The effects of remote ischaemic preconditioning on coronary artery function in patients with stable coronary artery disease.

BACKGROUND: Remote ischaemic preconditioning (RIPC) is a cardioprotective intervention invoking intermittent periods of ischaemia in a tissue or organ remote from the heart. The mechanisms of this effect are incompletely understood. We hypothesised that RIPC might enhance coronary vasodilatation by an endothelium-dependent mechanism. METHODS: We performed a prospective, randomised, sham-controlled, blinded clinical trial. Patients with stable coronary artery disease (CAD) undergoing elective invasive management were prospectively enrolled, and randomised to RIPC or sham (1:1) prior to angiography. Endothelial-dependent vasodilator function was assessed in a non-target coronary artery with intracoronary infusion of incremental acetylcholine doses (10-6, 10-5, 10-4mol/l). Venous blood was sampled pre- and post-RIPC or sham, and analysed for circulating markers of endothelial function. Coronary luminal diameter was assessed by quantitative coronary angiography. The primary outcome was the between-group difference in the mean percentage change in coronary luminal diameter following the maximal acetylcholine dose (Clinicaltrials.gov identifier: NCT02666235). RESULTS: 75 patients were enrolled. Following angiography, 60 patients (mean±SD age 57.5±8.5years; 80% male) were eligible and completed the protocol (n=30 RIPC, n=30 sham). The mean percentage change in coronary luminal diameter was -13.3±22.3% and -2.0±17.2% in the sham and RIPC groups respectively (difference 11.32%, 95%CI: 1.2- 21.4, p=0.032). This remained significant when age and sex were included as covariates (difference 11.01%, 95%CI: 1.01- 21.0, p=0.035). There were no between-group differences in endothelial-independent vasodilation, ECG parameters or circulating markers of endothelial function. CONCLUSIONS: RIPC attenuates the extent of vasoconstriction induced by intracoronary acetylcholine infusion. This endothelium-dependent mechanism may contribute to the cardioprotective effects of RIPC.

Detection of Trypanosoma cruzi DNA in blood by PCR is associated with Chagas cardiomyopathy and disease severity.

BACKGROUND: The significance of detection of Trypanosoma cruzi DNA in blood of antibody-positive patients for risk of development of Chagas heart disease is not well established. The objective of this study was to compare detection of T. cruzi DNA with known clinical and laboratory markers of Chagas cardiomyopathy (CC) severity. METHODS: This is a case-control study nested within a retrospective cohort developed in Brazil to understand the natural history of Chagas disease. The study enrolled 499 T. cruzi seropositive blood donors (SP-BD) and 488 frequency matched seronegative control donors (SN-BD) who had donated between 1996 and 2002, and 101 patients with clinically diagnosed CC. In 2008-2010 all enrolled subjects underwent a health questionnaire, medical examination, electrocardiograms and echocardiograms and polymerase chain reaction (PCR) analyses. A blinded panel of three cardiologists adjudicated the outcome of CC. Trypanosoma cruzi kinetoplast minicircle sequences were amplified by real-time PCR using an assay with a sensitivity of one parasite per 20 mL of blood. All testing was performed on coded samples. RESULTS: Rates of PCR detection of T. cruzi DNA were significantly (P = 0.003) higher in CC patients and SP-BD diagnosed with CC (79/105 [75.2 %]) compared with SP-BD without CC (143/279 [51.3%]). The presence of parasitaemia was significantly associated with known markers of disease progression such as QRS and QT interval duration, lower left ventricular ejection fraction, higher left ventricular index mass, and elevated troponin and NTpro-BNP levels. CONCLUSION: Trypanosoma cruzi PCR positivity is associated with presence and severity of cardiomyopathy, suggesting a direct role of parasite persistence in disease pathogenesis.

Human neutrophil antibodies in a blood donor population: a lookback study.

