Different kinetics of lung clearance of technetium-99m labelled diethylene triamine penta-acetic acid in patients with sarcoidosis and smokers

The rate of clearance from the lungs of inhaled technetium-99m labelled diethylene triamine penta-acetic acid (^99mTc-DTPA) is often increased in interstitial lung disease as well as in smoking. In smokers a bi-exponential clearance course of ⁹⁹mTc-DTPA when measured over 3 h has previously been shown. This study was performed to compare the kinetics of clearance of ^99mTc-DTPA, measured for 3 h, in sarcoid patients and healthy smokers. Forty-one never-smoking patients with sarcoidosis and radiological signs of intrathoracic disease were studied. The results were compared with those of 16 healthy current smokers and of 14 healthy never-smokers reported previously. A mono-exponential clearance equation described the clearance in 22 of the sarcoid patients and all normal never-smokers, but with a shorter average tracer half-life in the patients (P<0.05). In 19 patients and all smokers a bi-exponential equation gave a significantly better curve fit. The rate of clearance of the slow component was higher in patients with sarcoidosis than in smokers (P< 0.05). The fraction of the tracer cleared by the fast clearance component was smaller in patients with sarcoidosis than in smokers (P<0.01). Differences in kinetics of clearance of ^99mTc-DTPA in sarcoidosis and smoking could thus be demonstrated, suggesting that the abnormal clearance is caused by diverging pathophysiological mechanisms.     

Development of a dietary screening questionnaire to predict excessive weight gain in pregnancy

Excessive gestational weight gain (GWG) is a risk factor for several adverse pregnancy outcomes, including macrosomia. Diet is one of the few modifiable risk factors identified. However, most dietary assessment methods are impractical for use in maternal care. This study evaluated whether a short dietary screening questionnaire could be used as a predictor of excessive GWG in a cohort of Icelandic women. The dietary data were collected in gestational weeks 11–14, using a 40‐item food frequency screening questionnaire. The dietary data were transformed into 13 predefined dietary risk factors for an inadequate diet. Stepwise backward elimination was used to identify a reduced set of factors that best predicted excessive GWG. This set of variables was then used to calculate a combined dietary risk score (range 0–5). Information regarding outcomes, GWG (n = 1,326) and birth weight (n = 1,651), was extracted from maternal hospital records. In total, 36% had excessive GWG (Icelandic criteria), and 5% of infants were macrosomic (≥4,500 g). A high dietary risk score (characterized by a nonvaried diet, nonadequate frequency of consumption of fruits/vegetables, dairy, and whole grain intake, and excessive intake of sugar/artificially sweetened beverages and dairy) was associated with a higher risk of excessive GWG. Women with a high (≥4) versus low (≤2) risk score had higher risk of excessive GWG (relative risk = 1.23, 95% confidence interval, CI [1.002, 1.50]) and higher odds of delivering a macrosomic offspring (odds ratio = 2.20, 95% CI [1.14, 4.25]). The results indicate that asking simple questions about women's dietary intake early in pregnancy could identify women who should be prioritized for further dietary counselling and support.     

Effect of increasing the dietary (n-3) to (n-6) polyunsaturated fatty acid ratio on murine liver and peritoneal cell fatty acids and eicosanoid formation

An incremental increase in the dietary (n-3):(n-6) polyunsaturated fatty acid (PUFA) ratio from 0 to 1.93 in diets containing 15% fat (wt/wt) decreased the total (n-6) PUFA content of phospholipids of the liver and peritoneal cells (macrophage) in mice from 43.1 and 33.6 mol/100 mol to 16.0 and 12.3 mol/100 mol with a concomitant increase of 27.6 and 16.1 mol/100 mol in (n-3) PUFA, respectively. Consumption of (n-3) PUFA increased hepatic (n-3) PUFA levels without changing total PUFA (46.35 vs. 46.87 mol/100 mol), whereas macrophage PUFA levels were decreased. The synthesis of sulfidopeptide leukotrienes (SP-LT) (LTC4 and LTE4) was progressively reduced by increasing dietary (n-3) PUFA, i.e., there was a reduction of 76% in mice fed a diet containing a (n-3):(n-6) PUFA ratio of 1.93 compared with the control diet. The 5-series SP-LT (LTC5 and LTF5) were produced in all animals consuming (n-3) PUFA and accounted for 62% of all SP-LT synthesized in mice fed the diet containing a 1.93 (n-3):(n-6) PUFA ratio. Synthesis of 6-keto-prostaglandin F1 alpha decreased 81% in mice fed a diet containing a (n-3):(n-6) PUFA ratio of 1.93 whereas prostaglandin E2 synthesis decreased 44% in mice fed diets with (n-3):(n-6) ratios ranging from 0.41 to 1.93.     

History of violence and subjective health of mother and child

Objective: To study the self-reported prevalence of experienced violence among a cohort of women about two years after giving birth, their health during pregnancy, pregnancy outcomes and their experience of their child’s health.

