Two screening instruments for collecting alcohol-related information from expectant mothers and fathers: Testing the reliability of the Parent Alcohol Screening Questionnaire and the Social Support for an Alcohol-Free Pregnancy Questionnaire

The aim is to test the reliability of two alcohol screening instruments: (1) The Parent Alcohol Screening Questionnaire (PASQ5), and (2) the Social Support for an Alcohol-free Pregnancy (SSAFP) questionnaire. This is a cohort study from the south of Sweden using repeated surveys during pregnancy. To examine if responses differed according to different data collection methods, two cohorts consisting of 289 expectant mothers and 141 fathers completed the PASQ5 both verbally (weeks 6–7) and in writing (week 12) within regular antenatal visits. One of the cohorts (n = 137/64) also completed the SSAFP in week 12 and later in week 33. The third cohort, consisting of 179 and 133 expectant mothers and fathers, respectively, completed the PASQ5 and the SSAFP twice in late pregnancy (week 31 + 33). Eight of 10 items in the PASQ5 were stable for both expectant mothers and expectant fathers when comparing verbal versus written-delivered formats. Eight of 10 questions in the PASQ5 were stable when assessing the items in a test–retest analysis in late pregnancy for expectant mothers and nine of 10 questions were stable for fathers. The SSAFP items showed high internal consistency (0.86) for expectant mothers and excellent internal consistency (0.94) for expectant fathers. Most SSAFP items (17 of 21 for expectant mothers and 18 of 22 for expectant fathers) were also stable in a test–retest scenario in late pregnancy. Both the PASQ5 and SSAFP are reliable tools and may be helpful for clinicians who aim to have a deeper dialogue about alcohol consumption during pregnancy. These tools may also be helpful for researchers aiming to better understand a person's changes in alcohol intake and/or their social support network.     

Nerve-induced release of nitric oxide in the rabbit gastrointestinal tract as measured by in vivo microdialysis

1. Nitric oxide (NO) has been suggested as a gastrointestinal neurotransmitter, mediating the gastric receptive relaxation and the relaxation in the peristaltic reflex. The aim of the present study was to measure nerve-induced NO formation in vivo in the gastrointestinal tract.
2. Formation of the nitric oxide oxidation products nitrite and nitrate during vagal nerve stimulation were measured in the anaesthetized rabbit. Microdialysis probes were inserted into the wall of the stomach and proximal colon, and nitrite and nitrate in dialysate measured by capillary electrophoresis.
3. During bilateral vagal nerve stimulation there was an increase in nitrite and nitrate formation at the level of the stomach and in nitrite formation at the level of the colon. This increase was inhibited by intravenous administration of the NO synthase inhibitor N^ω-nitro-L-arginine methyl ester (L-NAME 30 mg kg⁻¹). Furthermore, L-NAME significantly increased nerve-induced gastric and colonic contractions, as well as spontaneous colonic contractions.
4. In summary, we present a new methodological procedure for quantification of small changes in nitric oxide formation in vivo. This study provides evidence that nitric oxide is released in the stomach and colonic wall during vagal nerve activity, at concentrations able to cause inhibition of smooth muscle contractions in vivo.

     

Influence of perinatal factors on the onset of puberty in boys and girls: implications for interpretation of link with risk of long term diseases.

The authors examined the hypothesis that perinatal factors influence the onset of puberty. Children born as singletons in Uppsala, Sweden, in 1973-1977 were followed for height development before and during their school years (through 16 years of age). In all, 62 children born after preeclampsia, 129 born prematurely, 90 born small for gestational age, 175 born large for gestational age, 49 born short for gestational age, and 38 born tall for gestational age were compared with 688 "normal" children. Differences in age and height at puberty onset and age at menarche were analyzed using the t test and analyses of covariance. For boys, the mean age at puberty onset did not differ between normal boys and those with perinatal factors. Boys born small or short for gestational age were 4 cm shorter than normal boys, and those born large for gestational age were 3 cm taller than normal boys. Among girls, patterns for differences in height were similar. Girls born small for gestational age were 5 months younger than normal girls at the onset of puberty and menarche. Patterns of early childhood growth seemed to explain the relations between these perinatal factors and height and age at puberty. The authors conclude that body size at birth affects stature at puberty; in girls, smallness for gestational age is associated with earlier puberty. Associations between intrauterine exposures and disease risk may be confounded by, or mediated through, effects on adolescence.     

Release of intracellular enzymes from cutaneous cells after non-necrotizing damage by ultraviolet light

Summary Experimental blisters were produced with suction on normal human skin and simultaneously on skin inflamed after exposure to middle wave ultraviolet light. Total proteins and marker enzymes for the plasma membrane, cytosol, lysosomes, peroxisomes, mitochondria, and microsomes were assayed in the blister fluid. In blisters on erythematous skin, a large increase of lactate dehydrogenase from cytosol was noted. A small increase of the plasma membrane marker phosphodiesterase I and some increase of -mannosidase from lysosomes was also found. No significant increase in total proteins or in the markers for peroxisomes was observed, whereas mitochondrial and microsomal marker enzymes were not detectable.It is concluded that cutaneous cells to some extent may lose intracellular enzymes without visible signs of irreversible damage (necrosis), but that an UVB-induced injury/regeneration cycle probably explains the enzyme release.     

