Is the DHEAS/cortisol ratio a potential filter for non-operable constipated cases?

Constipation is a significant manifestation of a number of psychological disorders.Published papers recommend using self-assessment questionnaires for discriminating psychological from non-psychological constipated patients before operating on them but reports from major surveys revealed that general practitioners failed to diagnose 70%of depressed patients using self-assessment questionnaires.Lower circulating concentrations of progesterone,17-hydroxyprogesterone,cortisol,testosterone,androstenedione,and d...     

Sequence variants in the HLX gene at chromosome 1q41-1q42 in patients with diaphragmatic hernia

Congenital diaphragmatic hernia (CDH) is a common birth defect for which few causative genes have been identified. Several candidate regions containing genes necessary for normal diaphragm development have been identified, including a 4–5 Mb deleted region at chromosome 1q41-1q42 from which the causative gene(s) has/have not been cloned. We selected the HLX gene from this interval as a candidate gene for CDH, as the Hlx homozygous null mouse has been reported to have diaphragmatic defects and the gene was described as being expressed in the murine diaphragm. We re-sequenced HLX in 119 CDH patients and identified four novel single nucleotide substitutions that predict amino acid changes: p.S12F, p.S18L, p.D173Y and p.A235V. These sequence alterations were all present in patients with isolated CDH, although patients with both isolated CHD and CDH with additional anomalies were studied. The single-nucleotide substitutions were absent in more than 186 control chromosomes. In-situ hybridization studies confirmed expression of Hlx in the developing murine diaphragm at the site of the junction of the diaphragm and the liver. Although functional studies to determine if these novel sequence variants altered the inductive activity of Hlx on the α-smooth muscle actin and SM22α promoters showed no significant differences between the variants and wild-type Hlx , sequence variants in HLX may still be relevant in the pathogenesis of CDH in combination with additional genetic and environmental factors.     

Chromosome imbalances in syndromic hearing loss

The cause of hearing impairment has not been elucidated in a large proportion of patients. We screened by 1-Mb array-based comparative genomic hybridization (aCGH) 29 individuals with syndromic hearing impairment whose clinical features were not typical of known disorders. Rare chromosomal copy number changes were detected in eight patients, four de novo imbalances and four inherited from a normal parent. The de novo alterations define candidate chromosome segments likely to harbor dosage-sensitive genes related to hearing impairment, namely 1q23.3–q25.2, 2q22q23, 6p25.3 and 11q13.2–q13.4. The rare imbalances also present in normal parents might be casually associated with hearing impairment, but its role as a predisposition gene remains a possibility. Our results show that syndromic deafness is frequently associated with chromosome microimbalances (14–27%), and the use of aCGH for defining disease etiology is recommended.     

Changes in General Nurses' Knowledge of Alcohol and Substance Use and Misuse After Education

PURPOSE.  This study aims to assess the impact of an education program on Australian general nurses' knowledge and competence in identifying and managing patients with alcohol and substance use and misuse, and compare findings with existing literature on mental health nurses.
DESIGN AND METHODS.  Pre- and posttest design without a control group.
FINDINGS.  The nurses' knowledge of safe drinking limits and alcohol withdrawal management improved following the education. Nevertheless, overall the nurses reported a lack of adequate knowledge and competence. Compared to mental health nurses, the nurses in this study had lower levels of knowledge and competence.
PRACTICE IMPLICATIONS.  We suggest several opportunities for general nurses to strengthen their knowledge and skills and the need for a comprehensive and regular education program.     

In vitro and in vivo pharmacological role of TLQP-21, a VGF-derived peptide,in the regulation of rat gastric motor functions

Background and purpose:

Vgf gene expression has been detected in various endocrine and neuronal cells in the gastrointestinal tract. In this study we investigated the pharmacological activity of different VGF-derived peptides. Among these, TLQP-21, corresponding to the 556–576 fragment of the protein was the unique active peptide, and its pharmacological profile was further studied.

Experimental approach:

The effects of TLQP-21 were examined in vitro by smooth muscle contraction in isolated preparations from the rat gastrointestinal tract and, in vivo, by assessing gastric emptying in rats. Rat stomach tissues were also processed for immunohistochemical and biochemical characterization.

