Association of elevated C-reactive protein levels with an impaired prognosis in patients with surgically treated endometrial cancer

OBJECTIVE: To evaluate whether C-reactive protein (CRP) serum levels are associated with prognosis in surgically treated endometrial cancer. METHODS: In the present multicenter study, CRP serum levels were measured preoperatively in 403 surgically staged patients with endometrioid endometrial cancer. Results were correlated to clinical data. RESULTS: The mean (standard deviation) serum CRP level in patients with endometrial cancer was 1.0 (1.8) mg/dL. Serum CRP levels were associated with tumor stage (P=.01), but not with tumor grade (P=.8), lymph node involvement (P=.8), and age at diagnosis (P=.9). In a univariable survival analysis, serum CRP levels, tumor stage, tumor grade, and age at diagnosis were associated with disease-free and overall survival (all P <.001). In a multivariable Cox regression model, serum CRP levels (P=.001, P=.004), tumor stage (P <.001, P <.001), tumor grade (P=.02, P=.009), and age at diagnosis (P=.002, P=.001) were independent prognostic factors for disease-free and overall survival. CONCLUSION: Our results suggest that elevated serum CRP levels are associated with a less favorable prognosis in patients with surgically treated endometrial cancer. LEVEL OF EVIDENCE: II.     

Childhood obesity: the infancy connection

The prevalence of overweight has risen to 19% in children aged 6 to 11 years and 17% in adolescents aged 12 to 19 years. This paper examines gestational and infancy factors that influence the risk of overweight in childhood. Important factors to eliminate the infancy connection to childhood obesity include the following: (a) maternal lifestyle patterns, (b) infant feeding transitions, and (c) environmental factors. Prevention efforts need to focus on practice, research, and public policy.     

THE EFFECT OF INJECTIONS OF HEMOLYTIC STREPTOCOCCI ON SUSCEPTIBLE AND INSUSCEPTIBLE ANIMALS

1. Streptococci injected into the circulation of cats are quickly withdrawn and are found most numerously in the lung, less numerously in the liver and spleen, and in small numbers in the bone marrow, lymph nodes, muscle, and kidney. 2. The streptococci taken up by the lung are killed within 5 to 8 hours, although they remain visible in films for a number of days. In the liver they are killed less rapidly, and in the spleen a few may remain viable for a considerable period. 3. This bactericidal action may be demonstrated in pieces of excised lung but not in lung extracts, and is apparently dependent on the action of the living cell. 4. Streptococci injected into a susceptible animal, the rabbit, are also promptly removed from the circulation, but are distributed in different proportions, the liver and spleen absorbing almost as many as the lung, and the muscles also taking up an appreciable number. 5. As in the cat, the organisms taken up by the lung and liver of the living rabbit are promptly killed. Those which lodge in the muscles, however, multiply rapidly. 6. About the time that the streptococci have begun to develop in the muscles (4 to 8 hours after injection) the number in the blood stream begins to increase. 7. The increase in the blood stream is not due to exhaustion of the mechanism of their removal nor have these organisms acquired a resistance sufficient to maintain them in the blood stream of a normal animal. The septicemia, then, is probably the resuit of washing out of organisms from the infected tissues. 8. Attempts to immunize rabbits have been unsuccessful, but in certain treated animals the distribution of the organisms among the various organs approached that found in insusceptible animals; i.e., cats.     

