The risk of a diagnosis of cancer after primary deep venous thrombosis or pulmonary embolism

BACKGROUND: Several small studies have indicated an association between deep venous thrombosis or pulmonary embolism and a subsequent diagnosis of cancer, but the subject is controversial. METHODS: We conducted a nationwide study of a cohort of patients with deep venous thrombosis or pulmonary embolism that was drawn from the Danish National Registry of Patients for the years 1977 through 1992. The occurrence of cancer in the cohort was determined by linkage to the Danish Cancer Registry. The expected number of cancer cases was estimated on the basis of national age-, sex-, and site-specific incidence rates. RESULTS: A total of 15,348 patients with deep venous thrombosis and 11,305 patients with pulmonary embolism were identified. We observed 1737 cases of cancer in the cohort with deep venous thrombosis, as compared with 1372 expected cases (standardized incidence ratio, 1.3; 95 percent confidence interval, 1.21 to 1.33). Among the patients with pulmonary embolism, the standardized incidence ratio was 1.3, with a 95 percent confidence interval of 1.22 to 1.41. The risk was substantially elevated only during the first six months of follow-up and declined rapidly thereafter to a constant level slightly above 1.0 one year after the thrombotic event. Forty percent of the patients given a diagnosis of cancer within one year after hospitalization for thromboembolism had distant metastases at the time of the diagnosis of cancer. There were strong associations with several cancers, most pronounced for those of the pancreas, ovary, liver (primary hepatic cancer), and brain. CONCLUSIONS: An aggressive search for a hidden cancer in a patient with a primary deep venous thrombosis or pulmonary embolism is not warranted.     

Relapsing polychondritis

Streptococcus pneumoniae is a relatively uncommon cause of septic arthritis, and Infection of the sacroiliac joint by this organism has been rarely described. We present such a case.     

The collagenolytic activity of cathepsin K is unique among mammalian proteinases

Type I collagen fibers account for 90% of the organic matrix of bone. The degradation of this collagen is a major event during bone resorption, but its mechanism is unknown. A series of data obtained in biological models strongly suggests that the recently discovered cysteine proteinase cathepsin K plays a key role in bone resorption. Little is known, however, about the actual action of cathepsin K on type I collagen. Here, we show that the activity of cathepsin K alone is sufficient to dissolve completely insoluble collagen of adult human cortical bone. We found that the collagenolytic activity of cathepsin K is directed both outside the helical region of the molecule, i.e. the typical activity of cysteine proteinases, and at various sites inside the helical region, hitherto believed to resist all mammalian proteinases but the collagenases of the matrix metalloproteinase family and the neutrophil elastase. This property of cathepsin K is unique among mammalian proteinases and is reminiscent of bacterial collagenases. It is likely to be responsible for the key role of cathepsin K in bone resorption.     

The interaction of lung annexin I with phospholipid monolayers at the air/water interface

The carcinogenicity of 1,2-dibromoethane (ethylene dibromide; EDB) was investigated in the Japanese medaka (Oryzias latipes), a small fish species. EDB was administered in water continuously for 97 days to a low concentration group, for 73 days to an intermediate concentration group, and intermittently for 24 h once each week over 97 days to a high concentration group. Medaka were 7 days old at the beginning of the tests. Mean measured EDB concentrations in the ambient water were 0.13 mg l-1, 6.20 mg l-1, and 18.58 mg l-1 in the low, intermediate, and high concentration groups, respectively. Two control groups, one inside and one outside the exposure apparatus, were used. Samples were examined histologically at 24, 36, and 58 weeks from the beginning of the tests. EDB was clearly carcinogenic to medaka in the intermediate and high concentration groups causing (1) hepatocellular adenomas and carcinomas, (2) cholangiomas, (3) chloangiocarcinomas, and (4) gall bladder papillary adenomas and adenocarcinomas. In separate studies, medaka exposed to 1.0 mg l-1 EDB for 2 to 5 weeks had elevated hepatic glutathione S-transferase activities, possibly indicating induction of a pathway that forms the reactive metabolite of EDB in mammals. SDS-PAGE of hepatic cytosolic fractions of EDB-exposed medaka showed a pronounced increase in a band at 26,000 Da, the expected position for GSH-S-transferase. Although little is known about EDB's mechanisms of action, medaka appear exceptionally sensitive to the carcinogenic effects of EDB and could serve as a model test species for studying similar compounds.     

