Clinical features,exercise hemodynamics,and determinants of left ventricular elevated filling pressure in heart‐transplanted patients

This study aimed to assess clinical, functional, and hemodynamic characteristics of heart‐transplanted (HTX) patients during exercise. We performed comprehensive echocardiographic graft function assessment during invasive hemodynamic semi‐supine exercise test in 57 HTX patients. According to hemodynamics findings, patients were divided into Group A: normal left ventricular (LV) filling pressure (FP): pulmonary capillary wedge pressure (PCWP) <15 mmHg at rest and <25 mmHg at peak exercise, and Group B: elevated LV‐FP: PCWP ≥15 mmHg at rest or ≥25 mmHg at peak exercise. Thirty‐one patients (54%) had normal LV‐FP and 26 patients (46%) had elevated LV‐FP. The latter had higher cumulative rejection burden (P < 0.01) and were more symptomatic (NYHA class >1) (P < 0.05), and cardiac allograft vasculopathy (CAV) was more prevalent (P < 0.05). With exercise, the changes in both left‐ and right‐sided filling pressures were significantly increased, whereas LV longitudinal myocardial deformation was lower (P < 0.05) in patients with elevated LV‐FP than in patients with normal LV‐FP. No between‐group difference was observed for cardiac index or LV ejection fraction (LVEF) during exercise. In conclusion, elevated LV‐FP can be demonstrated in approximately 50% of HTX patients. Patients with elevated LV‐FP have impaired myocardial deformation capacity, higher prevalence of CAV, and higher rejection burden, and were more symptomatic. Exercise test with the assessment of longitudinal myocardial deformation should be considered in routine surveillance of HTX patients as a marker of restrictive filling (ClinicalTrials.gov Identifier: NCT02077764).     

Microevolution and patterns of dissemination of the JP2 clone of Aggregatibacter (Actinobacillus) actinomycetemcomitans

The natural history, microevolution, and patterns of interindividual transmission and global dissemination of the JP2 clone of Aggregatibacter (Actinobacillus) actinomycetemcomitans were studied by population genetic analysis. The JP2 clone is strongly associated with aggressive periodontitis in adolescents of African descent and differs from other clones of the species by several genetic peculiarities, including a 530-bp deletion in the promoter region of the leukotoxin gene operon, which results in increased leukotoxic activity. Multilocus sequence analysis of 82 A. actinomycetemcomitans strains, 66 of which were JP2 clone strains collected over a period of more than 20 years, confirmed that there is a clonal population structure with evolutionary lineages corresponding to serotypes. Although genetically highly conserved, as shown by alignment of sequences of eight housekeeping genes, strains belonging to the JP2 clone had a number of point mutations, particularly in the pseudogenes hbpA and tbpA. Characteristic mutations allowed isolates from individuals from the Mediterranean area and from West Africa, including the Cape Verde Islands, to be distinguished. The patterns of mutations indicate that the JP2 clone initially emerged as a distinct genotype in the Mediterranean part of Africa approximately 2,400 years ago and subsequently spread to West Africa, from which it was transferred to the American continents during the transatlantic slave trade. The sustained exclusive colonization of individuals of African descent despite geographical separation for centuries suggests that the JP2 clone has a distinct host tropism. The colonization of family members by JP2 clone strains with unique point mutations provides strong evidence that there is intrafamilial transmission and suggests that dissemination of the JP2 clone is restricted to close contacts.     

Using mobile technology to overcome language barriers in medicine

Australia has a large migrant population with variable fluency in English. Interpreting services help ensure that healthcare services are delivered appropriately to these populations. However, the use of professional interpreters in hospitals is expensive. There are also issues with service availability and convenience. Mobile devices containing software with translating abilities have promising potential to improve communication between patients and hospital staff as an adjunct to professional interpreters. It is highly convenient and inexpensive. There are concerns about the accuracy of the interpretation done with such software and more research needs to be carried out to support or allay these concerns. For now, clinically important and medicolegal related interpretation should be undertaken by professional interpreters whereas less crucial tasks may be performed with the help of interpreting software on mobile devices.     

Thrombin causes subsecond changes in protein phosphorylation of platelets

We have developed a general quenched-flow approach to study platelet function as early as 0.3 seconds after stimulation. Phosphorylation of 20- and 40-kd proteins has been analyzed during the first five seconds of platelet response to thrombin from 0.1 to 5.0 U/mL and compared with the progress of aggregation and serotonin secretion. The onset time for aggregation and phosphorylation of both proteins was less than one second, although with lowest (less than 0.5 U/mL) thrombin levels, a lag of up to 0.6 seconds occurred before 40K phosphorylation increased. The thrombin sensitivity of aggregation and 20K phosphorylation was approximately twice that of 40K phosphorylation, with Ka values of 0.51 and 0.53 v 1.10 U/mL, respectively. External calcium was necessary for maximal 20K phosphorylation, since EDTA inhibited this by 30%. The 40K phosphorylation was not affected by EDTA. Platelet activation by thrombin thus induced biochemical changes well before one second. The quenched-flow approach may help to reveal relationships between phospholipase activation, calcium fluxes, and protein phosphorylation during these early periods of platelet function.     

Effect of vasoactive intestinal polypeptide and somatostatin on secretion of epidermal growth factor and bicarbonate from Brunner''s glands

The effect of VIP and somatostatin on secretion of epidermal growth factor and bicarbonate from Brunner's glands was investigated in the rat. Vasoactive intestinal polypeptide infused in doses of 10 and 100 ng/kg/h significantly increased epidermal growth factor and bicarbonate output, but the concentrations did not change. Somatostatin infused at doses of 1, 10, 100 and 1000 ng/kg/h against a background of VIP 100 ng/kg/h inhibited in dose-dependent fashion the stimulated epidermal growth factor and bicarbonate outputs from rat Brunner's gland pouches. Also basal secretion was inhibited by somatostatin. Infusion of antisomatostatin serum stimulated Brunner's gland secretion. By immunohistochemical studies of rat duodena, it was found that epidermal growth factor, is almost exclusively present in the secretory cells of Brunner's glands. It is concluded that VIP stimulates secretion of epidermal growth factor and bicarbonate from Brunner's glands, an effect which is inhibited by somatostatin. A possible role for somatostatin in the control of Brunner's gland secretion is suggested.