Risk factors for wheezing during infancy. A study of 5,953 infants

Risk factors for the development of wheezing during infancy were studied in 5,953 children. The data for the study were collected from a large prospective investigation of children born in 1959-61, who had attended a one-year follow-up examination. Wheezing was diagnosed when the symptom had been observed at least once during the first year of life, not in conjunction with pneumonia, epiglottitis or acute laryngitis. Logit analysis was used for the purpose of assessing the causal effect of environmental and other factors on the risk of wheezing among infants. The assessment of a risk factor by means of regression technique, requires certain other variables to be included in the regression model. A general rule concerning inclusion of other variables has been formulated and applied to the above data. The study demonstrated that the risk of wheezing was affected by a number of factors--particularly environmental. Poor social environment increases the risk of wheezing, as does the mother's smoking, and placement of the baby in day-care. Boys experienced wheezing more often than girls. Premature infants are more liable to develop wheezing than mature children. Remarkably, children born in the period April through September develop wheezing, but not bronchitis, more often than children born in October through March.     

A polymorphic major histocompatibility complex class II‐like locus maps outside of both the chicken B‐system and Rfp‐Y‐system

Chickens have two major regions encoding major histocompatibility complex (MHC) class Iα genes and MHC class IIß genes, the serological and functional B‐system and the Rfp‐Y‐system. Recently, they have been shown to assort in a genetically independent way although still located on the same microchromosome. Moreover, the monomorphic MHC class IIα gene maps at a third locus located 5 c m from the nearest class IIß genes, located in the B‐system ( Kaufman et al., 1995 ). A pedigree family was studied in three generations in order to assign MHC class IIß restriction fragments observed in Southern blot analyses to either the B‐system, the Rfp‐Y‐system or the B‐Lα locus. In this study, we demonstrate by classical genetic testing of chickens within this fully pedigreed family the existence of an MHC class II‐like polymorphic restriction fragment that segregates independently of the B‐system, the Rfp‐Y‐system and of the B‐Lα locus.     

Intermediate expansions of a GAA repeat in the frataxin gene are not associated with type 2 diabetes or altered glucose-induced beta-cell function in Danish Caucasians

A variable expansion of a GAA repeat is present in the first intron of the frataxin gene, also termed FRDA1 or X25. Long repeat lengths (>66 repeats) are present in patients with Friedreich's ataxia, while an intermediate expansion (10-66 repeats) has recently been reported to be highly associated with type 2 diabetes. Using a polymerase chain reaction-based assay, we found that 32.4% (95%CI 29.9-34.9) of 636 Danish Caucasian type 2 diabetic patients were carriers of an intermediate expansion, whereas the frequency was 30.4% (26.4-34.4) among 224 matched glucose-tolerant control subjects (P = 0.6). In the control subjects, the values of serum insulin and C-peptide responses during an oral glucose tolerance test were similar between the 69 carriers and 155 noncarriers. Furthermore, we investigated a possible relationship between expansions of the FRDA1 gene and glucose-induced beta-cell function in 338 young Caucasians (33.7% [30.1-37.3] carriers) and in 215 glucose-tolerant subjects (31.0% [26.6-35.4] carriers) with a type 2 diabetic parent. In neither population did the carriers differ from noncarriers according to values of fasting plasma glucose, serum insulin, or C-peptide, acute serum insulin, or C-peptide responses after intravenous glucose. In conclusion, intermediate expansion of the frataxin trinucleotide repeat is not associated with type 2 diabetes or altered glucose-induced insulin secretion in Danish Caucasians.     

