Association of postoperative infection and oncological outcome after breast cancer surgery.

BACKGROUND: Surgical-site infection (SSI) is a well known complication after breast cancer surgery and has been reported to be associated with cancer recurrence. The aim of this study was to investigate the association between SSI and breast cancer recurrence, adjusting for several known confounders. The secondary aim was to assess a possible association between any postoperative infection and breast cancer recurrence. METHOD: This retrospective cohort study included all patients who underwent breast cancer surgery from January 2009 to December 2010 in the Uppsala region of Sweden. Data collected included patient, treatment and tumour characteristics, infection rates and outcome. Association between postoperative infection and oncological outcome was examined using Kaplan-Meier curves and Cox regression analysis. RESULTS: Some 492 patients (439 with invasive breast cancer) with a median follow-up of 8.4 years were included. Mean(s.d.) age was 62(13) years. Sixty-two (14.1 per cent) of those with invasive breast cancer had an SSI and 43 (9.8 per cent) had another postoperative infection. Some 26 patients had local recurrence; 55 had systemic recurrence. Systemic recurrence was significantly increased after SSI with simple analysis (log rank test, P = 0.035) but this was not observed on adjusted analysis. However, tumour size and lymph node status remained significant predictors for breast cancer recurrence on multiple regression. Other postoperative infections were not associated with recurrence. CONCLUSION: Neither SSI nor other postoperative infections were associated with worse oncological outcome in this study. Rather, other factors that relate to both SSI and recurrence may be responsible for the association seen in previous studies.

Effect of pH on the rheological and structural properties of gels of water-washed chicken-breast muscle at physiological ionic strength.

Adjustment of pH from 6.4 to neutrality improved gelling ability and water-holding capacity of twice water-washed, minced chicken-breast muscle significantly at physiological ionic strength, at which the majority of the myofibrillar proteins, including myosin, are not soluble. A strain value of 2.2 was obtained at neutral pH. Myofibrils were the main components of the gel network at both pH 6.4 and 7.0; however, the myofibrillar distribution varied with the pH value. At pH 6.4, myofibrils formed a network of localized aggregates leaving large voids between, whereas at neutral pH, an evenly distributed network of myofibrils was formed. In addition, at neutral pH, a network of fine strands was found within the network of myofibrils. The network was much less developed at pH 6.4. The thin and thick filaments within each myofibrillar structure were disorganized at both pH values. The intramyofibrillar spaces were larger at neutral pH than at pH 6.4. It was proposed that adjustment of pH to neutrality increased electrostatic repulsion leading to a more even distribution of the myofibrillar proteins, a key factor responsible for the improved gel strength and water-holding capacity.

Childbearing and the risk of parathyroid adenoma--a dominant cause for primary hyperparathyroidism.

OBJECTIVES: To explore possible associations between the reproductive history amongst women and the risk of parathyroid adenoma (PA). DESIGN: Two nationwide Swedish registries. The Fertility Register included data on more than 3.4 million livebirths between 1943 and 1992 amongst Swedish females born 1925-72. The Cancer Register encompasses more than 1800 women with a diagnosis of PA 1960 until 1992. SETTING: All women resident in Sweden 1960-92. SUBJECTS: Cases were all 1800 women born 1925-72 reported to the Swedish Cancer Registry with a histopathological diagnosis of PA. Five controls were selected at random for each case by matching for the month and year of birth. Conditional logistic regression was used to estimate relative risks of PA. MAIN OUTCOMES: Parathyroid adenoma. RESULTS: High parity (four or more live births) was associated with an increased risk of PA. Amongst women with a diagnosis of PA before menopause (i.e. the age of 50 years) there was an increased risk of PA with younger age at first childbirth. Nulliparous women were at increased risk for PA before menopause, and at decreased risk after menopause. CONCLUSIONS: There is an association between childbearing and the risk of PA, which has not previously been demonstrated, but the underlying biological mechanisms remain to be determined.

Effect of pH on lipid oxidation using trout hemolysate as a catalyst: a possible role for deoxyhemoglobin.

