Thermogenic effect of bronchodilators in patients with chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are frequently malnourished and have increased resting energy expenditure (REE). An increase in the work of breathing is generally considered to be the main cause of this hypermetabolism, but other factors may also be implicated. Bronchodilators may decrease the work of breathing by reducing airway obstruction, but beta 2 adrenergic agents have a thermogenic effect. The aim of this study was to determine the effect of salbutamol and ipratropium bromide administration on REE in patients with COPD. METHODS: Thirteen patients (10 men) of mean (SD) age 68.3 (7.3) years and forced expiratory volume in one second (FEV1) 39.0 (17.0)% predicted were studied on three consecutive days. The REE was measured by indirect calorimetry at 30, 60, 120, and 180 minutes after double blind nebulisation of either salbutamol, ipratropium bromide, or placebo in random order. RESULTS: FEV1 increased both after salbutamol and after ipratropium. The difference in the mean response between salbutamol and placebo over 180 minutes was +199 ml (95% CI +104 to +295). The difference in mean response between ipratropium and placebo was +78 ml (95% CI +2 to +160). REE increased after salbutamol but was not changed after ipratropium. The difference in mean response between salbutamol and placebo was +4.8% of baseline REE (95% CI +2.2 to +7.4). Heart rate increased after salbutamol but not after ipratropium. The difference in the mean response between salbutamol and placebo was +5.5 beats/ min (95% CI +2.6 to +8.4). CONCLUSION: Salbutamol, but not ipratropium bromide, induces a sustained increase in the REE of patients with COPD despite a reduction in airway obstruction.

Recurrent idiopathic neuroretinitis: natural history and effect of treatment.

BACKGROUND: Previous reports have emphasized the self-limited nature of idiopathic neuroretinitis. There is less information about a subgroup of patients who suffer recurrent episodes with worse visual outcome. We sought to better characterize the clinical features of recurrent idiopathic neuroretinitis including the effects of immunosuppressive treatment. METHODS: Retrospective chart review of neuroretinitis patients from a single institution from 1983 to 2008. Inclusion criteria included two or more episodes of acute visual loss with disc oedema and macular exudates in a star pattern. Cases due to a specific infectious or inflammatory aetiology were excluded. RESULTS: Forty-one patients were included with an average follow up of 67 months. Median age at the time of the first episode was 28 years (range 10-54 years). Attacks were bilateral sequential in 34 patients (83%). We documented a total of 147 episodes in 75 eyes with an average of 3.6 attacks per patient. The average interval between attacks was 3 years. Visual field loss had a nerve fibre bundle pattern in most cases. Only 36% of eyes retained 6/12 or better visual acuity and greater than two-thirds of their visual field. Long-term immunosuppressive treatment in 13 patients decreased the attack rate by 72%. CONCLUSIONS: Recurrent idiopathic neuroretinitis typically affects young adults, with no gender preference. Recovery is limited and visual loss is cumulative with repeated attacks, often resulting in severe permanent visual loss. Immunosuppressive treatment appears to lessen the attack frequency.

Deteriorated visual backward masking in the shine-through effect in adolescents with psychosis.

Visual backward masking is a reliable and widely used tool in schizophrenia research. Whereas many studies have shown masking deficits in adult patients, there are only very few studies with adolescents with psychosis-and with controversial results. Masking deficits of adolescents are of primary interest because they are not caused by long-term suffering from the disease and severe medication. We investigated 15 adolescents with psychosis and 19 age-matched controls in the shine-through backward masking paradigm for which strong performance deficits were shown previously in adult schizophrenic patients and their relatives. Adolescents with psychosis were strongly impaired in the shine-through effect compared to controls. This result adds further evidence that backward masking is an endophenotype of schizophrenia.

Effect of vaccination against gonadotrophin-releasing hormone, using Improvac®, on growth performance, body composition, behaviour and acute phase proteins

