Low HDL-C predicts the onset of transplant vasculopathy in pediatric cardiac recipients on pravastatin therapy

The levels and protein/lipid compositions of major lipoprotein particles of 19 pediatric cardiac transplant recipients (4-18 yr of age) were studied in this prospective, open clinical follow-up study before and at one yr of pravastatin therapy (10 mg/day). The recipients were grouped into those with (n = 6; group A) and those without (n = 13; group B) angiographically detectable vasculopathy. Twenty-one pediatric non-transplant controls were studied at baseline. At baseline, the group A recipients had 29% lower HDL-C concentrations (p = 0.031) and 29% higher apoB-100/apoA-I ratios (p = 0.034) than the group B recipients. At one yr of pravastatin, the respective figures were 29% (p = 0.013) and 33% (p = 0.005). Compared with the healthy pediatric controls, the transplant recipients had significantly higher serum TG before pravastatin [median (range): 1.3 mmol/L (0.6-3.2) vs. 0.7 mmol/L (0.3-2.4), p = 0.0002] and at one yr [1.3 mmol/L (0.5-3.5) vs. 0.7 mmol/L (0.3-2.4), p = 0.0004]. The baseline apoB-100/apoA1 ratios of the recipients were 33% higher (p = 0.005). In conclusion, low HDL-C and high apoB-100/apoA-I ratio were associated with angiographically detectable vasculopathy. Even though pravastatin effectively lowered the TC and LDL-C and improved compositional properties of LDL and HDL(2) particles, it failed to normalize the elevated TG and, in some patients, to prevent the progression of transplant vasculopathy.     

Cancer of the mouth and pharynx, occupation and exposure to chemical agents in Finland [in 1971-95

The objective of this article was to find associations between cancer of the mouth and pharynx, occupation and chemical exposure. A cohort of Finns born between 1906 and 1945 was followed-up for 46.8 (21.5 in males and 25.3 in females) million person-years during 1971-95. Incident cases of cancer of the mouth and pharynx (n = 2,708) were identified in a record linkage with the Finnish Cancer Registry. The Census occupations in 1970 were converted to chemical exposures with a job-exposure matrix (FINJEM). Cumulative exposure (CE) was calculated as the product of prevalence, level and duration of the exposure. Standardized incidence ratio (SIR) was calculated for each of the 393 occupations, and for CE categories of the 43 chemical agents, using total Finnish population as reference. Relative risks (RR) comparing various CE-categories with unexposed ones were defined for selected agents by Poisson regression analysis. Elevated SIRs were observed among lawyers, authors, journalists, performing artists, musicians, electronics and telefitters, painters (building), building hands, dockers, unskilled labourers and hotel porters in males and private secretaries, dressmakers, shoemakers and cobblers, waiters, pursers and stewardesses in females. The multivariate analyses showed high RRs for high exposure to aliphatic and alicyclic hydrocarbons, pesticides and alcohol. In conclusion, occupations with high SIRs were mostly the ones with high consumption of alcohol. Exposure to solvents and possibly to pesticides, engine exhaust, textile dust and leather dust may increase the risk of cancer of mouth and pharynx.     

On the avoidability of breast cancer in industrialized societies: older mean age at first birth as an indicator of excess breast cancer risk

Background Breast cancer incidence continuous to increase. We examined at population level the association between the relative excess risk of breast cancer and previous age of mother at first birth. Method Incidence of breast cancer in 34 industrialized countries was obtained from the GLOBOCAN 2002 and SEER databases. Data on age of mother at first birth was collected through national statistics offices. National relative excess risk (RER) was calculated by subtracting the lowest age-specific incidence rate from the rate in each population, and dividing the difference by the latter. Results The national RER in 2002 correlated closely with a higher average age at first birth in 1972, 1982, 1992 and also 2002, Pearson correlation [r] being 0.83, 0.79, 0.72 and 0.61, respectively; P < 0.0001. RER of breast cancer in 2002 for those aged 15-44 years correlated closely with the mean age at first birth in 1982 and 1992 (r: 0.81 and 0.75; P < 0.0001), whereas RER for those aged 45-54 years correlated strongly with age at first birth in 1972 and 1982 (r: 0.81 and 0.76; P < 0.0001), and for those aged 55-64 years with age at first birth in 1972 (r: 0.77; P < 0.0001). Conclusions The rising age at first childbirth of mothers has been followed by marked increases in breast cancer incidence. Later age at first birth seems to characterize secular diffusion of 'modern' lifestyles with a potentially large impact on increased breast cancer risk, and hence should be accompanied by greater opportunities for prevention through modifiable risk factors.     

