Breast cancer survival is associated with telomere length in peripheral blood cells

Telomeres are essential for maintaining chromosomal stability. Previous studies have indicated that individuals with shorter blood telomeres may be at higher risk of developing various types of cancer, such as in lung, bladder, and kidney. We have analyzed relative telomere length (RTL) of peripheral blood cells in relation to breast cancer incidence and prognosis. The study included 265 newly diagnosed breast cancer patients and 446 female controls. RTL was measured by real-time PCR, and our results show that the patient group displayed significantly longer telomeres compared with controls (P < 0.001). Age-adjusted odds ratios (OR) for breast cancer risk increased with increasing telomere length, with a maximal OR of 5.17 [95% confidence interval (95% CI), 3.09-8.64] for the quartile with the longest telomeres. Furthermore, RTL carried prognostic information for patients with advanced disease. Node positive (N+) patients with short telomeres (16 mm (median tumor diameter), short telomeres were associated with a significantly better outcome than longer telomeres (P = 0.006). Cox regression analysis showed that long RTL was a significant independent negative prognostic factor (hazards ratio, 2.92; 95% CI, 1.33-6.39; P = 0.007). Our results indicate that blood RTL may serve as a prognostic indicator in breast cancer patients with advanced disease.     

Apheresis as therapy for patients with severe sepsis and multiorgan dysfunction syndrome.

Progressive multiorgan dysfunction syndrome may occur in the course of sepsis and septic shock as well as after various intoxications, pancreatitis, crush injuries, and major surgery. Despite conventional intensive care therapies, the prognosis in these patients is still poor. Apheresis, which uses more selective adsorption techniques, can lower the extent of toxins and cytokines in blood. This is achieved in clinical practice by, e.g., using polymyxin B as adsorbent. Although significantly lowered, the mortality is still about 50% with this technique. By unselective plasma exchange, the mortality is reduced down to 20 to 40%. A controlled and randomized study has shown a significant benefit. The centrifugation technique may be favorable over plasma filtration. Not only removal but also replacement with plasma seems important. In the future, probably selective techniques will be used in the early stages of sepsis while unselective plasma exchange may be useful in a disseminated situation.     

No increase in the prevalence of known diabetes between 1986 and 1999 in subjects 25-64 years of age in northern Sweden.

AIMS: A global increase in diabetes is predicted due to higher body weight and less physical activity. Over the period 1986-1999, the body mass index (BMI) of the adult population of northern Sweden increased from 25.3 to 26.2 and the prevalence of obesity (BMI > or = 30) from 11% to 15%, although this was more distal than central adiposity. Our hypothesis was that this would lead to a higher prevalence of diabetes. METHODS: Four population surveys with new and independent cohorts of 2000 invited subjects, 25-64 years old, in 1986, 1990, 1994 and 1999. In the first three surveys an oral glucose tolerance test was carried out in 47%. RESULTS: Over the time period 1986-1999 there was no increase in the prevalence of known diabetes. No trends were noted in the finding of previously undiagnosed diabetes or impaired glucose tolerance over the period 1986-1994, although the confidence intervals are wide. Fasting, but not post-load, glucose levels increased with 0.040 mmol/year (95% CI 0.026; 0.055) in men and 0.033 mmol/year (0.023; 0.044) in women. CONCLUSION: In spite of a marked increase in BMI, we found no increased prevalence of known diabetes over a 13-year observation period, although our data cannot exclude minor increases in undiagnosed diabetes. The development of more distal than abdominal obesity, a diet with less saturated fat and lower glycaemic index and fewer regular smokers in the population may contribute to this. The effects of obesity may thus be attenuated by other secular trends in society and highlight potential ways of curbing the worldwide increase in diabetes.     

Chlamydia pneumoniae antibodies and high lipoprotein(a) levels do not predict ischemic cerebral infarctions. Results from a nested case-control study in Northern Sweden.

BACKGROUND AND PURPOSE: An association between high lipoprotein(a) [Lp(a)] levels and positive Chlamydia pneumoniae IgG titers in coronary artery disease has been described. The possibility of predicting ischemic stroke by measurements of plasma Lp(a) and C pneumoniae antibodies was investigated. METHODS: This incident case-control study included 101 case subjects (cases) who had suffered ischemic cerebral infarctions and 201 matched control subjects (controls). The study population was nested within the V?sterbotten Intervention Program or the WHO MONICA project. Plasma samples were measured for C pneumoniae-specific IgG and IgA antibodies and Lp(a). RESULTS: A significantly higher mean Lp(a) level was found in female cases than in female controls. However, plasma Lp(a) was unable to predict ischemic cerebral infarctions in either women or men. The proportion of individuals with positive C pneumoniae-specific IgG or IgA titers did not differ between cases and controls. Antibody titers were unable to predict a future stroke. The proportion of individuals with a positive C pneumoniae IgG titer in combination with a high Lp(a) level did not differ significantly between cases and controls. CONCLUSIONS: These data suggest that there is no association between baseline plasma Lp(a) levels, presence of C pneumoniae antibodies, and future ischemic cerebral infarctions. Furthermore, no evidence of an interactive effect between high Lp(a) levels and C pneumoniae IgG titers was found. However, selection bias and a recent C pneumoniae epidemic may have influenced the results.     

