Acute small bowel obstruction as a result of a Meckel's diverticulum encircling the terminal ileum: A case report

BACKGROUND: In the developed world, small bowel obstruction accounts for 20% of all acute surgical admissions. The aetiology for majority of these cases includes postoperative adhesions and herniae. However, a relatively uncommon cause is a Meckel's diverticulum. Although this diagnosis is primarily reported in the adolescent population, it should also be considered in adults. CASE PRESENTATION: In the present report, we present a rare case where a fit and healthy 74-year-old gentleman, with no previous history of abdominal surgery, presented with the cardinal symptoms and signs of small bowel obstruction as the result of a Meckel's diverticulum encircling his terminal ileum. Initial investigations included a supine abdominal x-ray showing dilated loops of small bowel and computerised tomographic imaging of the abdomen, which revealed a stricture in the terminal ileum of unknown aetiology. At laparotomy, multiple loops of distended small bowel were seen from the duodeno-jeujenal junction to the terminal ileum, which was encircled by a Meckel's diverticulum. The Meckel's diverticulum was then divided to release the obstruction, mobilised and subsequently removed. Finally, the small bowel contents were decompressed into the stomach and the nasogastric tube aspirated, before returning the loops of bowel into the abdomen in sequence. The patient made a good postoperative recovery and was discharged home 5 days later. CONCLUSION: This report highlights the importance of considering a Meckel's diverticulum as a cause of small bowel obstruction in individuals from all age groups and especially in a person with no previous abdominal pathology or surgery

Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes

The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders

TRH: Pathophysiologic and clinical implications

Thyrotropin releasing hormone is thought to be a tonic stimulator of the pituitary TSH secretion regulating the setpoint of the thyrotrophs to the suppressive effect of thyroid hormones. The peptide stimulates the release of normal and elevated prolactin. ACTH and GH may increase in response to exogenous TRH in pituitary ACTH and GH hypersecretion syndromes and in some extrapituitary diseases. The pathophysiological implications of extrahypothalamic TRH in humans are essentially unknown. The TSH response to TRH is nowadays widely used as a diganostic amplifier in thyroid diseases being suppressed in borderline and overt hyperthyroid states and increased in primary thyroid failure. In hypothyroid states of hypothalamic origin, TSH increases in response to exogenous TRH often with a delayed and/or exaggerated time course. But in patients with pituitary tumors and suprasellar extension TSH may also respond to TRH despite secondary hypothyroidism. This TSH increase may indicate a suprasellar cause for the secondary hypothyroidism, probably due to portal vessel occlusion. The TSH released in these cases is shown to be biologically inactive

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

Increasing capacity for the treatment of common musculoskeletal problems: A non-inferiority RCT and economic analysis of corticosteroid injection for shoulder pain comparing a physiotherapist and orthopaedic surgeon

Background Role substitution is a strategy employed to assist health services manage the growing demand for musculoskeletal care. Corticosteroid injection is a common treatment in this population but the efficacy of its prescription and delivery by physiotherapists has not been established against orthopaedic standards. This paper investigates whether corticosteroid injection given by a physiotherapist for shoulder pain is as clinically and cost effective as that from an orthopaedic surgeon. Methods A double blind non-inferiority randomized controlled trial was conducted in an Australian public hospital orthopaedic outpatient service, from January 2013 to June 2014. Adults with a General Practitioner referral to Orthopaedics for shoulder pain received subacromial corticosteroid and local anaesthetic injection prescribed and delivered independently by a physiotherapist or a consultant orthopaedic surgeon. The main outcome measure was total Shoulder Pain and Disability Index (SPADI) score at baseline, six and 12 weeks, applying a non-inferiority margin of 15 points. Secondary outcomes tested for superiority included pain, shoulder movement, perceived improvement, adverse events, satisfaction, quality of life and costs. Results 278 participants were independently assessed by the physiotherapist and the orthopaedic surgeon, with 64 randomised (physiotherapist 33, orthopaedic surgeon 31). There were no significant differences in baseline characteristics between groups. Non-inferiority of injection by the physiotherapist was declared from total SPADI scores at 6 and 12 weeks (upper limit of the 95% one-sided confidence interval 13.34 and 7.17 at 6 and 12 weeks, respectively). There were no statistically significant differences between groups on any outcome measures at 6 or 12 weeks. From the perspective of the health funder, the physiotherapist was less expensive. Conclusions Corticosteroid injection for shoulder pain, provided by a suitably qualified physiotherapist is at least as clinically effective, and less expensive, compared with similar care delivered by an orthopaedic surgeon. Policy makers and service providers should consider implementing this model of care