The objective of this study was to evaluate the effect of vaccination against GnRH on performance traits, pig behaviour and acute phase proteins. A total of 120 pigs (36 non-castrated males, NCM; 36 males to be vaccinated, IM; 24 castratedmales, CM; and 24 females, FE)were controlled in groups of 12 in pens with feeding stations allowing the recording of individual feed intake. The two vaccinations (Improvac®) were applied at a mean age of 77 and 146 days. All pigswere individually weighed every 3 weeks from the mean ages of 74 to 176 days and backfat thickness (BT) and loinmuscle depth (LD) were also recorded ultrasonically. Twelve group-housed pigs for each treatment were video recorded during 2 consecutive days at weeks 9, 11, 20, 21, 23 and 25 of age to score the number of inactive or active pigs in each treatment group by scan sampling. Aggressive behaviour by the feeder and away from the feeder, and mounting behaviour was also scored by focal sampling. Blood samples from 12 NCM, 12 CM and 12 IM were taken to determine the concentration of circulating acute phase protein Pig-MAP atweeks 1, 2, 4, 11, 13, 21 and 25 of age. After slaughter, the number of skin lesions on the left half carcasswas scored. IMpresented overall a higher growth rate and daily feed intake compared to NCM (Pb0.05),whereas their feed conversion ratios did not differ significantly. In comparison with CM, IM presented a better feed conversion ratio (Pb0.05), since their overall dailyweight gaindid not differ significantly, butIM ate less. Final leanmeat percentage of IM and CM was lower compared to that of NCM (Pb0.05). Activity, mounting and aggressive behaviour of NCM was higher than in IM, CM and FE after the second vaccination. Pig-MAP concentrationswere significantly elevated just after surgical castrationand after bothadministrations of the vaccine (Pb0.05), but concentrations subsequently decreased throughout time. Skin lesions of NCM were significantly higher compared to that of IM and FE (Pb0.05). The effects of vaccination were especially remarkable after the second dose, when the higher feed intake and lower activity of IM compared to NCMmight result in higher final body weight and more fat. Results from this study indicate that some welfare aspects such as a reduced aggression and mounting behaviour may be improved by vaccination against GnRH, together with productive benefits like adequate feed conversion ratio and daily weight gain.

Effect of Sodium Loading/Depletion on Renal Oxygenation in Young Normo-and Hypertensive Men Measured with BOLD-MRI

Objective: To measure renal tissue oxygenation in young normo-and hypertensive volunteers under conditions of salt loading and depletion using blood oxygen level dependent magnetic resonance imaging (BOLD-MRI). Design and Methods: Ten normotensive (NT) male volunteers (age 26.5_7.4 y) and eight non-treated, hypertensive (HT) male volunteers (age 28.8_5.7 y) were studied after one week on a high salt (HS) regimen (6g of salt/day added to their normal regimen) and again after one week of a low sodium diet (LS). On the 8th day, BOLD-MRI was performed under standard hydration conditions. Four coronal slices were selected in each kidney, and combination sequence was used to acquire T2* weighted images. The mean R2* (1/T2*) was measured to determine cortical and medullar oxygenation. Results: Baseline characteristics and their changes are shown in the table. The mean cortical R2* was not different under conditions of HS or LS (17.8_1.3 vs. 18.2_0.6 respectively in NT group, p_0.27; 17.4_0.6 vs 17.8_0.9 in HT group, p_0.16). However, the mean medullary R2* was significantly lower under LS conditions in both groups (31.3_0.6 vs 28.1_0.8 in NT group, p_0.05; 30.3_0.8 vs 27.9_1.5 in HT group, p_0.05), corresponding to higher medullary oxygenation as compared to HS conditions, without significant changes in hemoglobin or hematocrit values. The salt induced changes in medullary oxygenation were comparable in the two groups (ANOVA, p_0.1). Conclusion: Dietary sodium restriction leads to increased renal medullary oxygenation compared to high sodium intake in normo-and hypertensive subjects. This observation may in part explain the potential renal benefits of a low sodium intake.

Age structure and abundance in populations of muscoid flies from a poultry facility in Southeast Brazil

Muscina stabulans, M. domestica, Chrysomya putoria, C. megacephala and Stomoxys calcitrans were the most abundant muscoid flies captured in a poultry facility in southeastern Brazil. We examined the gonadotrophic profiles of the females caught at different sites and different times and found that Mu. stabulans and M. domestica, the predominant species, presented similar gonadotrophic profiles only when captured on the manure under the cages, but very different and sometimes opposite gonadotrophic profiles when sampled from wooden posts, vegetation or electric cords. We also determined sex ratios and relative abundance for these two species and found significant differences between them. More than 50% of the females of both species of Chrysomya captured on manure carried eggs or exhibited signs of recent oviposition. The vast majority of S. calcitrans presented ovaries with eggs or signs of recent oviposition. A small proportion of them had ovaries in the recent emerged condition. Our data on ovarian stages, sex ratio and relative abundance allowed us to associate different gonadotrophic profiles with each site and characterize each site as a resting, ovipositing or mating site.