Metabolism and excretion of citalopram in man: identification of O-acyl- and N-glucuronides

The antidepressant citalopram (CT), a selective serotonin uptake inhibitor, was given in its labelled form, [14C]-CT, as a single oral dose in 50 ml aqueous solution (0.1 mmol/30 microCi/1.1 MBq) to four healthy male volunteers. Concentrations of radioactivity in whole blood and plasma were similar. The respective pharmacokinetic parameters were: Cmax = 214+/-41 and 246+/-69 nmol eq./litre, Tmax = 3 and 2 h, AUC = 18289+/-2959 and 14537+/-2883 nmol eq. h/litre, and t1/2 = 90.2+/-22.5 and 79.5 +/- 14.9 h respectively. A mean of 85.2 +/- 10.4% of the radioactive dose was recovered after 17 days of collection of excreta. The majority of radioactivity was excreted in urine (74.7+/-8.9%) and the remaining part in faeces (10.5+/-2.3%). The HPLC profile of urinary components showed that besides the known metabolites of citalopram, three glucuronides were present. The relative amounts of CT and its metabolites in urine collected for 7 days were: CT (26 %), N-demethyl-CT (DCT, 19%), N,N-didemethyl-CT (DDCT,9%), the N-oxide (7%), the quaternary ammonium glucuronide of CT (CT-GLN, 14%), the N-glucuronide of DDCT (DDCT-GLN, 6%), and the glucuronide of the acid metabolite (CT-acid-GLN, 12%) formed by N,N-dimethyl deamination of CT. CT-GLN was isolated using preparative chromatography and identified by LC-MS-MS and NMR. DDCT-GLN and CT-acid-GLN were identified by LC-MS. This study shows that protracted renal excretion represents the major route of elimination, with a small fraction voided with faeces. A considerable portion of the urinary excreted dose consists of N-glucuronides of CT and DDCT together with the O-acyl glucuronide of CT-acid.     

Perinatal exposure to the fungicide prochloraz feminizes the male rat offspring.

Prochloraz is a commonly used fungicide that has shown multiple mechanisms of action in vitro. It antagonizes the androgen and the estrogen receptors, agonizes the Ah receptor, and inhibits aromatase activity. In vivo prochloraz acts antiandrogenically in the Hershberger assay by reducing weights of reproductive organs, affecting androgen-regulated gene expressions, and increasing luteinizing hormone (LH) levels. The purpose of this study was to investigate reproductive toxic effects after exposure during gestation and lactation to prochloraz alone and a mixture of five pesticides (deltamethrin, methiocarb, prochloraz, simazine, and tribenuron-methyl). Prochloraz (30 mg/kg/day) or the mixture (20 mg/kg/day) was dosed to pregnant Wistar dams from gestational day (GD) 7 until postnatal day (PND) 16. Some dams were taken for cesarean section at GD 21, and others were allowed to give birth. Results showed that prochloraz and the mixture significantly reduced plasma and testicular testosterone levels in GD 21 male fetuses, whereas testicular progesterone was increased. Gestational length was increased by prochloraz. Chemical analysis of the rat breast milk showed that prochloraz was transferred to the milk. In males a significant increase of nipple retention was found, and the bulbourethral gland weight was decreased, whereas other reproductive organs were unaffected. In addition cytochrome P450 (CYP)1A activities in livers were induced by prochloraz, possibly as a result of Ah receptor activation. Behavioral studies showed that the activity level and sweet preference of adult males were significantly increased. Overall these results strongly indicate that prochloraz feminizes the male offspring after perinatal exposure, and that these effects are due, at least in part, to diminished fetal steroidogenesis.     

Human Parechovirus Infection,Denmark

Human parechoviruses (HPeVs) often cause severe illness among young children. National surveillance with routine testing of all cerebrospinal fluid, fecal, and tissue samples was conducted during January 2009–December 2012 in all counties in Denmark (6,817 samples from 4,804 children were screened for HPeV). We detected HPeV RNA in 202 (3.0%) specimens from 149 persons. Young infants were at highest risk for HPeV, and 9 (6%) of the HPeV-infected children died, probably of their HPeV illness. HPeV3 was the most common genotype identified, and 5 closely related clades of HPeV3 circulated in Denmark throughout the study period. Our study adds perspective on the prevalence and clinical and molecular virologic characteristics of HPeV infection.     

