A novel astrovirus associated with encephalitis and ganglionitis in domestic sheep

In June 2013, a 4‐year‐old Welsh Mountain ewe and in March 2014 a 10‐day‐old lamb of the same breed and the same flock presented progressive neurological signs including depressed sensorium, tremor, and unusual behaviour. Neuropathological examination of the brain and spinal cord detected non‐suppurative polioencephalomyelitis and dorsal root ganglionitis, characteristic of a neurotropic viral agent in both sheep. Metagenomic analysis of different tissue samples from both animals identified a novel Ovine Astrovirus (OvAstV). The presence of viral genome in the central nervous system was confirmed by RT‐qPCR. Although the cases presented nine months apart, the identified OvAstV shared nearly identical sequences, differing in only three nucleotide positions across the complete genome. Phylogenetic analysis revealed a close relation of OvAstV to neurotropic bovine astroviruses and an enteric OvAstV. In conclusion, these are the first reported cases of astrovirus infection in domestic sheep that were associated with encephalitis and ganglionitis.     

Pemphigus vulgaris: a case-based update

Pemphigus vulgaris (PV) is an autoimmune disease accounting for 80% of all cases of pemphigus. Before the advent of corticosteroid therapy, pemphigus was fatal, with a mortality rate of up to 75% in the first year. It is still a serious disorder, but the 5% to 10% mortality rate is now primarily due to the side effects of therapy. In 75% to 80% of cases, PV lesions first appear in the oral cavity. Dentists are therefore in a unique position to recognize the oral manifestations of the disease, allowing early diagnosis and initiation of treatment. The diagnosis is based on pathological examination and immunofluorescence testing. Systemic corticosteriods and steroid-sparing agents are the mainstays of treatment; topical corticosteroids may also be used to accelerate healing of persistent oral lesions. This article describes a 71-year-old woman with multiple chronic ulcers in the oral cavity, in whom PV was diagnosed 4 months after the symptoms first appeared. The article also reviews the current literature on diagnosis and treatment of the condition.     

Optimal use of growth hormone therapy for maximizing adult height in children born small for gestational age

Growth retardation is a well-known complication of being born small for gestational age (SGA). Approximately 10% of children born SGA do not experience postnatal catch-up growth and are at risk for short adult height. The use of growth hormone (GH) therapy in these short children appears to increase their adult height, but modalities of GH administration remain controversial. Numerous therapeutic strategies have been developed to optimize the efficacy of GH treatment. Data concerning the influence of age at start of GH treatment, duration of GH treatment, GH dosage and method of GH administration on height gain and adult height are reported in this chapter. Longitudinal studies addressing the safety of GH treatment in SGA children are reassuring, but long-term follow-up remains necessary. Recommendations on the management of SGA children during GH treatment are given.     

Plasma N-terminal Pro-Brain Natriuretic Peptide (Nt-proBNP) level and prognosis after myocardial infarction in diabetes

Plasma N-terminal Pro-Brain Natriuretic Peptide (Nt-proBNP) level has been shown to provide valuable prognostic information on short and long-term mortality in patients with acute Myocardial Infarction, in the general population. Increased plasma Nt-proBNP levels have been found in Type 2 diabetic patients with vascular complications or with hypertension. In a large prospective study performed in 560 patients hospitalized for acute Myocardial Infarction (RICO), we found that median Nt-proBNP levels were significantly higher in the 199 diabetic patients compared to the 361 non-diabetic patients (245 (81-77) vs. 130 (49-199) pmol/L, P<0.0001). This difference remained highly significant after adjustment for confounding factors and we have been able to show that diabetes, per se, was a strong and independent factor for increased plasma Nt-proBNP levels, in this population. In the prospective RICO survey, we have found, in multivariable analysis, that diabetes was an independent factor for in-hospital mortality (OR: 1.79 [1.45-2.20]; P=0.0064) and cardiogenic shock (OR: 1.45(1.22-1.72); P =0.0364) when the variable Nt-proBNP level was not introduced into the model, but was less significantly associated with mortality (OR: 1.73 (1.39-2.16); P=0.0107) and no longer associated with cardiogenic shock when Nt-proBNP was in the model. This data suggest that increased plasma Nt-proBNP may be one of the links between diabetes and poor short-term prognosis after Myocardial Infarction and provides highly valuable prognostic information on in-hospital outcome in diabetic patients.     

Dual effect of cell-cell contact disruption on cytosolic calcium and insulin secretion

Cell-to-cell interactions play an important role in insulin secretion. Compared with intact islets, dispersed pancreatic beta-cells show increased basal and decreased glucose-stimulated insulin secretion. In this study, we used mouse MIN6B1 cells to investigate the mechanisms that control insulin secretion when cells are in contact with each other or not. RNAi-mediated silencing of the adhesion molecule E-cadherin in confluent cells reduced glucose-stimulated secretion to the levels observed in isolated cells but had no impact on basal secretion. Dispersed cells presented high cytosolic Ca(2+) activity, depolymerized cytoskeleton and ERK1/2 activation in low glucose conditions. Both the increased basal secretion and the spontaneous Ca(2+) activity were corrected by transient removal of Ca(2+) or prolonged incubation of cells in low glucose, a procedure that restored the ability of dispersed cells to respond to glucose (11-fold stimulation). In conclusion, we show that dispersed pancreatic beta-cells can respond robustly to glucose once their elevated basal secretion has been corrected. The increased basal insulin secretion of dispersed cells is due to spontaneous Ca(2+) transients that activate downstream Ca(2+) effectors, whereas engagement of cell adhesion molecules including E-cadherin contributes to the greater secretory response to glucose seen in cells with normal intercellular contacts.     

Prevalence of drug-drug interactions at hospital entry and during hospital stay of patients in internal medicine

OBJECTIVE: The aim of this study was to assess potential drug-drug interactions (pDDIs) at hospital admission, during hospitalization and at discharge and to evaluate the number of pDDIs created during hospitalization. METHODS: The medication of 851 patients was screened for pDDIs (major and moderate severity) using the screening program Pharmavista. The frequency of pDDIs per patient, per number of drugs and drug pairs was estimated. RESULTS: During hospitalization, the frequency of major and moderate pDDIs per patient was 1.11, which was higher compared to hospital admission (0.59) or to hospital discharge (0.60). The frequency of major and moderate pDDIs per drug prescribed (13.7% vs. 9.1%) or per drug pairs analyzed (4.5% vs. 2.3%) was higher at hospital admission compared to hospital discharge. 47% of all major and moderate pDDIs at discharge were due to a medication change during hospitalization. CONCLUSIONS: Although the number of major and moderate pDDIs per patient did not increase from hospital admission to discharge, it is important to realize that 47% of all major and moderate DDIs at hospital discharge were created during hospitalization. Prescribing drugs with a low risk for pDDIs as well as careful monitoring for adverse drug reactions are important measures to minimize harm associated with DDIs.