Generation of Immortal Cell Lines from the Adult Pituitary: Role of cAMP on Differentiation of SOX2-Expressing Progenitor Cells to Mature Gonadotropes

The pituitary is a complex endocrine tissue composed of a number of unique cell types distinguished by the expression and secretion of specific hormones, which in turn control critical components of overall physiology. The basic function of these cells is understood; however, the molecular events involved in their hormonal regulation are not yet fully defined. While previously established cell lines have provided much insight into these regulatory mechanisms, the availability of representative cell lines from each cell lineage is limited, and currently none are derived from adult pituitary. We have therefore used retroviral transfer of SV40 T-antigen to mass immortalize primary pituitary cell culture from an adult mouse. We have generated 19 mixed cell cultures that contain cells from pituitary cell lineages, as determined by RT-PCR analysis and immunocytochemistry for specific hormones. Some lines expressed markers associated with multipotent adult progenitor cells or transit-amplifying cells, including SOX2, nestin, S100, and SOX9. The progenitor lines were exposed to an adenylate cyclase activator, forskolin, over 7 days and were induced to differentiate to a more mature gonadotrope cell, expressing significant levels of α-subunit, LHβ, and FSHβ mRNAs. Additionally, clonal populations of differentiated gonadotropes were exposed to 30 nM gonadotropin-releasing hormone and responded appropriately with a significant increase in α-subunit and LHβ transcription. Further, exposure of the lines to a pulse paradigm of GnRH, in combination with 17β-estradiol and dexamethasone, significantly increased GnRH receptor mRNA levels. This array of adult-derived pituitary cell models will be valuable for both studies of progenitor cell characteristics and modulation, and the molecular analysis of individual pituitary cell lineages

Natriuretic peptide activation of extracellular regulated kinase 1/2 (ERK1/2) pathway by particulate guanylyl cyclases in GH3 somatolactotropes.

The natriuretic peptides, Atrial-, B-type and C-type natriuretric peptides (ANP, BNP, CNP), are regulators of many endocrine tissues and exert their effects predominantly through the activation of their specific guanylyl cyclase receptors (GC-A and GC-B) to generate cGMP. Whereas cGMP-independent signalling has been reported in response to natriuretic peptides, this is mediated via either the clearance receptor (Npr-C) or a renal-specific NPR-Bi isoform, which both lack intrinsic guanylyl cyclase activity. Here, we report evidence of GC-B-dependent cGMP-independent signalling in pituitary GH3 cells. Stimulation of GH3 cells with CNP resulted in a rapid and sustained enhancement of ERK1/2 phosphorylation (P-ERK1/2), an effect that was not mimicked by dibutryl-cGMP. Furthermore, CNP-stimulated P-ERK1/2 occurred at concentrations below that required for cGMP accumulation. The effect of CNP on P-ERK1/2 was sensitive to pharmacological blockade of MEK (U0126) and Src kinases (PP2). Silencing of the GC-B1 and GC-B2 splice variants of the GC-B receptor by using targeted short interfering RNAs completely blocked the CNP effects on P-ERK1/2. CNP failed to alter GH3 cell proliferation or cell cycle distribution but caused a concentration-dependent increase in the activity of the human glycoprotein α-subunit promoter (αGSU) in a MEK-dependent manner. Finally, CNP also activated the p38 and JNK MAPK pathways in GH3 cells. These findings reveal an additional mechanism of GC-B signalling and suggest additional biological roles for CNP in its target tissues