Survival after peptic ulcer perforation: A time trend analysis

The survival of 1098 patients with ulcer perforation in Norway during the period 1952–1990 was compared with expected survival. Cox regression models incorporating population mortality rates, were used to analyse effects of sex, age, year of birth, and year at risk on excess mortality. Survival was lower in patients than in the general population through a follow-up period of 38 years. Relative survival was lower in women as compared to men, due to more delayed treatment. Long-term survival was lower after praepyloric perforations than after the other perforation types. Relative survival was higher in patients treated 1952–1970 than in those treated more recently. However, adjustment for year of birth revealed a decline in short-term mortality with calendar time, which is in accordance with improved management during the study period. Relative mortality, particularly long-term mortality, was higher in younger birth cohorts, suggesting a shift towards more serious etiologies.     

Update on adverse drug events associated with parenteral iron.

BACKGROUND: We previously compared the safety profile of three formulations of intravenous iron used during 1998-2000 and found higher rates of adverse drug events (ADEs) associated with the use of higher molecular weight iron dextran and sodium ferric gluconate complex compared with lower molecular weight iron dextran. Since that time, iron sucrose has become widely available and clinicians have gained additional experience with sodium ferric gluconate complex. METHODS: We obtained data from the United States Food and Drug Administration (FDA) on ADEs attributed to the provision of four formulations of intravenous iron during 2001-2003, including higher and lower molecular weight iron dextran, sodium ferric gluconate complex and iron sucrose. We estimated the odds of intravenous iron-related ADEs using 2 x 2 tables and the chi(2) test. RESULTS: The total number of reported parenteral iron-related ADEs was 1141 among approximately 30,063,800 doses administered, yielding a rate of 3.8 x 10(-5), or roughly 38 per million. Eleven individuals died in association with the ADE. Relative to lower molecular weight iron dextran, total and life-threatening ADEs were significantly more frequent among recipients of higher molecular weight iron dextran and significantly less frequent among recipients of sodium ferric gluconate complex and iron sucrose. The absolute rates of life-threatening ADEs were 0.6, 0.9, 3.3 and 11.3 per million for iron sucrose, sodium ferric gluconate complex, lower molecular weight iron dextran and higher molecular weight iron dextran, respectively. Based on differences in the average wholesale price of iron sucrose and lower molecular weight iron dextran in the US, the cost to prevent one life-threatening ADE related to the use of lower molecular weight iron dextran was estimated to be 5.0-7.8 million dollars. The cost to prevent one lower molecular weight iron dextran-related death was estimated to be 33 million dollars. CONCLUSIONS: The frequency of intravenous iron-related ADEs reported to the FDA has decreased, and overall, the rates are extremely low. This is the fourth report suggesting increased risks associated with the provision of higher molecular weight iron dextran. Life-threatening and other ADEs appear to be lower with the use of non-dextran iron formulations, although the cost per ADE prevented is extremely high.     

Structural Characterization of Persistent Tympanic Membrane Perforations in Man

In the present structural study the authors investigated the border of permanent tympanic membrane (TM) perforations in patients selected for myringoplasty. Furthermore, a panel of monoclonal antibody markers that recognize different epitopes within glycosaminoglycans as well as antibodies to epidermal growth factor and fibronectin were applied to the sections. In half of the specimens the epithelial junction ended at the inside of the perforation border, whereas in the other half it was located at the perforation border itself. In the junctional area the keratinocytes were covered by a thick keratin layer which protruded as a spur centripetally in order to bridge the perforation. Epidermal cells formed papillae and contained remnants of keratinocyte nuclei that showed similarities to those of the skin in inflammatory conditions. The connective tissue layer was fibrous and showed areas containing sclerotic plaques. The inner epithelium of the TM had abundant ciliae, thus supporting the concept that cells of the mucosal lining of the TM are able to differentiate in inflammatory conditions into ciliated cells and secretory cells. The immunoreactivity of hyaluronan and other glycosaminoglycans, the immunoreactivity of epidermal growth factor, and the immunoreactivity of fibronectin, all of which are known to occur in healing wounds, were only scantily demonstrated; this could be one reason for the arrested healing and a reason why the natural drive to complete a mature closure is abandoned.     

Regio-Selectivity of Purified Forms of Rabbit Liver Microsomal Cytochrome P-450 in the Metabolism of Benzo(a)pyrene,n-Hexane and 7-Ethoxyresorufin