The LETR-Principle: a novel method to assess electrode-tissue contact in radiofrequency ablation

INTRODUCTION: Stable electrode-tissue contact is crucial for successful radiofrequency ablation of cardiac tachyarrhythmias. In this in vitro study, a custom-made radiofrequency generator was used to evaluate the correlation between tip temperature response to a minimal radiofrequency power delivery (Low Energy Temperature Response: LETR-Principle) and electrode-tissue contact as well as lesion size. METHODS AND RESULTS: A battery-powered radiofrequency generator (LETR-Box, 500 kHz, 0.1 to 0.3 W) could measure the temperature increase at the tip electrode with 0.01 degrees C accuracy. The device was tested in vitro using isolated porcine ventricular tissue. For various electrode-tissue settings (i.e., 0 to 0.89 N contact force), the temperature increase (deltaT) due to 0.1-W power delivery for 10 seconds was recorded. Subsequently, for the same electrode-tissue contact, a temperature-controlled radiofrequency ablation was performed (70 degrees C target temperature, 50-W maximum output, 30 sec). Thereafter, the lesion size was measured histologically. To prove the safety of the applied LETR-Principle, the tissue was inspected microscopically after continuous radiofrequency power delivery of 0.3 W for 1 hour with high contact pressure (1.33 N). The delivery of 0.1-W radiofrequency power resulted in an average deltaT of 0.18 degrees +/- 0.13 degrees C. During temperature-controlled radiofrequency ablation, the tip temperature was 59 degrees +/- 8.5 degrees C, resulting in a lesion depth of 4.8+/-0.6 mm. The correlation coefficient between deltaT and contact force was 0.97 and 0.81, respectively, for lesion depth. No lesion was microscopically visible after power delivery of 0.3 W for 1 hour with 1.33 N contact pressure. CONCLUSION: The LETR-Principle safely indicates electrode-tissue contact and lesion depth under in vitro conditions and can be useful for catheter positioning during radiofrequency ablation procedures.     

Effect of water diuresis and water restriction on expression of HSPs-27, -60 and -70 in rat kidney

Expression of HSP-27, HSP-60 and HSP-70 was estimated in the cortex, outer medulla and inner medulla (papilla) of rats undergoing water diuresis or water restriction for two days. The mRNAs for HSP-27 and HSP-60 in renal papilla were two- to threefold greater in rats during water restriction than in those excreting a dilute urine, but levels of mRNA for HSP-70 were not reduced by water diuresis and Western analysis for HSP-70 protein showed no difference between water-loaded and water-restricted animals.     

Comparison of blood pressure and angiotensin responses to the renin inhibitor Ro 42-5892 and the angiotensin converting enzyme inhibitor enalapril in essential hypertension