Genetic analysis of the RNASEL gene in hereditary, familial, and sporadic prostate cancer.

PURPOSE: The RNASEL gene has been proposed as a candidate gene for the HPC1 locus through a positional cloning and candidate gene approach. Cosegregation between the truncating mutation E265X and disease in a hereditary prostate cancer (HPC) family and association between prostate cancer risk and the common missense variant R462Q has been reported. To additionally evaluate the possible role of RNASEL in susceptibility to prostate cancer risk, we performed a comprehensive genetic analysis of sequence variants in RNASEL in the Swedish population. EXPERIMENTAL DESIGN: Using 1624 prostate cancer cases and 801 unaffected controls, the truncating mutation E265X and five common sequence variants, including the two missense mutations R462Q and D541E, were evaluated for association between genotypes/haplotypes and prostate cancer risk. RESULTS: The prevalence of E265X carriers among unaffected controls and prostate cancer patients was almost identical (1.9 and 1.8% in controls and cases, respectively), and evidence for segregation of E265X with disease was not observed within any HPC family. Overall, the analyses of common sequence variants provided limited evidence for association with prostate cancer risk. We found a marginally significant inverse association between the missense mutation D541E and sporadic prostate cancer risk (odds ratio, 0.77; 95% confidence interval, 0.59-1.00) and reduced risk of prostate cancer in carriers of two different haplotypes being completely discordant. CONCLUSIONS: Considering the high quality in genotyping and the size of this study, these results provide solid evidence against a major role of RNASEL in prostate cancer etiology in Sweden.     

Nucleated red blood cells in cord blood of singleton term neonates

OBJECTIVE: This study aims to establish normal values for nucleated red blood cells in term singletons and factors associated with their elevation.STUDY DESIGN: Cord blood was prospectively collected from term singleton gestations from Feb. 1 to July 31, 1995. Umbilical vein white blood cells and nucleated red blood cells were counted and umbilical arterial pH was determined. Medical records provided maternal and neonatal information.RESULTS: Cord blood from 1112 cases was obtained and evaluated for nucleated red blood cells per 100 white blood cells. Nine outliers were censored (nucleated red blood cells per 100 white blood cells = 126 to 830); five cases were excluded because of missing data. The mean value of nucleated red blood cells per 100 white blood cells was 8.55, the SD was 10.27, and the range was 0 to 89. The value did not vary by maternal tobacco or drug use, anemia, fetal presentation, or mode of delivery. Both maternal diabetes and meconium were associated with elevated values, p < 0.01. Apgar scores and cord pHs showed trends toward inverse proportionality to the number of nucleated red blood cells per 100 white blood cells.CONCLUSION: The mean number of nucleated red blood cells per 100 white blood cells was 8.55, with a wide range and SD. Elevated values may be associated with markers of intrauterine hypoxia such as meconium, lower Apgar scores, and lower pH values. (Am J Obstet Gynecol 1997;176:1149-56.)     

Cytogenetics of benign breast lesions

This review summarizes the cytogenetic information on benign breast lesions of various histologies, i.e., fibrocystic lesions from women with and without a known hereditary predisposition to breast cancer, fibroadenomas, phyllodes tumors, and papillomas, and relate the chromosomal features with those in breast carcinoma. In general, the frequency of chromosome abnormalities is lower in benign lesions than in breast cancer, and seems to correlate with the histologic features of the tissue, and the corresponding risk of developing invasive mammary carcinoma; aberrations are more common in proliferative than in nonproliferative lesions. The karyotypes are generally less complex than those detected in invasive carcinoma, and more often involve balanced rearrangements. No lesion-specific aberration has so far been detected; on the contrary, changes repeatedly encountered in breast cancer samples can be found in benign lesions as well, e.g., gain of 1q, interstitial deletion of 3p, and trisomies 7, 18, and 20. Especially intriguing is the prevalence of rearrangements of the short arm of chromosome 3, with the minimally deleted bands 3p13–14, in proliferative lesions from prophylactic mastectomies in breast cancer families. The potential tumor suppressor gene(s) in this region remains, however, to be identified.     