Abstract: The specificity of electrophoretically homogeneous preparations of rabbit liver microsomal cytochrome P-450lm _2–4 towards oxygenation of n-hexane, 7-ethoxyresorufin and benzo(a)pyrene was examined using a reconstituted system consisting of cytochrome P-450, NADPH-cytochrome P-450 reductase and dilauroylphosphatidylcholine. Epoxide hydrase was included when benzo(a)pyrene was used as substrate. Cytochrome P-450lm ₂ was most active in n-hexane and benzo(a)pyrene oxygenation especially with regard to the formation of 2-hexanol, B(a)P-4,5-dihydrodiol and B(a)P-phenol metabolites. 7-Ethoxyresorufin was, however, a very poor substrate for cytochrome P-450lm ₂. Cytochrome P-450lm ₃ had less activity towards the investigated substrates while cytochrome P-450lm ₄ preferentially formed 2- and 3-hexanol, resorufin and B(a)P-9,10-dihydrodiol. Cytochrome P-450lm ₄ isolated after pretreatment with 3-methylcholanthrene or pheno-barbital showed roughly the same characteristics except in the formation of 1-hexanol where cytochrome P-450lm ₄ isolated after phenobarbital treatment was the most effective. The formation of B(a)P-4,5- and ?9,10-dihydrodiols was greatly increased by incorporation of epoxide hydrase. Our results indicate a certain specificity of the different forms of cytochrome P-450 in the liver microsomes although some overlap in activities was observed.     

Further results on the non-parametric linear regression model in survival analysis

This paper gives further developments of a non-parametric linear regression model in survival analysis. Three subjects are studied. First, martingale residuals, originally developed for the Cox model, are introduced for our linear model. Their theory is developed and they are shown to be useful for judging goodness of fit. The second focus of the paper is on the use of bootstrap replications to judge which features of the cumulative regression plots are likely to reflect real phenomena and not merely random variation. In particular, this is applied to judging whether the effect of a covariate disappears over time, a problem for which no formal test exists. The third subject is density type, or kernel, estimation of the regression functions themselves. This might give more direct information than the cumulative plots. The approaches are illustrated by data from a clinical trial of carcinoma of the oropharynx, and by survival times of grafts in renal patients.     

Comparison of protein expression in plasma from nonylphenol and bisphenol A-exposed Atlantic cod (Gadus morhua) and turbot (Scophthalmus maximus) by use of SELDI-TOF

The overall objective of this study was to compare the expression of plasma proteins in juvenile cod and turbot after a 3 week exposure to two different chemicals known to be estrogenic: 4-nonylphenol (NP, 29 microg/L) and bisphenol A (BPA, 59 microg/L). ProteinChip) array technology in combination with surfaced enhanced laser desorption ionisation-time of flight (SELDI-TOF) was used to investigate general responses in plasma proteins. In addition, an indirect enzyme-linked immunosorbent assay (ELISA) was used to analyse two specific biomarkers of estrogenic exposure, vitellogenin (Vtg) and zona radiata protein (Zrp) in plasma. Both methods revealed clear species specific responses. In cod, 67% of significantly altered proteins showed the same response (up or down regulated) in NP and BPA exposed animals (males and females combined). The rest were either specific to NP (10%), BPA (19%) or they showed opposite responses to the two chemicals (4%). In contrast, only 20% of significantly altered proteins were common for NP and BPA exposed turbot: 60% were altered only in NP and 17% only in BPA. Furthermore, in BPA exposed cod, 77% of the responses were common for male and females, whereas turbot showed only 21% similarity for the two genders. However, NP exposed male and female turbot showed 88% similarity in responses. As gender was not determined in NP exposed cod, gender specific responses could not be determined. ELISA results supported that cod responded clearly to both chemicals as a large increase was observed in Vtg and Zrp levels. Turbot responded strongly to NP, but seemed only slightly affected by BPA. Overall, the results indicated that cod are more sensitive or respond with less specificity to estrogenic chemicals than turbot. The relatively large degree of common responses in NP and BPA exposed cod may indicate that in cod BPA have similar mode of action as NP. Generally, the results show the potential of SELDI-TOF as a tool for comparing multiple responses, and for identifying exposure as well as gender specific responses.     

Evidence-based policy? The use of mobile phones in hospital

BACKGROUND: Evidence-based policies have become increasingly accepted in clinical practice. However, policies on many of the non-clinical activities that take place in health care facilities may be less frequently evidence based. METHODS: We carried out a review of literature on safety of mobile phones in hospitals and survey of practice in selected European countries. RESULTS: When first evidence on the dangers of electronic interference associated with mobile phones appeared in the 1990s, hospitals in many countries introduced complete bans on mobile phones. Yet a review of recent evidence suggests that there is no significant risk from using mobile phones in hospitals as long as they are more than a metre away from sensitive equipment, whereas the risk to the most modern equipment is even less. With the technological evolution of mobile phones, the residual risk of interference appears to be minimal and controllable. Although some countries are reluctant to relax regulation, others now limit bans to areas in which sensitive equipment is used and some discourage the use of mobile phones on the grounds of noise exposure. CONCLUSION: With new technology on the doorstep, the potential benefits and risks associated with mobile phones should be examined explicitly in the light of the evidence.     

Contrast-enhanced and targeted ultrasound

Ultrasonic imaging is becoming the most popular medical imaging modality,owing to the low price per examination and its safety.However,blood is a poor scatterer of ultrasound waves at clinical diagnostic transmit frequencies.For perfusion imaging,markers have been designed to enhance the contrast in B-mode imaging.These so-called ultrasound contrast agents consist of microscopically small gas bubbles encapsulated in biodegradable shells.In this review,the physical principles of ultrasound contrast agent mic...