of colon cancer is an independent and adverse risk factor for long-term survival. The causes of a seasonal variation need to be clarified.

Association models for a multivariate binary response.

Models for a multivariate binary response are parameterized by univariate marginal probabilities and dependence ratios of all orders. The w-order dependence ratio is the joint success probability of w binary responses divided by the joint success probability assuming independence. This parameterization supports likelihood-based inference for both regression parameters, relating marginal probabilities to explanatory variables, and association model parameters, relating dependence ratios to simple and meaningful mechanisms. Five types of association models are proposed, where responses are (1) independent given a necessary factor for the possibility of a success, (2) independent given a latent binary factor, (3) independent given a latent beta distributed variable, (4) follow a Markov chain, and (5) follow one of two first-order Markov chains depending on the realization of a binary latent factor. These models are illustrated by reanalyzing three data sets, foremost a set of binary time series on auranofin therapy against arthritis. Likelihood-based approaches are contrasted with approaches based on generalized estimating equations. Association models specified by dependence ratios are contrasted with other models for a multivariate binary response that are specified by odds ratios or correlation coefficients.

Cytokine response after acute hyperbaric exposure in the rat.

Intravascular gas has earlier been shown to activate leukocytes and platelets, enhance cell adhesion, and promote secretion of vasoactive substances from platelets. Since decompression is known to release gas bubbles in the bloodstream, the present study was undertaken to investigate the effect of a standardized decompression trauma on inflammatory mediators. Two series of experiments were performed in which male Wistar rats were subjected to a sublethal decompression trauma using a dry pressure chamber. Postdive measurements of cytokine levels were performed to look for signs of an inflammatory reaction. All animals subjected to a decompression trauma showed postdive signs of mild to severe decompression illness (DCI) and measurements of interleukin-6 (IL-6) indicated a postdive increase in the majority of these animals. Our finding of a postdive increase in IL-6 suggests that an inflammatory response, probably created by a blood-gas interface, may be a factor in the process leading to DCI.

Measurement by ICP-MS of lead in plasma and whole blood of lead workers and controls.

OBJECTIVES: To test a simple procedure for preparing samples for measurement of lead in blood plasma (P-Pb) and whole blood (B-Pb) by inductively coupled plasma mass spectrometry (ICP-MS), to measure P-Pb and B-Pb in lead workers and controls, and to evaluate any differences in the relation between B-Pb and P-Pb between people. METHODS: P-Pb and B-Pb were measured by ICP-MS in 43 male lead smelter workers and seven controls without occupational exposure to lead. For analysis, plasma and whole blood were diluted 1 in 4 and 1 in 9, respectively, with a diluted ammonia solution containing Triton-X 100 and EDTA. The samples were handled under routine laboratory conditions, without clean room facilities. RESULTS: P-Pb was measured with good precision (CV = 5%) even at concentrations present in the controls. Freeze storage of the samples had no effect on the results. The detection limit was 0.015 microgram/l. The P-Pb was 0.15 (range 0.1-0.3) microgram/l in controls and 1.2 (0.3-3.6) micrograms/l in lead workers, although the corresponding B-Pbs were 40 (24-59) micrograms/l and 281 (60-530) micrograms/l (1 microgram Pb/I = 4.8 nmol/l). B-Pb was closely associated with P-Pb (r = 0.90). The association was evidently non-linear; the ratio B-Pb/P-Pb decreased with increasing P-Pb. CONCLUSIONS: By means of ICP-MS and a simple dilution procedure, P-Pb may be measured accurately and with good precision down to concentrations present in controls. Contamination of blood at sampling and analysis is no major problem. With increasing P-Pb, the percentage of lead in plasma increases. In studies of lead toxicity, P-Pb should be considered as a complement to current indicators of lead exposure and risk.

Depression after surgery for acoustic neuroma.

The purpose of this study was to establish the frequency and pattern of depressive disorders after surgery for acoustic neuroma, and to look for associations. Twenty seven patients with acoustic neuroma underwent thorough psychiatric assessment before surgery and at three and 12 months after surgery. Three patients had a depressive disorder in the preoperative assessment. Of the remaining 24 patients, nine (38%) had a depressive disorder at the three month check up. Deterioration of hearing was the only postoperative detriment associated with a depressive disorder (P = 0·024). All nine patients with a depressive disorder were women (P = 0·001), giving them a 69% incidence. None of the patients without preoperative depression required inpatient treatment for depressive disorder, but three patients out of nine still had a depressive disorder 12 months after surgery.

Influence of hyperglycemia and of hypercapnia on cellular calcium transients during reversible brain ischemia.