Statins and cancer: A systematic review and meta-analysis

BackgroundSystematic reviews on the association between statin therapy and cancer have focused on randomised trials without assessing the quality of evidence. We aimed to review the overall evidence taking study quality into consideration.MethodsPublications of original studies on the effect of statin treatment on cancer in adult patients were searched on MEDLINE, EMBASE and CENTRAL databases upto October 2007. Our search yielded 37 eligible original studies out of 3607 references. Five studies were additionally found through manual search. Thus, 42 studies were included in the analyses: 17 randomised controlled trials, 10 cohort studies, and 15 case-control studies.FindingsStatins had no effect on the overall incidence of cancer (median risk ratio (RR) 0.96, range 0.72 to 1.2), or on the incidence of lung (median RR 0.92, range 0.83 to 3.0), breast (median RR 1.04, range 0.74 to 19) or prostate cancer (median RR 0.96, range 0.33 to 1.7). They seemed to protect from stomach (median RR 0.59, range 0.40 to 0.88) and liver cancer (median RR 0.62, range 0.33 to 1.2), and from lymphoma (median RR 0.74, range 0.28 to 2.2). They increased the incidence of both melanoma (median RR 1.5, range 1.3 to 1.7) and non-melanoma skin cancer (median RR 1.6, range 1.2 to 2.2). The effect varied, yet inconsistently, by statin type. The median follow-up time was 4 years. The strength of evidence was mostly weak.InterpretationThe evidence suggests that statins do not have short-term effects on cancer risk. The evidence on potentially protective or harmful effects is inconclusive. High quality cohort studies with long follow-up are needed to resolve the issue.     

Delayed impairment of cerebral oxygenation after deep hypothermic circulatory arrest in children

Background. Clinical studies of deep hypothermic circulatory arrest (DHCA) have focused only on the immediate postoperative period. However, experimental findings suggest impairment of cerebral oxygenation at 2 to 8 hours after reperfusion.

Methods. In 10 children who had DHCA for heart operations, transcerebral differences of hemoglobin oxygen saturation and plasma hypoxanthine, xanthine, and lactoferrin concentrations were measured in concurrently obtained cerebral venous, arterial, and mixed venous samples up to 10 hours postoperatively.

Results. Compared with preoperative levels (57% ± 7%), cerebral venous oxygen saturation was not significantly reduced until 2 hours (44% ± 6%) and 6 hours (42% ± 5%) after DHCA (p < 0.05). A statistically significant transcerebral (ie, cerebral vein versus artery) concentration difference of hypoxanthine was observed at 30 minutes (3.6 ± 0.9 μmol/L), 1 hour (3.4 ± 1.1 μmol/L), and 2 hours (3.1 ± 0.8 μmol/L) after DHCA but not preoperatively (0.4 ± 0.2 μmol/L). A transcerebral concentration difference of lactoferrin occurred 30 minutes after DHCA (196 ± 70 μg/mL) but not preoperatively (16 ± 20 μg/mL).

Conclusions. Cerebral venous oxygen saturation of hemoglobin decreased as late as 2 to 6 hours after DHCA, in association with impaired cerebral energy status. Neutrophil activation in the cerebral circulation occurred 30 minutes after reperfusion.     

Laryngo-tracheal resections in the Nordic countries: an option for further centralization?

European Archives of Oto-Rhino-Laryngology - We aimed to obtain information on the number of Nordic centers performing tracheal resections, crico-tracheal resections, and laryngo-tracheal...     

Cytolytic Properties and Genome Analysis of Rigvir® Oncolytic Virotherapy Virus and Other Echovirus 7 Isolates

Rigvir^® is a cell-adapted, oncolytic virotherapy enterovirus, which derives from an echovirus 7 (E7) isolate. While it is claimed that Rigvir^® causes cytolytic infection in several cancer cell lines, there is little molecular evidence for its oncolytic and oncotropic potential. Previously, we genome-sequenced Rigvir^® and five echovirus 7 isolates, and those sequences are further analyzed in this paper. A phylogenetic analysis of the full-length data suggested that Rigvir^® was most distant from the other E7 isolates used in this study, placing Rigvir^® in its own clade at the root of the phylogeny. Rigvir^® contained nine unique mutations in the viral capsid proteins VP1-VP4 across the whole data set, with a structural analysis showing six of the mutations concerning residues with surface exposure on the cytoplasmic side of the viral capsid. One of these mutations, E/Q/N162G, was located in the region that forms the contact interface between decay-accelerating factor (DAF) and E7. Rigvir^® and five other isolates were also subjected to cell infectivity assays performed on eight different cell lines. The used cell lines contained both cancer and non-cancer cell lines for observing Rigvir^®’s claimed properties of being both oncolytic and oncotropic. Infectivity assays showed that Rigvir^® had no discernable difference in the viruses’ oncolytic effect when compared to the Wallace prototype or the four other E7 isolates. Rigvir^® was also seen infecting non-cancer cell lines, bringing its claimed effect of being oncotropic into question. Thus, we conclude that Rigvir^®’s claim of being an effective treatment against multiple different cancers is not warranted under the evidence presented here. Bioinformatic analyses do not reveal a clear mechanism that could elucidate Rigvir^®’s function at a molecular level, and cell infectivity tests do not show a discernable difference in either the oncolytic or oncotropic effect between Rigvir^® and other clinical E7 isolates used in the study.