Subfertility among parents of men diagnosed with testicular cancer

It is well known that men with testicular cancer also have reduced fertility before diagnosis. It is unclear, however, whether their parents also have reduced fertility. We performed a population-based record linkage study comparing parental fertility among 3711 testicular cancer cases and 371 100 control males. The cases were diagnosed from 1961 to 2001, and the data were analysed by logistic regression. Included indicators of parental fertility were number of children, rate of unlike-sex twins as a proxy for dizygotic twinning rate, and proportion of boys. The number of children was reduced across increasing sibship size among both mothers [odds ratio (OR) = 0.95, p(trend) = 0.003] and fathers [OR = 0.97, p(trend) = 0.057] of subjects with testicular cancer. The proportion of unlike-sex twins was also reduced among their mothers [(OR = 0.56, p = 0.049 (adjusted for year of birth)] and fathers [(OR = 0.56, p = 0.049 (adjusted for year of birth)]. The results were only marginally changed when also adjusting for respective parental age. Our study indicates that parents of testicular cancer cases have reduced fertility. This suggests that genetic factors are important in the association between testicular cancer and reduced fertility.     

Parenthood after cancer - a population-based study

Many cancer forms today have good prognosis, and parenthood after cancer diagnosis and treatment has become a central research topic. Previous research has mainly focused on reproductive cancers, and few population-based studies exist.The effect of several cancer forms on fertility at a population level was explored. Discrete-time hazard regression models were used to analyse register and census data for complete Norwegian birth cohorts. Men and women 17-44 years in the period 1965-2001 were included. Models for first- and higher-order birth rates, for men and women, were estimated.Overall, first-birth rates among persons with cancer were reduced by only about 25% when compared with the general population. Male cancer survivors' second- and third-birth rates were similarly reduced, whereas higher-order birth rates for females were 36% below those of the general population. Significant decreases in cancer survivors' fertility disadvantage relative to the general population were seen from 1965 to 2001.Reductions in fertility were most pronounced for reproductive cancer forms, presumably related to subfecundity. However, also cancer forms unrelated to reproductive function led to reduced fertility, perhaps suggesting underlying social mechanisms. This is further supported by the difference in probability between first and subsequent births observed for women.     

Therapeutic hypothermia in neonates. Review of current clinical data, ILCOR recommendations and suggestions for implementation in neonatal intensive care units

Recent evidence suggests that the current ILCOR guidelines regarding hypothermia for the treatment of neonatal encephalopathy need urgent revision. In 2005 when the current ILCOR guidelines were finalised one large (CoolCap trial, n=235) and one small RCT (n=67), in addition to pilot trials, had been published, and demonstrated that therapeutic hypothermia after perinatal asphyxia was safe. The CoolCap trial showed a borderline overall effect on death and disability at 18 months of age, but significant improvement in a large subset of infants with less severe electroencephalographic changes. Based on this and other available evidence, the 2005 ILCOR guidelines supported post-resuscitation hypothermia in paediatric patients after cardiac arrest, but not after neonatal resuscitation. Subsequently, a whole body cooling trial supported by the NICHD reported a significant overall improvement in death or disability. Further large neonatal trials of hypothermia have stopped recruitment and their final results are likely to be published 2009-2011. Many important questions around the optimal therapeutic use of hypothermia remain to be answered. Nevertheless, independent meta-analyses of the published trials now indicate a consistent, robust beneficial effect of therapeutic hypothermia for moderate to severe neonatal encephalopathy, with a mean NNT between 6 and 8. Given that there is currently no other clinically proven treatment for infants with neonatal encephalopathy we propose that an interim advisory statement should be issued to support and guide the introduction of therapeutic hypothermia into routine clinical practice.     