OBJECTIVE: To compare the responses of angiotensin II (Ang II) and blood pressure to the renin inhibitor Ro 42-5892 and the angiotensin converting enzyme (ACE) inhibitor enalapril. SUBJECTS: Eight non-sodium-restricted patients with mild-to-moderate essential hypertension. DESIGN: A single-blind crossover study. Ro 42-5892 (600 mg orally, once a day) and enalapril (20 mg orally, once a day) were given for 8 days before detailed investigations were carried out. METHODS: Ambulatory blood pressure was measured directly for 24 h by the Oxford technique on three occasions. Off-treatment and on day 8 of treatment with Ro 42-5892 and with enalapril. Ang II was measured by radioimmunoassay after separation by high-performance liquid chromatography. RESULTS: Plasma renin activity and Ang II were lowered by 83% [95% confidence interval (CI) 61-105] and 68% (95% CI 49-87), respectively, 0.5-1 h after Ro 42-5892, but after only 3 h values had returned to baseline. Unlike this rapid and short-term suppression of Ang II, the maximal antihypertensive response to Ro 42-5892 (fall in blood pressure 12.9/9.0 mmHg) occurred only after 6 h. Blood pressure returned to baseline after 8 h. In response to enalapril, Ang II was maximally suppressed by 63% (95% CI 32-94) after 2 h and by 83% (95% CI 76-90) after 8 h. Despite early maximal Ang II suppression, the maximal antihypertensive response to enalapril occurred only after 12 h (fall in blood pressure 25.3/16.3 mmHg). With this compound a significant antihypertensive effect was still present 24 h after dosing. CONCLUSIONS: Compared with enalapril at 20 mg once a day, repeated oral administration of a single dose of Ro 42-5892 at 600 mg caused only short-term suppression of Ang II and blood pressure. Suppression of Ang II and reduction in blood pressure were temporally dissociated, both with the ACE inhibitor and the renin inhibitor. This implies that the blood pressure lowering effect of these inhibitors is caused partly by Ang II suppression outside the circulation.     

Effect of hydroxyapatite particle size on myoblasts and fibroblasts

After surgery, the bone and soft tissues around integrated biomaterials can be adversely affected by implant-related factors acting over a period of years. However, few studies have directly addressed the effects upon the adjacent soft tissue. The present study was designed to test the biological effects of various sized hydroxyapatite (HA) particles on myoblasts and fibroblasts. Both the myoblasts and fibroblasts were mixed in in vitro culture with 0.1% (1 mg ml(-1)) of various sized HA particles (0.5-3.0, 37-63, 177-250, 420-841 microm) for 1 h, 3 h, 1 day, 3 days and 7 days to test their effects on the cell culture. The results show that adding HA particles into a cell culture can decrease the cell count significantly. The transforming growth factor-beta1 (TGF-beta1) concentrations in the culture medium decreased significantly on addition of HA particles. When calculated as a ratio to the cell number, the TGF-beta1 titre increased most significantly in the groups of medium-sized particles. The prostaglandin E2 (PGE2) concentrations in the medium increased significantly. The changes in TGF-beta1 and PGE2 concentrations with the smallest particles were most significant and persisted longer. The inhibitory effects of the HA particles on the cell culture were mediated by the increased synthesis of PGE2. Caution should be exercised before considering the use of an HA product which could easily break down into a fine powder.     

Functional evaluation of the ligaments at the acromioclavicular joint during anteroposterior and superoinferior translation

We examined the anatomy and measured the in situ force in ligaments at the acromioclavicular joint using a universal force-moment sensor. The in situ force in the coracoacromial, conoid, trapezoid, superior acromioclavicular capsular, and inferior acromioclavicular capsular ligaments of 10 fresh-frozen cadaveric shoulders was determined for a load of 70 N applied to the clavicle in anteroposterior and superoinferior directions. The lengths of the conoid and trapezoid ligaments were found to be 15.1 +/- 4.1 and 11.5 +/- 2.2 mm, respectively; the widths of the conoid and trapezoid ligaments were 10.7 +/- 1.5 and 11.0 +/- 2.8 mm, respectively. The in situ force of the trapezoid (42.9 +/- 15.4 N) was significantly greater than that for the other ligaments during posterior displacement. Otherwise, no statistically significant differences could be found between any of the in situ forces in each ligament during all other motions examined. During anterior displacement, the inferior acromioclavicular capsular ligament appeared to be the major restraint. The trapezoid ligament was the primary restraint during posterior displacement and provided 55.8% +/- 20.0% of the resisting force. Our results suggest that the coracoclavicular and other acromioclavicular joint capsular ligaments should be considered for reconstruction to restore normal joint function, especially in the anterior, posterior, and superior directions.