A European validation study of smoking and environmental tobacco smoke exposure in nonsmoking lung cancer cases and controls

Objectives: The purpose of this study was to validate, in a case-control study, the reporting by lung cancer cases and controls of their own lifetime smoking habits and of the smoking habit of the spouse. Methods: In a multicenter (Sweden, Spain, Italy) case-control study of environmental tobacco smoke (ETS) and lung cancer, subjects were screened by repeated probing to exclude regular smokers of one cigarette/day or more for one year or more, and to quantify any occasional smoking. We then performed a short validation interview with next-of-kin in three centers. Results: Only five of 408 index subjects who had never smoked regularly (1.7 percent) were reported by next-of-kin to be former regular smokers. These subjects had a cumulative lifetime consumption of cigarettes below 1.1 pack years. Among 351 subjects with quantitative smoking information from both sources who reported ever smoking 400 cigarettes or less (the definition of never-smoker used in the multicenter ETS study), nine subjects (2.6 percent) had smoked more than this amount occasionally according to next-of-kin. Misclassification was not higher for cases than controls. Relative risks for lung cancer associated with indicators of ETS exposure were not substantially altered by excluding the nine possibly misclassified subjects. The reports from 223 pairs of index subjects and next-of kin regarding the cumulative amount smoked by the spouse agreed quite well (Spearman's rank correlation 0.75 for reported smokers, 0.92 for all subjects). Only one index subject failed to report a spouse who had smoked regularly (99 percent sensitivity). Conclusions: Smoking status and exposure to spousal ETS as reported by lung cancer cases and controls agreed strongly with reports by next-of-kin. Overall, our results suggest that bias from smoker misclassification is likely to be insignificant, and they contribute to the evidence linking exposure to ETS with an increased risk of lung cancer.     

Addition of histamine to interleukin 2 treatment augments type 1 T-cell responses in patients with melanoma in vivo: immunologic results from a randomized clinical trial of interleukin 2 with or without histamine (MP 104).

PURPOSE: Preclinical investigations suggest that histamine dihydrochloride (HDC) protects T cells and natural killer cells from inhibition by monocyte-derived reactive oxygen metabolites and synergizes with interleukin (IL) 2 in inducing T-cell activation. Here, we investigate whether this mechanism is operational in patients with melanoma treated with HDC as an adjunct to IL-2. EXPERIMENTAL DESIGN: Melanoma patients having liver metastases were treated with IL-2 with or without HDC within a randomized, multicenter, phase III trial. The effect of HDC on type 1 and type 2 T-cell cytokine production was investigated in peripheral blood samples from 19 patients with the use of intracellular cytokine flow cytometry. Melanoma-specific T-cell responses were analyzed in eight HLA-A2-positive patients. RESULTS: Frequencies of CD3+ T cells producing IFN-gamma (type 1 T cells) in response to phorbol myristate acetate/ionomycin increased (median, 1.8-fold) in patients receiving IL-2 plus HDC but not in those receiving IL-2 alone (P < 0.01 for comparison between arms). In contrast, the number of IL-13-producing type 2 T cells that increased in patients after treatment with IL-2 was not modulated by HDC. Melanoma- and tyrosinase-specific IFN-gamma and IL-13-producing T cells were detected in two of four HLA-A2-positive patients with melanoma following treatment with HDC + IL-2. CONCLUSIONS: Treatment of patients with stage IV melanoma with HDC in combination with IL-2 increases type 1 T-cell responses and may promote induction of melanoma-specific T cells. These effects are of relevance for tumor immunotherapy and provide a potential mechanism for the clinical efficacy of HDC added to IL-2.     

Risk of suicide in men with low-risk prostate cancer

PurposeRisk of suicide is increased among men with prostate cancer. We investigated this association among men with low-risk cancer, usually detected by prostate specific antigen (PSA)-testing.Patients and MethodsRelative risk (RR) of suicide was calculated by use of Poisson regression analysis within the Prostate Cancer data Base Sweden (PCBaSe) 2.0, a nation-wide, population-based database, comparing 105,736 men diagnosed with prostate cancer between 1997–2009 to 528,658 matched prostate cancer-free men.ResultsDuring the first 6 months after diagnosis, there were 38 suicides among men with prostate cancer; incidence rate 0.73 per 1000 person-years (PY) and 30 suicides in the comparison cohort; 0.11 per 1000 PY, corresponding to a RR of suicide of 6.5 (95% confidence interval (CI) 4.0–10). Risk was highest among men with distant metastases, incidence rate 1.25 per 1000 PY, RR 10 (95% CI 5.1–21) but risk was also increased for men with low-risk tumours, incidence rate difference 0.45 per 1000 PY and RR 5.2 (95% CI 2.3–12) and across categories of socioeconomic status and comorbidity. Eighteen months after diagnosis, risk of suicide had decreased to 0.27 per 1000 PY, RR 1.0 (95% CI 0.68–1.5) for low-risk prostate cancer but remained increased among men with metastases, 0.57 per 1000 PY, RR 1.8 (95% CI 1.1–2.9).ConclusionAlthough the increase in absolute risk of suicide was modest, our findings reflect the severe psychological stress that prostate cancer patients may experience after diagnosis. The increased risk of suicide observed in men with prostate cancer, including low-risk, calls for increased awareness.