Hemoglobin-mediated lipid oxidation was studied by adding hemolysate to washed cod muscle. Three pH values were examined (pH 7.6, 7.2, and 6.0). The lag time prior to rancidity and thiobarbituric acid reactive substance development decreased greatly as the pH was reduced (p < 0.01). Formation of methemoglobin due to autoxidation of the heme pigment was found to occur more rapidly at reduced pH. Also, the level of deoxyhemoglobin was found to sharply increase with pH reduction in the range of pH 7.6-6.0. This suggested a potential role for deoxyhemoglobin as a catalyst. ATP lowered hemoglobin oxygenation at pH 7.2. Peroxidation of linoleic acid by oxy/deoxyhemoglobin and methemoglobin was investigated at two levels of preformed lipid hydroperoxides. At a reduced level of preformed lipid hydroperoxides, oxy/deoxyhemoglobin stimulated peroxidation of linoleic acid, whereas methemoglobin did not. At the higher level of preformed lipid hydroperoxides, both oxy/deoxyhemoglobin and methemoglobin were active. This investigation suggests that reduced hemoglobins played an important role in lipid oxidation processes.

Kinetics of oxidation of the lipids and proteins of cod sarcoplasmic reticulum.

Lipid and protein oxidation in an NADH-Fe enzymic and an ascorbate-Fe nonenzymic system were determined simultaneously. The nonenzymic iron-reducing system gave rapid oxidation of lipid that leveled off at values much lower than those achieved in the enzymic system, which showed a continuous increase over the 1 or 2 h incubation times used. Protein sulfhydryl oxidation was more rapid in the nonenzymic system for total and accessible sulfhydryl groups, but the enzymic system oxidized the inaccessible sulfhydryl groups more rapidly. Both lipid and protein oxidations appeared to begin simultaneously. In the enzymic system, more lipid oxidation was achieved on a molar basis than oxidation of protein sulfhydryl groups, while in the nonenzymic system this was reversed. These data probably reflect the site specificity of the production of oxidizing elements in the two systems. The greater lipid oxidation in the enzymic system suggests that this may be the more important ferric iron-reducing system during storage of fish muscle.

The early experiences of a national system for the identification and assessment of emerging health care technologies in Sweden.

This article presents the experiences from a pilot study and the establishment of a permanent system called SBU Alert. The question of establishing a system for the identification and assessment of emerging technologies in health care in Sweden has been on the agenda since the late 1980s. The demand came primarily from policy makers. The pilot study showed that the awareness of the project in the target group (politicians, leading managers, hospital directors, and senior medical advisors) was high. Almost all of those who replied to an assessment questionnaire were in favor of a continuation of the work. In 1997, the Swedish Council on Technology Assessment in Health Care (SBU) was selected to establish a permanent organization. This work has resulted in the identification of a number of methodological problems and tentative solutions concerning all components in the SBU Alert system. We have found that a system for systematic identification and early assessment of emerging technologies is a new and promising tool in the health technology assessment arsenal. Still, experiences are limited. Methodology and the impact of early judgments on decision making need further evaluation.

Influence of histidine on lipid peroxidation in sarcoplasmic reticulum.

The free amino acid, histidine, which exists at high concentrations in some muscle systems, has previously been demonstrated to both inhibit and activate lipid peroxidation in membrane model systems. This study sought to characterize the specificity of histidine's effect on iron-catalyzed enzymatic and nonenzymatic lipid peroxidation. Under conditions of activation (histidine added to the reaction mixture after ADP and ferric ion), alpha-amino, carboxylate, and pyrrole nitrogen were demonstrated to be involved by kinetic techniques in the activation of the enzymatic system. It is hypothesized that a mixed ligand complex (iron, ADP, and histidine) formed may allow rapid redox cycling of iron. While increasing concentrations of histidine led to increasing levels of stimulation in the enzymatic system, the maximum stimulation of a nonenzymatic lipid peroxidation system of ascorbate and ferric ion occurred at histidine concentrations near 2.5 mM. Inhibition of a nonenzymatic system (ferrous ion), on the other hand, occurred at all concentrations of histidine when the ferrous ion was exposed to ADP prior to histidine. In enzymatic systems, under conditions when the ferric ion was exposed to histidine prior to ADP, inhibition of lipid peroxidation by histidine also occurred. The inhibitory effect of histidine was ascribed to the imidazole group and may arise from the formation of a different iron complex or the acceleration of polymerization, dehydration, and insolubilization of the ferric ion by the imidazole nitrogen. The demonstrated ability of histidine to affect in vitro lipid peroxidation systems raises the possibility that this free amino acid may modulate lipid peroxidation in vivo.