Key results:

In rat longitudinal forestomach strips, TLQP-21 (100 nmol·L⁻¹–10 µmol·L⁻¹) concentration-dependently induced muscle contraction (in female rats, EC₅₀ = 0.47 µmol·L⁻¹, E_max: 85.7 ± 7.9 and in male rats, 0.87 µmol·L⁻¹, E_max: 33.4 ± 5.3; n = 8), by release of prostaglandin (PG)E₂ and PGF_2a from the mucosal layer. This effect was significantly antagonized by indomethacin and selective inhibitors of either cyclooxygenase-1 (S560) or cyclooxygenase-2 (NS398). Immunostaining and biochemical studies confirmed the presence of VGF in the gastric neuronal cells. TLQP-21, injected i.c.v. (2–32 nmol per rat), significantly decreased gastric emptying by about 40%. This effect was significantly (P < 0.05) blocked by i.c.v. injection of indomethacin, suggesting that, also in vivo, this peptide acts in the brain stimulating PG release.

Conclusions and implications:

The present results demonstrate that this VGF-derived peptide plays a central and local role in the regulation of rat gastric motor functions.     

Pals-associated tight junction protein functionally links dopamine and angiotensin II to the regulation of sodium transport in renal epithelial cells

Background and purpose:

Dopamine inhibits renal cell Na⁺,K⁺-ATPase activity and cell sodium transport by promoting the internalization of active molecules from the plasma membrane, whereas angiotensin II (ATII) stimulates its activity by recruiting new molecules to the plasma membrane. They achieve such effects by activating multiple and distinct signalling molecules in a hierarchical manner. The purpose of this study was to investigate whether dopamine and ATII utilize scaffold organizer proteins as components of their signalling networks, in order to avoid deleterious cross talk.

Experimental approach:

Attention was focused on a multiple PDZ domain protein, Pals-associated tight junction protein (PATJ). Ectopic expression of PATJ in renal epithelial cells in culture was used to study its interaction with components of the dopamine signalling cascade. Similarly, expression of PATJ deletion mutants was employed to analyse its functional relevance during dopamine-, ATII- and insulin-dependent regulation of Na⁺,K⁺-ATPase.

Key results:

Dopamine receptors and components of its signalling cascade mediating inhibition of Na⁺,K⁺-ATPase interact with PATJ. Inhibition of Na⁺,K⁺-ATPase by dopamine was prevented by expression of mutants of PATJ lacking PDZ domains 2, 4 or 5; whereas the stimulatory effect of ATII and insulin on Na⁺,K⁺-ATPase was blocked by expression of PATJ lacking PDZ domains 1, 4 or 5.

Conclusions and implications:

A multiple PDZ domain protein may add functionality to G protein-coupled and tyrosine kinase receptors signalling during regulation of Na⁺,K⁺-ATPase. Signalling molecules and effectors can be integrated into a functional network by the scaffold organizer protein PATJ via its multiple PDZ domains.     

Experience as a doctor in the developing world: does it benefit the clinical and organisational performance in general practice?

Background

Lipid-lowering medication remains underused, even in high-risk populations. The objective of this study was to determine factors underlying general practitioners' decisions not to prescribe such drugs to patients with type 2 diabetes.

Methods

A qualitative study with semi-structured interviews using real cases was conducted to explore reasons for not prescribing lipid-lowering medication after a guideline was distributed that recommended the use of statins in most patients with type 2 diabetes. Seven interviews were conducted with general practitioners (GPs) in The Netherlands, and analysed using an analytic inductive approach.

Results

Reasons for not-prescribing could be divided into patient and physician-attributed factors. According to the GPs, some patients do not follow-up on agreed medication and others object to taking lipid-lowering medication, partly for legitimate reasons such as expected or perceived side effects. Furthermore, the GPs themselves perceived reservations for prescribing lipid-lowering medication in patients with short life expectancy, expected compliance problems or near goal lipid levels. GPs sometimes postponed the start of treatment because of other priorities. Finally, barriers were seen in the GPs' practice organisation, and at the primary-secondary care interface.

Conclusion

Some of the barriers mentioned by GPs seem to be valid reasons, showing that guideline non-adherence can be quite rational. On the other hand, treatment quality could improve by addressing issues, such as lack of knowledge or motivation of both the patient and the GP. More structured management in general practice may also lead to better treatment.