STUDIES ON BACTERIAL ANAPHYLAXIS AND INFECTION

We have attempted in the preceding experiments the beginning of an analysis of bacterial anaphylaxis and its relation to the occurrences in the animal body during an infectious disease. We have shown that the sensitization of the tissues of guinea pigs, as indicated by the isolated uterus, required 3 to 5 days even when passive sensitization was employed, and that in these relations conditions with bacterial sensitization were entirely analogous to those revealed for serum anaphylaxis by Dale and Weil especially. It has become apparent that the sensitized uterus reacted not at all with whole bacteria or whole red cells, or, in other words, that before reaction with sensitized organs could occur an extraction or solution of the bacterial cell must take place. That bacteria yield some of their substance to the circulating blood during the course of infection was to be expected, but it has been definitely indicated, we think, by our complement fixations. The mechanism of injury in the sensitized animal or in the human being so far along in typhoid fever that antibodies have begun to develop is in part one in which antigen, derived from the bacilli and brought into solution, or rather suspension, in the blood stream, reacts with antibodies which are from the beginning, or have subsequently become, integral parts of the cell protoplasm, the entire process taking place within the cell. This last point is indicated by the failure to sensitize by simply soaking the normal uterus in antiserum. This, however, cannot be the entire story of injury. We know that typhoid antigen injected into normal animals in moderate amounts will render them gradually sick and eventually kill them. Also, a sufficient amount injected into a normal animal will occasionally produce acute symptoms, in every respect similar to the reaction produced in sensitized animals by smaller doses. We have shown that such acute symptoms in normal animals were not due in any degree to tissue sensitiveness, since even very large quantities of antigen will produce no response on the part of the normal uterus. It is reasonable to suppose, therefore, that the injury, gradual or acute, in the normal animal, is in no respect referable to tissue sensitiveness to the whole antigen, but rather must be referred to some series of phenomena which occur in the circulation. The acute shock of normal animals may possibly, therefore, be entirely due to an intravascular reaction. Whether this is one of antigen-splitting, or of antienzyme removal in the sense of Jobling is a point on which these experiments throw no light. It is true that we have never succeeded in producing acute toxic symptoms either in the whole animal or in the isolated uterus with serum from animals acutely ill. This we eliminate as negative evidence inasmuch as we believe that the toxic substances need at no given time be present in the blood stream in sufficient concentration to render such an experiment successful. They are probably absorbed and do their injury almost as rapidly as formed, an assumption which is based on the speed with which symptoms develop. It is possible, and not to be denied on the basis of any experiment that we can devise at present, that the gradual illness of the normal animal and the occasional acute shock of these animals may be based on entirely different mechanisms. In both cases, however, in normal animals, they seem to be intravascular. And since the symptoms of acute shock which can be produced in sensitized animals with moderate doses can also, though only occasionally, be produced in normal animals with larger doses, it is reasonable to suppose that the poisons produced intracellularly in the one may be similar to those produced intravascularly in the other. It does not seem likely that the specific circulating antibodies are in any way sources of increased injury to an animal spontaneously infected with bacteria. If sufficiently powerful at the beginning they may even prevent tissue injury, first by increasing phagocytosis, then by producing intravascular agglutination, and finally, as indicated by our experiments, even by removing a part of the antigen from possible reaction with the cell, though in this last respect our experiments indicate that they functionate imperfectly. It is more probable that their chief protective action to the sensitized body lies in removing the whole bacteria from the possibility of intravascular disintegration, which, as we have shown, is prerequisite to anaphylactic injury of the tissues of the host. We would tentatively summarize our opinion as to the occurrences in the typhoid-infected body as follows: Early injury is probably due to disintegration of part of the bacteria in the course of which albumose-like bodies are liberated, and, following which, intravascular reactions result in the formation of toxic substances, perhaps by some form of proteolysis. Since the accumulation of bacteria during these stages is relatively slight, this form of injury probably plays little part in producing symptoms. Indeed, the experiment by which acute injury is produced in the normal guinea pig by the sudden injection of several times the lethal dose of partly dissolved bacteria, finds no analogy in the spontaneously diseased body. At this time the tissues are not sensitive, but as antigen absorption progresses and the tissues are stimulated to react, sensitiveness develops, which renders them much more delicately amenable to injury by direct reaction with even small amounts of dissolved but otherwise unaltered antigen. This process is directly counteracted by circulating antibodies which tend to remove the bacteria from the possibility of yielding their antigen to solution by agglutinating them, aiding phagocytosis, and to a slight extent even neutralizing dissolved antigen. It seems likely, therefore, that the symptoms which appear as the incubation time ends are largely those due to cellular sensitization which probably begins before any considerable amount of circulatory antibodies is present. The circulating antibodies would seem to have little or nothing to do with intravascular injury, the ferments responsible for this, however much it may occur, probably consisting of the non-specific proteases studied in this connection by Jobling. Finally it appears that highly sensitized animals are more easily killed by typhoid antigen than are normal animals, provided they do not dispose over unusually large amounts of circulating antibodies. Cure would consist of a gradual checking of growth and final destruction of the bacteria, and the consequent cessation of antigen liberation, but delicate hypersusceptibility would probably persist for some time after cure and immunity have been established. Just what the relation between tissue hypersusceptibility and immunity is remains a problem for further study.     