Effect of moderate hyperventilation and induced hypertension on cerebral tissue oxygenation after cardiac arrest and therapeutic hypothermia.

AIM: Improving cerebral perfusion is an essential component of post-resuscitation care after cardiac arrest (CA), however precise recommendations in this setting are limited. We aimed to examine the effect of moderate hyperventilation (HV) and induced hypertension (IH) on non-invasive cerebral tissue oxygenation (SctO2) in patients with coma after CA monitored with near-infrared spectroscopy (NIRS) during therapeutic hypothermia (TH). METHODS: Prospective pilot study including comatose patients successfully resuscitated from out-of-hospital CA treated with TH, monitored with NIRS. Dynamic changes of SctO2 upon HV and IH were analyzed during the stable TH maintenance phase. HV was induced by decreasing PaCO2 from ∼40 to ∼30 mmHg, at stable mean arterial blood pressure (MAP∼70 mmHg). IH was obtained by increasing MAP from ∼70 to ∼90 mmHg with noradrenaline. RESULTS: Ten patients (mean age 69 years; mean time to ROSC 19 min) were studied. Following HV, a significant reduction of SctO2 was observed (baseline 74.7±4.3% vs. 69.0±4.2% at the end of HV test, p<0.001, paired t-test). In contrast, IH was not associated with changes in SctO2 (baseline 73.6±3.5% vs. 74.1±3.8% at the end of IH test, p=0.24). CONCLUSIONS: Moderate hyperventilation was associated with a significant reduction in SctO2, while increasing MAP to supra-normal levels with vasopressors had no effect on cerebral tissue oxygenation. Our study suggests that maintenance of strictly normal PaCO2 levels and MAP targets of 70mmHg may provide optimal cerebral perfusion during TH in comatose CA patients.

Age-specific incidence of all neoplasms after colorectal cancer.

PURPOSE: Patients diagnosed with a specific neoplasm tend to have a subsequent excess risk of the same neoplasm. The age incidence of a second neoplasm at the same site is approximately constant with age, and consequently the relative risk is greater at younger age. It is unclear whether such a line of reasoning can be extended from a specific neoplasm to the incidence of all neoplasms in subjects diagnosed with a defined neoplasm. METHODS: We considered the age-specific incidence of all non-hormone-related epithelial neoplasms after a first primary colorectal cancer (n = 9542) in the Vaud Cancer Registry data set. RESULTS: In subjects with a previous colorectal cancer, the incidence rate of all other epithelial non-hormone-related cancers was stable around 800 per 100,000 between age 30 and 60 years, and rose only about twofold to reach 1685 at age 70 to 79 years and 1826 per 100,000 at age 80 years or older. After excluding synchronous cancers, the rise was only about 1.5-fold, that is, from about 700 to 1000. In the general population, the incidence rate of all epithelial non-hormone-related cancers was 29 per 100,000 at age 30 to 39 years, and rose 30-fold to 883 per 100,000 at age 70 to 79 years. Excluding colorectal cancers, the rise of all non-hormone-related cancers was from 360 per 100,000 at age 40 to 49 years to 940 at age 70 to 79 years after colorectal cancer, and from 90 to 636 per 100,000 in the general population (i.e., 2.6- vs. 7.1-fold). CONCLUSIONS: The rise of incidence with age of all epithelial non-hormone-related second cancers after colorectal cancer is much smaller than in the general population. This can possibly be related to the occurrence of a single mutational event in a population of susceptible individuals, although alternative models are plausible within the complexity of the process of carcinogenesis.

The effect of isolation on the life-history traits of Pseudosuccinea columella (Pulmonata: Lymnaeidae)

A population of Pseudosuccinea columella was raised under laboratory conditions and its life tables were determined in isolated and paired snails. Isolated snails were significantly larger in shell size than paired snails from five weeks of age onward. Also, statistically significant differences were found for the number of eggs per mass per individual from week 5 to 9, isolated snails exhibiting the highest values. The intrinsic and finite rates of increase were greater in isolated than in paired snails. Either an inhibition of the reproductive output between individuals or the advantage of selfing may be the cause of the differences in this species, acting as a possible mechanism that increase the fitness of isolated snails.