Effect of NaCl on catalysis of lipid oxidation by the soluble fraction of fish muscle.

Sodium chloride stimulated catalysis of oxidation of phosphatidylcholine liposomes by the soluble fraction of mackerel muscle. Chloride was determined to be the active component of the salt in this system. Sulfate also stimulated lipid oxidation. No difference was observed with either anion among sodium, potassium, or lithium cations. Redox iron was involved in the chloride stimulation of lipid oxidation by the press juice. Part of the chloride stimulation of the press juice was mediated through the high molecular weight (greater than 5 kdalton) fraction. Chloride improved the pro-oxidative effect of ascorbate on rat liver ferritin in vitro. It did not appear that production of chlorine radical by peroxidase was involved in the stimulatory effect of chloride.

A comparison of dogfish and porcine pancreatic lipases.

1. A 16-fold purification of lipase activity from the pancreas of the dogfish (Squalus acanthias) was obtained by preparative isoelectric focussing. 2. The dogfish enzyme has a higher pH optimum (8.5) and a broader spectrum of activity above and below its optimum than a commercial porcine lipase preparation (optimum, 7.5). 3. The temperature optimum of dogfish lipase was 35 degrees C and it displayed greater stability than the porcine lipase preparation towards higher temperatures in the absence of substrate. 4. Dogfish lipase was active against a broad range of triacylglycerols and a wax ester. It had greater relative activity against the latter than the porcine lipase but hydrolyzed low mol. wt fatty acids less readily. In general, the effect of temperature was less on the dogfish enzyme than the porcine one.

A comparison of dogfish and bovine chymotrypsins.

Bovine and dogfish chymotrypsins were compared to determine if chymotrypsin from a poikilothermic organism (spiny dogfish (Squalus acanthias] adapted to low temperatures possessed catalytic properties different from those of the same enzyme from a warm-blooded animal. An improved procedure was developed for isolating dogfish pancreatic chymotrypsin. The least hydrophobic and smallest substrate used, p-nitrophenyl acetate, had similar enthalpies of association (delta Ha) with both enzymes, whereas larger, more hydrophobic substrates had delta Ha values that were of opposite sign for the two enzymes. As the temperature increased, the association constants (1/Ks) for p-nitrophenyl valerate and p-nitrophenyltrimethyl acetate increased for dogfish chymotrypsin and decreased for bovine chymotrypsin, while the free energies of association (delta Ga) remained relatively constant. Acylation of chymotrypsin was 1.5-2.5 times slower in the dogfish enzyme than in the bovine enzyme except below 15 degrees C with p-nitrophenyltrimethyl acetate. delta H++ for acylation by p-nitrophenyltrimethyl acetate were 2.0 kcal/mol for the dogfish enzyme and 10.2 kcal/mol for the bovine, whereas delta H++ values were only slightly lower in the dogfish enzyme for the other two substrates. For all substrates, the deacylation rate constant (kcat) was greater with dogfish chymotrypsin than bovine. However, the free energies of activation (delta G++) for deacylation were nearly equal between the two enzymes for each of the substrates.

Some kinetic properties of dogfish chymotrypsin.

A comparison of some kinetic properties was made between bovine chymotrypsin and chymotrypsin isolated from the spiny dogfish (Squalus acanthias). The major difference between the two enzymes was observed in the molecular activity (kcat), with the dogfish enzyme being two to three times more active than the bovine enzyme. The exact difference was dependent on the substrate and assay conditions. The two enzymes showed similar kinetic properties with respect to the following: similar inhibition by indole and naphthol derivatives, activities vs BTEE and a series of n-fatty acid esters of p-nitrophenol, KM values, optimal pH and temperature and activation energies.

In vitro lipid oxidation modifies proteins and functional properties of sarcoplasmic reticulum.

Changes in protein and fatty acid compositions of flounder sarcoplasmic reticulum during NADH plus ascorbate-dependent lipid peroxidation in vitro were related to the ability of the sarcoplasmic reticulum to sequester Ca+2. Progressive accumulation of high-molecular-weight protein components occurred concomitantly with loss of Ca+2-sequestering activity. Part of this polymerized protein may be the dimer or trimer of Ca+2, Mg+2-ATPase. Loss in Ca+2, Mg+2-ATPase protein could account for over 60% of the polymerized protein. Rate of loss of polyunsaturated fatty acids was C22:6 greater than C20:4 greater than C20:5 greater than C22:5. Loss of polyunsaturated fatty acids and accumulation of thiobarbituric acid-reactive substances occurred concomitantly with protein polymerization.