The Presence of Superantigens and Complex Host Responses in Severe Sepsis May Need a Broad Therapeutic Approach

Abstract: Patients with sepsis can progress into septic shock, disseminated intravascular coagulation, and multiorgan dysfunction syndrome. Various materials secreted by or released from microorganisms such as bacteria initiate these processes. In some bacteria, certain antigens and toxins may cause a 100‐fold greater or supernormal activation of monocytes and T lymphocytes, leading to activation of the cascade systems in the host. This can explain the extremely rapid progress of the sepsis into septic shock seen in some patients. In Group A streptococci, more than 100 different toxins have been identified, about 5 of which (superantigens) cause an extremely fast immunological response. Because the toxins and antigens can activate so many different cascade systems in the host, the clinical picture is extremely complex, and little benefit is derived from therapy, which interferes with only 1 or 2 of the parameters in the patient with sepsis. Instead, reversal of the septic shock requires the removal or inhibition of several toxins or substances activating the cascade systems. A broader therapeutic approach may be the use of apheresis (plasma exchange).     

Ischemic stroke and shift work

OBJECTIVES: This study analyzed the potential association between shift work and ischemic stroke. METHODS: The analysis was carried out using a nested case-control study consisting of 138 shift workers and 469 day workers from the register of the Northern Sweden Monitoring of Trends and Determinants in Cardiovascular Diseases (MONICA) study and the V?sterbotten Intervention Programme. Logistic regression analysis was used to analyze the risk estimate for day workers in a comparison with shift workers and the risk of ischemic stroke. RESULTS: The crude odds ratio for shift workers' risk of experiencing an ischemic stroke was 1.0 (95% confidence interval 0.6-1.8) for both the men and the women. The risk estimates were consistent despite the introduction of several recognized risk factors for ischemic stroke in the logistic regression models. CONCLUSIONS: In the present study, none of the findings indicated a higher risk of shift workers undergoing an ischemic stroke than day workers.     

The Role of EUTox in Uremic Toxin Research

In this publication, we review the activities of the European Uremic Toxin Work Group (EUTox) in the field of uremic toxin research. Founded in 1999 under the umbrella of the European Society of Artificial Organs (ESAO), and active since 2000, this group focuses essentially on questions related to solute retention and removal during chronic kidney disease, and on the deleterious impact of those solutes on biological/biochemical systems. As of January 1, 2009, the group had met 28 times; it organized the third meeting, "Uremic Toxins in Cardiovascular Disease," which took place in October 2008 in Amiens, France. The current group is composed of 25 members belonging to 23 European research institutions. As of November 1, 2008, in total 69 papers had been published to which at least two different research groups belonging to EUTox have contributed in a collaborative effort. Of these, 40 papers were on original research and eight were specific EUTox reviews or position statements. A website ( http://www.eutox.info ) summarizes all relevant information concerning the work group. EUTox also developed an interactive uremic toxin database, where concentrations of known toxins are displayed, to be used by researchers in the field. In the future, EUTox intends to continue its focus on bench to bedside research with specific consideration of proteomics, metabonomics, secretomics, and genomics.     

Citalopram pharmacokinetics in patients with chronic renal failure and the effect of haemodialysis

OBJECTIVE: To study the effects of severe renal failure and haemodialysis on the pharmacokinetics of citalopram. METHODS: Four patients with renal failure undergoing haemodialysis and eight healthy controls were given a single dose of citalopram. The concentrations of citalopram and its metabolites desmethylcitalopram and didesmethylcitalopram were measured in serum and urine. On a different day, the four patients undergoing haemodialysis were given another single dose of citalopram, and the drug concentrations were measured in serum from the artery leading to the dialyser and in the dialysate. In addition, one anuric patient treated with citalopram on a regular basis was included in the study. RESULTS: There were no significant differences between the two groups in any of the pharmacokinetic parameters with the exception of the renal clearance of citalopram, which was significantly lower in the renal failure group than in the control group (1.70 ml/min versus 66.2 ml/min, P<0.001). Oral clearance of citalopram was almost identical in the two groups (452 ml/min versus 456 ml/min). The process of haemodialysis cleared about 1% of the dose as citalopram and 1% as desmethylcitalopram only. CONCLUSION: Severe renal failure does not affect the pharmacokinetics of citalopram and modification of the usual citalopram dose does thus not seem to be necessary. The contribution of haemodialysis to the total elimination of citalopram is negligible.