The effect of retirement on cognitive functioning

Cognitive impairment has emerged as a major driver of disability in old age, with profound effects on individual well-being and decision making at older ages. In the light of policies aimed at postponing retirement ages, an important question is whether continued labour supply helps to maintain high levels of cognition at older ages. We use data of older men from the US Health and Retirement Study to estimate the effect of continued labour market participation at older ages on later-life cognition. As retirement itself is likely to depend on cognitive functioning and may thus be endogenous, we use offers of early retirement windows as instruments for retirement in econometric models for later-life cognitive functioning. These offers of early retirement are legally required to be nondiscriminatory and thus, inter alia, unrelated to cognitive functioning. At the same time, these offers of early retirement options are significant predictors of retirement. Although the simple ordinary least squares estimates show a negative relationship between retirement duration and various measures of cognitive functioning, instrumental variable estimates suggest that these associations may not be causal effects. Specifically, we find no clear relationship between retirement duration and later-life cognition for white-collar workers and, if anything, a positive relationship for blue-collar workers. Copyright © 2011 John Wiley & Sons, Ltd.

CYP3A5 and ABCB1 genes influence blood pressure and response to treatment, and their effect is modified by salt.

The permeability-glycoprotein efflux-transporter encoded by the multidrug resistance 1 (ABCB1) gene and the cytochromes P450 3A4/5 encoded by the CYP3A4/5 genes are known to interact in the transport and metabolism of many drugs. Recent data have shown that the CYP3A5 genotypes influence blood pressure and that permeability-glycoprotein activity might influence the activity of the renin-angiotensin system. Hence, these 2 genes may contribute to blood pressure regulation in humans. We analyzed the association of variants of the ABCB1 and CYP3A5 genes with ambulatory blood pressure, plasma renin activity, plasma aldosterone, endogenous lithium clearance, and blood pressure response to treatment in 72 families (373 individuals; 55% women; mean age: 46 years) of East African descent. The ABCB1 and CYP3A5 genes interact with urinary sodium excretion in their effect on ambulatory blood pressure (daytime systolic: P=0.05; nighttime systolic and diastolic: P<0.01), suggesting a gene-gene-environment interaction. The combined action of these genes is also associated with postproximal tubular sodium reabsorption, plasma renin activity, plasma aldosterone, and with an altered blood pressure response to the angiotensin-converting enzyme inhibitor lisinopril (P<0.05). This is the first reported association of the ABCB1 gene with blood pressure in humans and demonstration that genes encoding for proteins metabolizing and transporting drugs and endogenous substrates contribute to blood pressure regulation.

Descriptive epidemiology of skin cancer in the Swiss Canton of Vaud.

Incidence registration and survival data for non-melanocytic skin neoplasms and cutaneous melanoma have been abstracted from the population-based system of the Cancer Registry of the Swiss Canton of Vaud, which has been operating in a particularly favourable environment, since the large majority of cutaneous lesions resected in the area are examined by a pathologist. Among the 5,712 cases registered, 66.7% were basal-cell carcinomas, 20.6% squamous-cell cancers, 9.3% cutaneous melanomas and 3.4% other miscellaneous histological types. The distribution by histological type did not differ appreciably in the 2 sexes, but there were marked inter-sex differences as regards anatomical site. In both sexes, head and neck was by far the commonest localization for non-melanomatous neoplasms (69 to 81% of all incident cases), followed by trunk for basal-cell cancers (18% in males, 15% in females) and upper limb for squamous-cell (10% in males, 17% in females). The distribution of skin melanomas differed considerably between the 2 sexes, by far the commonest site being the trunk for males (45% of cases) and lower limbs for females (40%), followed by head and neck (22% in both sexes). Incidence rates for both basal- and squamous-cell cancers increased with age, and rates were higher in males for each localization except the lower limb. In contrast, incidence for melanoma was higher in females, and incidence rates did not increase with age above 55 years for all sites except head and neck. This can be interpreted in terms of cohort effect, since mortality from melanoma has substantially increased in Switzerland across subsequent birth cohorts. Although this study is essentially descriptive, accurate inspection of these data provides some support for the major aetiological hypotheses of skin carcinogenesis, i.e., the observation that the large majority of basal- and squamous-cell cancers arise on the head and neck confirms the importance of long-term ultraviolet exposure; the relative excess of squamous-cell as compared to basal-cell neoplasms on the upper limb may suggest the role of exposure to other (chemical) carcinogens; and the proportional excess of melanomas on the trunk in males and lower limb in females further indicates that intermittent exposure to sunlight is probably the relevant aetiologic factor for melanocytic skin neoplasms.

Influence of quinidine on the pharmacokinetics of trimipramine and on its effect on the waking EEG of healthy volunteers. A pilot study on two subjects.