Trace elements in cerebrospinal fluid and blood from patients with a rare progressive central and peripheral demyelinating disease

A hereditary neurological disease in a family in Norway has been reported recently. The disease, which we refer to as Skogholt's disease, is a demyelinating disorder of both the central and the peripheral nervous system with adult onset. We investigated whether changes in trace element concentrations could play a role in Skogholt's disease. Using high resolution inductively coupled plasma mass spectrometry, we determined 31 elements in cerebrospinal fluid (CSF), blood plasma and whole blood from these patients, multiple sclerosis patients and a control group. More than threefold increased levels of Cu and Fe, and a twofold increase in Zn were found in the CSF of Skogholt patients compared to controls. Several other significant differences in trace element levels were also found. The increased levels of Cu and Fe in CSF may indicate an active role of these metals in the pathogenesis of Skogholt's disease. Apparently, these metal ions are transferred into the CSF through their protein chelation, as raised protein levels were also seen. We suggest that redistribution of metals from transport proteins into vulnerable sites in the central (and peripheral) nervous system may initiate critical lesions.     

Swedish moist snuff accelerates gastric cancer development in Helicobacter pylori-infected wild-type and gastrin transgenic mice

The Swedish variant of moist oral smokeless tobacco (snus) is popular in Sweden and Norway, banned from sale within the European Union and is currently being introduced in USA. The aim of the present study was to determine if snus is carcinogenic to the stomach, particularly in Helicobacter pylori (H.P.)-infected hosts at increased risk for gastric cancer development. Snus (Generaltrade mark; Swedish Match, Sweden) was mixed with powdered standard mouse chow at a concentration of 5-9% (wt/wt) and given to wild-type (WT, FVB) and gastrin transgenic (INS-GAS, FVB) mice for 6 months with or without H.P. (strain 67:21, CagA+, VacA+) infection. At necropsy, pathological evaluation of stomachs from uninfected snus-treated WT mice showed mild morphological changes, whereas 50% snus-treated INS-GAS mice developed carcinoma in situ (CIS), compared with 25% not exposed to snus. When snus was given to H.P.-infected mice, 9 of 17 WT mice developed CIS with intramucosal invasion, and the remaining 8 of 17 WT mice developed high-grade dysplasia (score >1.5) that was associated with increased gastritis, epithelial defects, oxyntic atrophy, hyperplasia and intestinal metaplasia. Twelve of 12 H.P.-infected INS-GAS mice developed CIS with intramucosal invasion and submucosal herniation. We suggest that snus is a potential gastric carcinogen in mice. The development of CIS was associated with increased rates of the epithelial cell proliferation and apoptosis, common features of gastric carcinogenesis.     

Anxiety,depression, and heart disease in women

This is an extension of previous research that has reported on psychosocial risk factors in women participants in the Recurrent Coronary Prevention Project (RCPP). The RCPP women (N = 83) were under 65 years of age, non-diabetic, non-smoking and had experienced a myocardial infarction (MI) at least 6 months prior to the study. Baseline data was available on 80 RCPP subjects. Seventy three non-smoking, coronary disease-free women participants in the Stanford-Sunnyvale Health Improvement Project (SSHIP) served as a control-comparison group. Women with coronary heart disease had higher serum cholesterol than controls. There were no case-control differences in marital status, occupation, or number of children. RCPP women had Videotaped Structured Interview (VSI) Type A scores comparable to those of the SSHIP women, but had significantly higher VSI-hostility scores (p < .01). In addition. the post-MI women were rated more anxious and depressed, and had more avoidance symptoms than controls ( p < .01). Additional analyses involved the 65 RCPP women located at 8.5-year follow-up. In these women, univariate predictors of coronary recurrence (N = 13) were body mass index (kg/m)2. Peel Index, low time urgency (VSI) and high anxiety ( p < .05). Employment status, marital status, and education were not associated with subsequent cardiac events. These exploratory analyses suggest that the relations between heart disease and hostility, anxiety, and depression in women deserve further investigation.     