The object of the study was to find out how preischemic hyperglycemia (in normocapnic animals) or excessive hypercapnia (in normoglycemic animals) affect the calcium transient during ischemia, as this can be assessed by measurements of the extracellular calcium concentration ([Ca2+]e). To that extent, normocapnic-normoglycemic control animals were compared with animals with induced hyperglycemia or hypercapnia, all being subjected to 10 min of forebrain ischemia, the [Ca2+]e and d.c. potential being measured with ion-sensitive glass microelectrodes. Hyperglycemia and hypercapnia delayed the loss of ion homeostasis following induction of ischemia. Furthermore, both hyperglycemia and hypercapnia reduced the delay of Ca2+ extrusion upon recirculation. As a result, both hyperglycemia and hypercapnia significantly reduced the ischemic calcium transient, as this was assessed by calculating the duration of maximal calcium load of cells. The results make it less likely that aggravation of brain damage by hyperglycemia or excessive hypercapnia is related to a further derangement of cell calcium homeostasis.

Coupling of energy failure and dissipative K+ flux during ischemia: role of preischemic plasma glucose concentration.

The present experiments were undertaken to assess the influence of preischemic hypo- or hyperglycemia on the coupling among changes in extracellular K+ concentration (K+e) and in cellular energy state, as the latter is reflected in the tissue concentrations of phosphocreatine (PCr), Cr, ATP, ADP, and AMP, and in the calculated free ADP (ADPf) concentrations. The questions posed were whether the final release of K+ was delayed because the extra glucose accumulated by hyperglycemic animals produced enough ATP to continue supporting Na(+)-K(+)-driven ATPase activity, and whether the additional acidosis altered the ionic transients. As expected, preischemic hypoglycemia shortened and hyperglycemia prolonged the phase before K+e rapidly increased. This was reflected in corresponding changes in tissue ATP content. Thus, hypoglycemia shortened and hyperglycemia prolonged the time before the fall in ATP concentration accelerated. When tissue was frozen at the moment of depolarization, the tissue contents of ATP were similar in hypo-, normo-, and hyperglycemic groups, approximately 30% of control. This suggests that hyperglycemia retards loss of ion homeostasis by leading to production of additional ATP. However, hyperglycemia did not reduce the rate at which the PCr concentration fell, and the ATP/ADPf ratio decreased. There were marked differences in the amount of lactate accumulated between the groups. Thus, massive depolarization in hypoglycemic groups occurred at a tissue lactate content of approximately 4 mM kg-1. This corresponds to a decrease in intracellular pH (pHi) from approximately 7.0 to approximately 6.9. In the hyperglycemic groups, depolarization occurred at a lactate content of about 12 mm kg-1, corresponding to a pHi of approximately 6.4.(ABSTRACT TRUNCATED AT 250 WORDS)

Coupling of cellular energy state and ion homeostasis during recovery following brain ischemia.

The present experiments were undertaken to explore the relationship between recovery of cerebral energy state following transient ischemia, and resumption of Na+/K+ transport, as this is reflected in changes in extracellular K+ concentration ([K+]c). Cerebral energy state was evaluated by measurements of cerebral cortical concentrations of phosphocreatine (PCr), ATP, ADP, and AMP at the end of 15 min of severe, incomplete ischemia, as well as after 2 and 5 min of recirculation. Derivation of intracellular pH (pHi) allowed calculation of 'free' ADP (ADPf) and AMP (AMPf) concentrations. Changes in [K+]e were measured by an ion-sensitive microelectrode. The results showed that tissue ATP concentration, which was close to zero after 15 min of ischemia, rose to 30% of control after 2 min, and to 60% of control after 5 min of recirculation. However, since the adenine nucleotide pool was reduced by the ischemia the latter value represents extensive or complete phosphorylation of that pool, as reflected in a normalized ATP/ADPf ratio. During recirculation, the concentration of pyruvate rose, but the lactate content remained unchanged, suggesting that the substrate for oxidative metabolism was exogenous glucose. Resumption of Na+/K+ transport, as reflected in the [K+]e began after 2-3 min, and a normal [K+]e was attained within 5 min. The results demonstrate that transport of Na+ and K+ is resumed at tissue ATP concentrations which are only 30-40% of control. It is discussed whether this reflects relatively extensive rephosphorylation of the remaining adenine nucleotide pool, or if compartmentation of adenine nucleotides exists during recirculation.

A technique for brain temperature control during ischemia, suitable for measurements with ion-sensitive microelectrodes.

A technique is described for maintaining rat brain temperature constant during ischemia, a technique that also allows measurements with, and calibration of, ion-sensitive microelectrodes under defined temperature conditions. The brain temperature is controlled by a stream of air of defined temperature and humidity, which is perfused through a box enclosing the animal's head. A device for calibration of ion-sensitive microelectrodes is temperature controlled by similar principles. The air stream is delivered by a heater/humidifier that is standard in many commercial respirators/ventilators. When the relative humidity of the air stream is greater than 98%, the neocortical temperature can be maintained within less than 0.5 degrees C during 15 min of ischemia. The biological applicability of the technique is discussed.

Changes of labile metabolites during anoxia in moderately hypo- and hyperthermic rats: correlation to membrane fluxes of K+.