No protection in chickens immunized by the oral or intra-muscular immunization route with Ascaridia galli soluble antigen

In chickens, the nematode Ascaridia galli is found with prevalences of up to 100% causing economic losses to farmers. No avian nematode vaccines have yet been developed and detailed knowledge about the chicken immune response towards A. galli is therefore of great importance. The objective of this study was to evaluate the induction of protective immune responses to A. galli soluble antigen by different immunization routes. Chickens were immunized with a crude extract of A. galli via an oral or intra-muscular route using cholera toxin B subunit as adjuvant and subsequently challenged with A. galli. Only chickens immunized via the intra-muscular route developed a specific A. galli antibody response. Frequencies of γδ T cells in spleen were higher 7 days after the first immunization in both groups but only significantly so in the intra-muscularly immunized group. In addition, systemic immunization had an effect on both Th1 and Th2 cytokines in caecal tonsils and Meckel's diverticulum. Thus both humoral and cellular immune responses are inducible by soluble A. galli antigen, but in this study no protection against the parasite was achieved.     

Update in Outpatient General Internal Medicine: Practice-Changing Evidence Published in 2020

In a time of rapidly shifting evidence-based medicine, it is challenging to stay informed of research that modifies clinical practice. To enhance knowledge of practice-changing literature, a group of 7 internists reviewed titles and abstracts in 7 internal medicine journals with the highest impact factors and relevance to outpatient general internal medicine. Coronavirus disease-19 research was purposely excluded to highlight practice changes beyond the pandemic. New England Journal of Medicine (NEJM), The Lancet, Annals of Internal Medicine, Journal of the American Medical Association (JAMA), JAMA Internal Medicine, British Medical Journal (BMJ), and Public Library of Science (PLoS) Medicine were reviewed. The following collections of article synopses and databases were also reviewed: American College of Physicians Journal Club, NEJM Journal Watch, BMJ Evidence-Based Medicine, McMaster/DynaMed Evidence Alerts, and Cochrane Reviews. A modified Delphi method was used to gain consensus based on relevance to outpatient internal medicine, impact on practice, and strength of evidence. Clusters of articles pertaining to the same topic were considered together. In total, 7 practice-changing articles were included.     

Urological symptoms among 23,240 men in the general danish population – concerns about symptoms,their persistence and influence on primary care contacts

Objective: To analyse possible associations between men’s likelihood of contacting a general practitioner (GP) for urological symptoms and the persistence of the symptoms, the influence on daily activities and the level of concern about the symptoms.

Design: Web-based nationwide cross-sectional questionnaire study.

Setting: The general population in Denmark.

Subjects: 48,910 randomly selected men aged 20+ years.

Main outcome measures: Urological symptom prevalence and odds ratios for GP contact with urological symptoms in regard to concern for the symptom, influence on daily activities and the persistence of the symptom.

Results: Some 23,240 men responded to the questionnaire, yielding a response rate of 49.8%. The prevalence of at least one urological symptom was 59.9%. Among men experiencing at least one urological symptom almost one-fourth reported contact to general practice regarding the symptom. Approximately half of the symptoms reported to be extremely concerning were discussed with a GP.

Conclusion: Increased symptom concern, influence on daily activities and long-term persistence increased the likelihood of contacting a GP with urological symptoms. This research points out that guidelines for PSA testing might be challenged by the high prevalence of urological symptoms.

• Key points

• ?The decision process of whether to contact the general practitioner (GP) is influenced by different factors, but contradictory results has been found in triggers and barriers for help-seeking with urological symptoms.

• ??Increased symptom concern, influence on daily activities and long-term persistence consistently increased the likelihood of contacting a general practitioner with urological symptoms in men.

• ??Only 50% of the symptoms reported to be extremely concerning were however discussed with the GP.

• ??Guidelines for PSA testing might be challenged by the high prevalence of urological symptoms.