Effect of age of winter flounder on some properties of the sarcoplasmic reticulum.

Sarcoplasmic reticulum (SR) from winter flounder (Pseudopleuronectes americanus) of various ages was investigated with regard to fluorescent age pigment (FAP), potential of enzymic lipid peroxidation, fatty acid composition, protein pattern and Ca2+-sequestering ability. FAP accumulation, protein pattern and Ca2+-sequestering ability were also evaluated after the SR were incubated in vitro with the peroxidizing cofactors: NADH, ADP and Fe3+. No difference in FAP content was observed in SR isolated from fish of different ages. However, a higher accumulation of FAP in muscle tissue from old fish was observed. A slow but significant increase in FAP in SR was observed when the SR from both young and old fish were incubated with peroxidizing cofactors. It was demonstrated that 4-year-old fish had higher levels of NADH-dependent lipid peroxidation in their SR than 2-year-old fish. No differences in fatty acid composition were observed in the SR of fish aged from 2 to 8 years old. Two species of high-molecular-weight protein were found to increase in SR isolated from aging fish. These species resembled the polymerized proteins derived after incubation of the SR with the peroxidizing cofactors. Ca2+-uptake decreased when the SR was incubated with peroxidizing cofactors, but the results are difficult to interpret since Ca2+-uptake of SR was affected by captive stress.

Characterization of trimethylamine-N-oxide (TMAO) demethylase activity from fish muscle microsomes.

A crude microsomal fraction isolated from red hake (Urophycis chuss) muscle demethylated trimethylamine-N-oxide (TMAO). Two cofactor systems were capable of stimulating activity; the system of NADH and FMN required anaerobic conditions while the other system, composed of iron and cysteine and/or ascorbate functioned in the presence or absence of oxygen. The components of each cofactor system functioned synergistically and kinetic parameters were established for each. Of several amine compounds common to fish muscle, TMAO was the only substrate demethylated by the microsomes. Activity was inhibited by iodoacetamide, potassium cyanide, and sodium azide under certain conditions, but not by carbon monoxide. An enzymic nature of the reaction was demonstrated by the properties of heat lability, sensitivity to protease treatment, the requirement of microsomes for TMAO demethylation and by the exhibition of typical hyperbolic kinetics with respect to substrate (TMAO). Moreover, TMAO demethylation by the microsomes was 3 to 4 orders of magnitude faster than the non-enzymic reaction and the reaction was specific for dimethylamine (DMA) as product. It appears the two cofactor systems may share a common catalytic unit in the process of TMAO demethylation.

Partial purification of trimethylamine-N-oxide (TMAO) demethylase from crude fish muscle microsomes by detergents.

Detergent treatments were examined for their efficacy in purifying trimethylamine-N-oxide (TMAO) demethylase activity from fish muscle microsomes. Tritons X-100 and X-45, deoxycholate, Brijs, Tweens 20, 65, and 80, and SDS were generally ineffective in solubilizing demethylase activity from this membrane fraction, at concentrations up to 10 mg detergent per mg protein. In all of these cases, specific activity became enriched in the particulate fraction obtained post-treatment. Highest fold-purification was achieved by using 10 mg SDS per mg protein in 5 mM histidine, pH 7.0 at 10-14 degrees C. Activity was relatively stable to the presence of SDS at this level, and with this treatment, TMAO demethylase activity became purified in the resultant particulate fraction 28- and 58-fold for activity stimulated by ascorbate-iron-cysteine and FMN-NADH, respectively. The presence of urea or 2-mercaptoethanol, or sonication of the SDS-microsome suspension during purification resulted in significant losses of recovered activity. This partially purified fraction represented about 1% of the original microsomal protein and SDS-PAGE revealed the presence of several protein components. The partially purified demethylase could utilize the same two cofactor systems as the native microsomes. It displayed a curvilinear dependence on iron for activity and a sigmoidal response for cysteine. Utilization of NADH, FMN, and ascorbate differed for the purified fraction as compared to the microsomes. Substrate inhibition by TMAO was observed for the partially purified preparation, whereas saturation kinetics were previously noted for microsomal activity.(ABSTRACT TRUNCATED AT 250 WORDS)