Differential Effects of Obesity,Hyperlipidaemia, Dietary Intake and Physical Inactivity on Type I versus Type IV Allergies

Background: Alongside metabolic diseases (esp. obesity), allergic disorders are becoming increasingly prevalent. Since both obesity and allergies are highly impacted by environmental determinants, with this study we assessed the potential link between metabolic implications and two distinct types of allergies. Methods: Using cross-sectional data from the German FoCus cohort, n = 385 allergy cases, either hay fever (=type I allergy, n = 183) or contact allergy (=type IV allergy, n = 202) were compared to age- and sex-matched healthy control subjects (1:1 ratio, in total n = 770) regarding their metabolic phenotype, diet, physical activity, sleep, gut microbial composition, and serum metabolite profile using suitable BMI-adjusted models. Results: Obesity and metabolic alterations were found significantly more prevalent in subjects with allergies. In fact, this relation was more pronounced in contact allergy than hay fever. Subsequent BMI-adjusted analysis reveals particular importance of co-occurring hyperlipidaemia for both allergy types. For contact allergy, we revealed a strong association to the dietary intake of poly-unsaturated fatty acids, particularly α-linolenic acid, as well as the enrichment of the corresponding metabolic pathway. For hay fever, there were no major associations to the diet but to a lower physical activity level, shorter duration of sleep, and an altered gut microbial composition. Finally, genetic predisposition for hyperlipidaemia was associated to both contact allergy and hay fever. Conclusions: Reflected by higher allergy prevalence, our findings indicate an impaired immune response in obesity and hyperlipidaemia, which is differentially regulated in type I and type IV allergies by an unfavourable lifestyle constellation and subsequent microbial and metabolic dysfunctions.     

Arsenic methylation and skin cancer risk in southwestern Taiwan

Arsenic is a known carcinogen, but data are especially lacking on the health effects of low-level exposure, and on the health significance of methylation ability. We conducted a case-control study (76 cases and 224 controls from 1996 to 1999) in southwestern Taiwan to explore the association among primary and secondary arsenic methylation index (PMI and SMI, respectively), cumulative arsenic exposure (CAE), and the risk of skin cancer. As compared with the controls, the skin cancer group reported more sun exposure (P = 0.02) and had a lower BMI (P = 0.03), as well as lower education level (P = 0.01). Skin cancer patients and controls were similar with regard to age, gender, smoking and alcohol consumption. Given a low SMI (< or = 5), CAE > 15 mg/L-year was associated with an increased risk of skin cancer (OR, 7.48; 95% CI, 1.65-33.99) compared to a CAE < or = 2 mg/L-year. Given the same level of PMI, SMI, and CAE, men had a higher risk of skin cancer (OR, 4.04; 95% CI, 1.46-11.22) when compared to women. Subjects with low SMI and high CAE have a substantially increased risk of skin cancer. Males in all strata of arsenic exposure and methylation ability had a higher risk of skin cancer than women.     

The functional dissociation of posterior parietal regions during multimodal memory formation

The incidental acquisition of multimodal associations is a key memory function for everyday life. While the posterior parietal cortex has been frequently shown to be involved for these memory functions, ventral and dorsal regions revealed differences in their functional recruitment and the precise difference in multimodal memory processing with respect to the associative process has not been differentiated. Using an incidental multimodal learning task, we isolated the associative process during multimodal learning and recollection. The result of the present functional magnetic resonance imaging (fMRI) study demonstrated that during both learning and recollection a clear functional differentiation between ventral and dorsal posterior parietal regions was found and can be related directly to the associative process. The recruitment of a ventral region, the angular gyrus, was specific for learning and recollection of multimodal associations. In contrast, a dorsal region, the superior parietal lobule, could be attributed to memory guided attentional processing. Independent of the memory stage, we assumed a general role for the angular gyrus in the generation of associative representations and updating of fixed association, episodic memory.