Setting and subjects: In 2011, a total of 657 women participated in phase III of the Childbirth and Health Cohort Study in Icelandic Primary Health Care, 18 to 24 months after delivery. The women had previously participated in phase I around pregnancy week 16 and phase II 5–6 months after delivery. Data were collected by postal questionnaires.

Main outcome measures: Women’s reported history of experienced violence, sociodemographic and obstetric background, self-perceived health, the use of medications and their child’s perceived health.

Results: In phase III, 16% of women reported experiencing violence. These women felt less support from their current partner (p?p?p?p?p?p?=?0.008).

Conclusions: Our study confirms that a history of violence is common among women. A history of violence is associated with various maternal health problems during and after pregnancy, a higher rate of caesarean sections and maternal reports of health problems in their child 18–24 months after birth.

• KEY POINTS

• Violence is a major concern worldwide. Understanding the impact of violence on human health and developing effective preventive measures are important elements of any public health agenda.

• ??The reported prevalence of experiencing violence was 16% among women attending antenatal care in the primary health care setting in Iceland.

• ??Women with a history of violence reported worse health in general during pregnancy and delivered more often by caesarean section, compared to women with no such history.

• ??Mothers with a history of violence also evaluated the general health of their child as worse than women with no such history.

• ??The findings of this study support the importance of recognizing and addressing experienced violence among women in primary care.

     

Genetic evidence for three unique components in primary cell-wall cellulose synthase complexes in Arabidopsis

In higher plants, cellulose is synthesized at the plasma membrane by the cellulose synthase (CESA) complex. The catalytic core of the complex is believed to be composed of three types of CESA subunits. Indirect evidence suggests that the complex associated with primary wall cellulose deposition consists of CESA1, -3, and -6 in Arabidopsis thaliana. However, phenotypes associated with mutations in two of these genes, CESA1 and -6, suggest unequal contribution by the different CESAs to overall enzymatic activity of the complex. We present evidence that the primary complex requires three unique types of components, CESA1-, CESA3-, and CESA6-related, for activity. Removal of any of these components results in gametophytic lethality due to pollen defects, demonstrating that primary-wall cellulose synthesis is necessary for pollen development. We also show that the CESA6-related CESAs are partially functionally redundant.     

CDKN2a mutation‐negative melanoma families have increased risk exclusively for skin cancers but not for other malignancies

Germline CDKN2A mutations are found in 5–20% of melanoma families. Numerous studies have shown that carriers of CDKN2A mutations have increased risks of non‐melanoma cancers, but so far there have been no studies investigating cancer risks in CDKN2A wild type (wt) melanoma families. In this prospective cohort study, index melanoma cases (n = 224) and their first‐degree relatives (n = 944) were identified from 154 confirmed CDKN2A wt melanoma families. Cancer diagnoses in family members and matched controls were obtained from the Swedish Cancer Registry. Relative risks (RR), odds ratios (OR) and two‐sided 95% confidence intervals (95% CI) were calculated. In index cases and first‐degree relatives, the prospective RR for melanoma was 56.9 (95% CI 31.4–102.1) and 7.0 (95% CI 4.2–11.4), respectively, and for squamous cell skin cancers 9.1 (95% CI 6.0–13.7) and 3.4 (95% CI 2.2–5.2), respectively. In neither group, elevated risks were seen for non‐skin cancers. In a subgroup analysis, CDKN2A wt melanoma families with young (<40 years) melanoma cases were found to have increased risk of non‐skin cancers (RR 1.5, 95% CI 1.0–1.5). Further, MC1R gene variants were increased in familial melanoma cases compared to controls (OR 2.4, 95% CI 1.6–3.4). Our findings suggest that in the majority of CDKN2A wt melanoma families, a segregation of variants in low‐risk melanoma genes such as MC1R causes increased skin cancer susceptibility, rather than mutations in high‐risk cancer predisposing genes, such mutations are more probable to be found in melanoma families with young melanoma cases. This study further supports an implication of CDKN2A mutation screening as a clinical test that determines counseling and follows up routines of melanoma families.     

Drug use during early pregnancy: Cross-sectional analysis from the Childbirth and Health Study in Primary Care in Iceland

Objective. To analyse drug use in early pregnancy with special focus on socio-demographic factors associated with psychotropic and analgesic drug use. Design. Cross-sectional study. Setting and subjects. A total of 1765 women were invited via their local health care centres, and 1111 participated at 11–16 weeks of pregnancy by filling out a postal questionnaire concerning socio-demographic and obstetric background, stressful life events, and drug use. Main outcome measures. Drug use prior to and early on in pregnancy, socio-demographic factors, smoking, and adverse life events were investigated. Drug categories screened for were psychotropics (collective term for antidepressants, relaxants, and sleep medication), analgesics, hormones, nicotine, vitamins/minerals, and homeopathic medicine. Results. Drug use from the aforementioned drug categories, excluding vitamins/minerals and homeopathic medicine, was reduced by 18% during early pregnancy, compared with six months prior to conception (49% vs. 60%). Psychotropic drug use during early pregnancy was associated with elementary maternal education (p < 0.5), being unemployed (p < 0.001), being single/divorced/separated (p < 0.01), smoking prior to or during pregnancy (p < 0.01), forced to change job/move house (p < 0.001), and psychotropic drug use six months prior to pregnancy (p < 0.001). No items on the stressful life events scale were associated with increased analgesic use, which increased only with multiparity. Conclusions. Use of analgesics and psychotropic drugs seems common in pregnancy. Our results indicate that lack of a support network, stressful life events, and lower status in society may predispose women to more drug use. GPs and midwives responsible for maternity care could take this into account when evaluating risk and gain for women and foetuses in the primary care setting.Key Words: Childbirth and health, drug use, general practice, Iceland, maternity care, pregnancy, primary health care, psychotropic drugsPregnant women are usually excluded from drug trials for ethical reasons.This study showed that:

• Almost half of the women were taking at least one drug during early pregnancy, excluding vitamins/minerals and homeopathic medicine.
• Significantly fewer women used drugs during early pregnancy, and those who did used drugs from fewer drug categories than compared with six months prior to pregnancy.
• Drug use during early pregnancy had the strongest correlation with drug use six months prior to pregnancy.
• Drug use during early pregnancy was associated with adverse life events and lower social position.

     

Smoking during pregnancy: Childbirth and Health Study in Primary Care in Iceland

Objective. To study the prevalence and possible predictors for smoking during pregnancy in Iceland. Design. A cross-sectional study. Setting. Twenty-six primary health care centres in Iceland 2009–2010. Subjects. Women attending antenatal care in the 11th–16th week of pregnancy were invited to participate by convenient consecutive manner, stratified according to residency. A total of 1111 women provided data in this first phase of the cohort study. Main outcome measures. Smoking habits before and during early pregnancy were assessed with a postal questionnaire, which also included questions about socio-demographic background, physical and emotional well-being, and use of medications. Results. The prevalence of smoking prior to pregnancy was 20% (223/1111). During early pregnancy, it was 5% (53/1111). In comparison with women who stopped smoking during early pregnancy, those who continued to smoke had on average a significantly lower level of education, had smoked more cigarettes per day before pregnancy, and were more likely to use nicotine replacement therapy in addition to smoking during pregnancy. A higher number of cigarettes consumed per day before pregnancy and a lower level of education were the strongest predictors for continued smoking during pregnancy. Conclusion. The majority of Icelandic women who smoke stop when they become pregnant, and the prevalence of smoking during pregnancy in Iceland is still about 5%. Our results indicate stronger nicotine dependence in women who do not stop smoking during pregnancy. Awareness of this can help general practitioners (GPs) and others providing antenatal care to approach these women with more insight and empathy, which might theoretically help them to quit.Key Words: Antenatal care, childbirth and health, general practice, Iceland, pregnancy, primary health care, smoking habitsSmoking during pregnancy is a major preventable risk factor for foetal and neonatal morbidity and mortality.

• This study shows that the prevalence of smoking during early pregnancy in Iceland is 5%.
• A history of heavy smoking before pregnancy and low level of education characterize the women who do not stop smoking early in pregnancy.
• Our results can help GPs and midwives to identify women at risk of continued smoking during pregnancy and possibly assist them to quit.

     

A study of the association between exercise‐induced wheeze and exercise versus methacholine‐induced bronchoconstriction in adolescents

Among asthmatics, exercise‐induced wheeze (EIW) is a frequent symptom, and 40–77% of asthmatics demonstrate exercise‐induced bronchoconstriction (EIB). In the North‐Trøndelag population‐based survey of 8,571 adolescents (YOUNG‐HUNT), 26% reported wheeze during the previous 12 months (current wheeze). Of those subjects, 50% reported EIW. The aim of the present study was to investigate the association between EIW and EIB in randomly selected adolescents with EIW as the only or predominant asthma‐like symptom, and to relate our findings to results from methacholine bronchoprovocation tests (MT) and measurements of exhaled nitric oxide (ENO). Sixty‐three subjects with current wheeze induced by exercise, but not by allergen exposure, were investigated using a treadmill exercise test (ET) and measurements of ENO. Fifty‐eight subjects completed a MT on a separate study day. EIB was defined as a fall of ≥ 10% in the forced expiratory volume in 1 second (FEV₁) after exercise (ΔFEV₁%_ex). Twenty‐one subjects (33%) had EIB and 33 (57%) had a positive MT. The degree of reported dyspnea during the ET was not correlated to the ΔFEV₁%_ex. The correlation between EIB and methacholine‐induced bronchoconstriction (MIB) was poor, and the ΔFEV₁%_ex was more pronounced in smokers than in non‐smokers. Moreover, ENO was not increased in subjects with positive vs. negative ET. Hence, EIW, when reported as the only or predominant asthma‐like symptom, was linked to EIB in only one‐third of the patients. We conclude that EIW is a poor predictor of EIB in epidemiological studies. The poor correlation between EIB and MIB indicates that these two tests measure different mechanisms of bronchial hyper‐responsiveness.