The pharmacokinetics and pharmacodynamics (waking EEG) of 75 mg trimipramine taken orally were determined in two healthy volunteers on two separate occasions, once without and once after comedication with 2 x 50 mg quinidine. Quinidine, a potent cytochrome P-450IID6 inhibitor, is used as a pharmacological tool to mimic a lack of this enzyme in man. In this study, it markedly altered the pharmacokinetics of trimipramine, almost doubling its plasma half-life and decreasing its apparent clearance and volume of distribution. These results strongly suggest that trimipramine is a substrate of cytochrome P-450IID6. These modifications of trimipramine metabolism were accompanied by measurable changes in some EEG variables, most notably with regard to the relative power in the alpha and theta bands, which showed higher and longer-lasting effects of trimipramine. Since cytochrome P-450IID6 is deficient in 5-10% of Caucasian subjects, this may have consequences in trimipramine-treated subjects, especially with regard to the effects of the drug on the EEG.

Effect of malaria and fever on energy metabolism in Gambian children.

The aim of the present study was to measure the changes in resting energy expenditure (REE) induced by malaria and to assess to what extent they are related to fever and nutritional status. The REE of 19 Gambian children (mean age +/- SEM, 9 +/- 1 y; weight, 24 +/- 2 kg; expected weight for height 86 +/- 1%) were measured with a hood system at repeated intervals at the onset of malaria crisis (test A), 3 to 4 d after therapy (test B), and 14 to 21 d later (test C). Axillary temperature averaged 39.2 +/- 0.1, 36.6 +/- 0.1, and 36.7 +/- 0.1 degrees C in the tests A, B, and C, respectively. REE in test A was significantly higher than REE in test B (223 +/- 10 versus 174 +/- 8 kJ/kg.d, p less than 0.0001), but in test C (169 +/- 8 kJ/kg.d), it did not differ from that observed in test B. The percentage of increase in REE was significantly correlated with the difference in axillary temperature (r = 0.46, p less than 0.05); the slope of the regression line indicated an increase of 6.9% in REE/degree C of fever. Furthermore, the individual increase in REE/degree C was correlated to the percentage of weight for height of the children (r = 0.54, p less than 0.05), indicating that the child's nutritional status influences the magnitude of the hypermetabolism due to fever. We concluded that Gambian children suffering from an acute episode of malaria have an increase in REE averaging 30%; however, REE promptly returns to baseline value a few days after the beginning of therapy.

Does lamotrigine use in pregnancy increase orofacial cleft risk relative to other malformations?

OBJECTIVE: To investigate whether first trimester exposure to lamotrigine (LTG) monotherapy is specifically associated with an increased risk of orofacial clefts (OCs) relative to other malformations, in response to a signal regarding increased OC risk. METHODS: Population-based case-control study with malformed controls based on EUROCAT congenital anomaly registers. The study population covered 3.9 million births from 19 registries 1995-2005. Registrations included congenital anomaly among livebirths, stillbirths, and terminations of pregnancy following prenatal diagnosis. Cases were 5,511 nonsyndromic OC registrations, of whom 4,571 were isolated, 1,969 were cleft palate (CP), and 1,532 were isolated CP. Controls were 80,052 nonchromosomal, non-OC registrations. We compared first trimester LTG and antiepileptic drug (AED) use vs nonepileptic non-AED use, for mono and polytherapy, adjusting for maternal age. An additional exploratory analysis compared the observed and expected distribution of malformation types associated with LTG use. RESULTS: There were 72 LTG exposed (40 mono- and 32 polytherapy) registrations. The ORs for LTG monotherapy vs no AED use were 0.67 (95% CI 0.10-2.34) for OC relative to other malformations, 0.80 (95% CI 0.11-2.85) for isolated OC, 0.79 (95% CI 0.03-4.35) for CP, and 1.01 (95% CI 0.03-5.57) for isolated CP. ORs for any AED use vs no AED use were 1.43 (95% CI 1.03-1.93) for OC, 1.21 (95% CI 0.82-1.72) for isolated OC, 2.37 (95% CI 1.54-3.43) for CP, and 1.86 (95% CI 1.07-2.94) for isolated CP. The distribution of other nonchromosomal malformation types with LTG exposure was similar to non-AED exposed. CONCLUSION: We find no evidence of a specific increased risk of isolated orofacial clefts relative to other malformations due to lamotrigine (LTG) monotherapy. Our study is not designed to assess whether there is a generalized increased risk of malformations with LTG exposure.