Bone marrow micrometastases in advanced stage non-small cell lung carcinoma patients

BACKGROUND: The clinical relevance of bone marrow micrometastases in non-small cell lung cancer (NSCLC) is undetermined, and the value of such analyses in advanced stage patients has not been assessed previously. METHODS: Immunomagnetic selection with the MOC31 (anti-EpCam) antibody was performed to isolate and detect tumor cells in bone marrow aspirates obtained from 196 patients with NSCLC, and the patients were subjected to follow-up for the assessment of survival. Repeated bone marrow samples, 2-7 samples per patient, were obtained from 13 long-term survivors. RESULTS: MOC31 positive tumor cells were detected in 107 of 196 (55%) samples, a frequency similar to results reported in low-stage patients prior to curative surgical resection for NSCLC. No association was found between the presence of bone marrow micrometastases and disease stage or histological subgroup, and survival was similar in patients with and without detectable tumor cells in bone marrow. Repeated bone marrow analysis revealed, for the first time in this group of patients, the continued presence of tumor cells regardless of the given therapy and treatment response. CONCLUSION: The immunomagnetic method utilized is a feasible strategy for the detection of bone marrow micrometastases in NSCLC. In advanced stage patients, the presence of MOC31 positive cells in bone marrow does not predict survival. Repeated analyses of bone marrow samples from long-term survivors revealed tumor cells in bone marrow which may represent dormant cells of particular interest for further characterization and follow-up.     

Positive affect as a factor of resilience in the pain-negative affect relationship in patients with rheumatoid arthritis

OBJECTIVE: The purpose of this study is to examine positive affect (PA) as a factor of resilience in the relationships between pain and negative affect (NA) in a sample of patients with rheumatoid arthritis. METHODS: Forty-three patients (30 women; mean age, 57 years) were interviewed weekly by telephone for 8 weeks. Multilevel modeling was applied to study the within-week relationships among the variables. RESULTS: There was a Pain x PA interaction effect on NA (beta=-0.05, P<.01) indicating a weaker relationship between pain and NA in weeks with more PA. Pain (beta=0.37, P<.002), interpersonal stress (beta=2.42, P<.001), depression (beta=0.26, P<.01), average perceived stress (beta=10.80, P<.001), and also weekly PA (beta=-0.1, P<.01) had a main effect upon NA. CONCLUSION: Positive affect is most influential in reducing NA during weeks of higher pain and may be a factor of resilience, helping patients experiencing pain fluctuations as less distressful than at lower levels of PA.     

Reduced inflammatory response by transcatheter,as compared to surgical aortic valve replacement

Objectives. The inflammatory response to on-pump cardiac surgery is well known. Systemic inflammatory response syndrome after transcatheter valve implantation (TAVI) has been reported. The objective of this study was to study the inflammatory response during TAVI, and compare with the response during surgical aortic valve replacement. Methods. Eighteen patients undergoing transcatheter implantation, either by a transfemoral (n?=?9) or transaortal (n?=?9) approach were compared with eighteen patients admitted for surgical replacement. Blood samples per- and postoperatively were analysed for C3bc, terminal complement complex, myeloperoxidase, macrophage inflammatory protein-1β, monocyte chemo-attractant peptide-1, eotaxin, IL-6 and troponin-T. All markers were measured at defined time points and the areas under the curve were compared. Results. Activation of complement, granulocytes, monocytes and eosinophils were significantly lower in the transcatheter group as compared to the surgical group (<0.01). There was no difference in generation of troponin T and IL-6. A small difference in complement activation was observed between the transfemoral and transaortal placement of TAVI. There was no significant difference in clinical outcomes between the TAVI and surgical groups. Discussion. Activation and release of inflammatory markers was significantly less during with TAVI as compared to SAVR, particularly for markers associated with extracorporeal circulation. TAVI and SAVR generated the same degree of IL-6 and troponin T, indicating that the burden on the myocardial tissue was the same.

Clinical Trials: Gov ID: NCT03074838 Unique protocol ID: 2012/7919