The objective of this study was to assess the influence of temperature on the coupling among energy failure, depolarization, and ionic fluxes during anoxia. To that end, we induced anoxia by cardiac arrest in anesthetized rats maintained at a body temperature of either 34 degrees C or 40 degrees C, measured extracellular K+ concentration (K+e), and froze the neocortex through the exposed dura for measurements of phosphocreatine (PCr), creatine (Cr), ATP, ADP, and AMP, glucose, glycogen, pyruvate and lactate content after ischemic intervals of maximally 130 s. Free ADP (ADPf) concentrations were derived from the creatine kinase equilibrium. Hypothermia reduced the initial rate of rise in K+e, and delayed the terminal depolarization; however, both hypo- and hyperthermic animals showed massive loss of ion homeostasis at a K+e of 10-15 mM. The initial rate of rise in K+e did not correlate to changes in ATP, or ATP/ADPf ratio, suggesting that temperature changes per se may control the degree of activation of K+ conductances. The results clearly showed that, in both hyper- and hypothermic subjects, energy failure preceded the sudden activation of membrane conductances for ions. The results indicate that temperature primarily influences membrane permeability to ions like K+e (and Na+), and that cerebral energy state is secondarily affected. It is proposed that the higher rate of rise of K+e at high temperatures accelerates ATP hydrolysis primarily by enhancing metabolic rate in glial cells.

Tissue PCO2 in brain ischemia related to lactate content in normo- and hypercapnic rats.

The amount of lactate formed during ischemia determines the rise in tissue PCO2 (PtCO2). Conflicting results exist on the relationship between lactate and PtCO2. The objective of this study was to settle this issue. We varied the preischemic plasma glucose concentration of normo- and hypercapnic rats, assessed tissue lactate and total CO2 contents, and determined the PCO2/lactate relationship over the lactate range 2-40 mmol kg-1. The results showed that whatever the equilibration time, the PCO2/lactate relationship was linear. The results obtained could be reproduced by a theoretical buffer system that mimics the buffering behavior of intracellular fluid. Our results bear on the question of whether compartmentation of H+ occurs during ischemia, with glial cells becoming more acid than neurons. A discontinuous PCO2/lactate relationship, with a constant PCO2 above a certain lactate content, would support this contention. Since our results demonstrate a linear relationship between lactate and PCO2 over the lactate range 2-40 mmol kg-1, they considerably weaken any argument for gross compartmentation of H+.

Coupling among changes in energy metabolism, acid-base homeostasis, and ion fluxes in ischemia.

This article attempts correlating changes in cellular energy metabolism, acid-base alterations, and ion homeostasis in ischemia and other conditions. It is emphasized that loss of ion homeostasis, with thermodynamically downhill fluxes of K+, Ca2+, Na+, Cl-, and H+, occurs because energy production fails and (or) ion conductances are increased. In ischemia, energy failure is the leading event but, in hypoglycemia, activation of ion conductances is what precipitates energy failure. The initial event is a rise in K+ e, at least in part caused by activation of K+ conductances modulated by Ca2+ or ATP/ADP ratio. Secondarily, this leads to release of excitatory amino acids and massive activation of unspecific cation (and anion) conductances. Production of H+ occurs in states characterized by energy failure (ischemia and hypoxia) or by alkalosis (hypocapnia and ammonia accumulation). H+ equilibrates between intra- and extra-cellular fluid via nonionic diffusion of lactic acid, and transmembrane fluxes of H+ or HCO3- via ion channels. Since the relationship between lactate and either pHi or pHe is linear, there are no abrupt pH shifts explaining why hyperglycemia worsens ischemic damage. The reversible insults seem to induce a sustained stimulation of H+ extrusion from cells giving rise to intracellular alkalosis and extracellular acidosis.

Perturbation of cellular energy state in complete ischemia: relationship to dissipative ion fluxes.

Loss of cellular ion homeostasis during anoxia, with rapid downhill fluxes of K+, Ca2+, Na+ and Cl-, is preceded by a slow rise in extracellular K+ concentration (Ke+), probably reflecting early activation of a K+ conductance. It has been proposed that this conductance is activated by either a rise in intracellular calcium concentration (Cai2+), or by a fall in ATP concentration. In a previous study from this laboratory (Folbergrová et al. 1990) we explored whether the early activation of a K+ conductance could be triggered by a rise in Cai2+. To that end, labile metabolites and phosphorylase a, a calcium sensitive enzyme, were measured after 15, 30, 60 and 120 s of complete ischemia ("anoxia"). In the present study, we investigated whether brief anoxia is accompanied by changes in ATP/ADP ratio, or in the phosphate potential, which could cause activation of a K+ conductance. To provide information on this issue, we added a group with 45 s of anoxia to the previously reported groups, and derived changes in intracellular pH (pHi). This allowed calculations of the free concentrations of ADP (ADPf) and AMP (AMPf) from the creatine kinase and adenylate kinase equilibria, and hence the derivation of ATP/ADPf ratios. In performing these calculations we initially assumed that the free intracellular Mg2+ concentration remained unchanged at 1 mM. However we also explored how a change in Mgi2+ of the type described by Brooks and Bachelard (1989) influenced the calculation. The results showed that ADPf must have risen to 150-200% of control within 15 s, and to 330-350% of control within 45 s of anoxia.(ABSTRACT TRUNCATED AT 250 WORDS)