BACKGROUND AND OBJECTIVES: Human neutrophil antibodies (HNA) have been associated with severe transfusion-related acute lung injury (TRALI). We identified HNA antibodies in a blood donor population and performed an observational lookback on patients who received products from these donors to determine whether TRALI was associated with these transfusions. MATERIALS AND METHODS: Human neutrophil antibodies were determined in 1171 blood donors (388 non-transfused males, 390 human leucocyte antigen (HLA) antibody-negative females and 393 HLA antibody-positive females) for IgG and IgM antibodies using a flow cytometric assay. Selected positive samples had a monoclonal antibody immobilization of granulocyte antigen (MAIGA) and neutrophil genotyping performed to confirm specificity. Lookback was performed on patients receiving blood from donors with positive samples by extracting recipient data from hospital medical records. An expert panel of three pulmonary critical care physicians reviewed the summarized data and assigned a diagnosis of TRALI, possible TRALI, cannot distinguish between TRALI and TACO, TACO and other. RESULTS: Eight donors had HNA antibodies of which five contributed to this lookback (3-HNA-specific antibodies, 2-HNA non-specific antibodies). Seventy-six blood products were transfused from these donors into individual patients. One patient developed TRALI that was associated with a donor with a non-specific HNA antibody as well as class-I and class-II HLA antibodies. CONCLUSION: The incidence of TRALI in this lookback was low and combined with low frequency of HNA antibodies in the donor population suggests not screening donors for HNA antibodies at this time is acceptable.

Tympanoplasty surgery and prophylactic antibiotics: surgical results.

This paper reports a multicentre, controlled, blind, prospective, randomized study into the use of prophylactic systemic antibiotics in myringoplasty surgery. A total of 130 individuals were randomly allocated to either an antibiotic or a non-antibiotic group. Each individual was clinically and audiometrically assessed preoperatively, and 8 weeks postoperatively. It was found that systemic prophylactic antibiotics did not influence either the success rate of myringoplasty surgery or the audiometric result.

Systemic antibiotic prophylaxis and reconstructive ear surgery.

This paper reports a multicentre, controlled, blind, prospective, randomized study into the use of prophylactic systemic antibiotics in myringoplasty surgery. Seventy-one individuals were clinically and bacteriologically assessed both preoperatively, and for a period of 8 weeks postoperatively. The results showed that antibiotic prophylaxis did not eradicate bacterial pathogens already present in preoperative ears, nor did it prevent their development during the postoperative period. The observation that an ear was wet or dry gave no indication of the actual presence or absence of pathogenic organisms.

Low-powered ultrasound in the inhibition of tinnitus.

An experiment was performed using low-level ultrasound in an attempt to inhibit tinnitus during and after stimulation. The method used a double-blind crossover technique with a placebo. Forty subjects were tested, and they generally reported little or no change in their tinnitus, the results from placebo and ultrasound not being statistically different. It cannot be concluded, therefore, that the ultrasound we were using has any beneficial effect on tinnitus. These results do not confirm the findings of the pilot study using the same ultrasound devices (Carrick et al., 1986).

Low-powered ultrasound in the treatment of tinnitus: a pilot study.

The aim of this study was to determine whether a low dose of ultrasound, applied over the mastoid bone, caused a subjective improvement in the level of tinnitus in long standing tinnitus sufferers. Forty patients from the Swansea Tinnitus Association volunteered to take part in a double blind crossover trial. They received a 10-minute treatment with an ultrasound generator and an identical placebo device on two separate visits. The devices were randomly allocated on the first visit. At each visit the patient noted whether their tinnitus was completely improved, slightly improved, unchanged or made worse by the treatment. Forty per cent of patients who completed the trial were improved by ultrasound, 7% by placebo. Low powered ultrasound was significantly better at producing improvement than placebo (P less than 0.02 Binomial Test).

Salicylates and post-tonsillectomy haemorrhage.

A prospective study of 712 patients who had tonsillectomy by guillotine or dissection suggests that salicylates used as post-tonsillectomy analgesia increase the post-operative haemorrhage rate. Paracetamol used as post-operative analgesia was shown to be related to a significantly reduced haemorrhage rate. Guillotine tonsillectomy was not shown to have any adverse effect on the haemorrhage rate.

Metabolic significance of milk glucose.

The free glucose concentration in the aqueous phase of samples of goat, sheep, cow, rat and rabbit milk was about 0.1-0.3 mM, while that in human milk was about 2mM. During starvation the glucose concentration of goat milk fell considerably (by about 80% in 2 d) in parallel with the decreased rate of lactose production. With rats fed ad lib., glucose concentration in the milk was greater at 12.00 h than at 18.00 h, when lactose synthesis has been shown to decrease. 3-O-Methyl-D-glucose injected into the goat mammary gland via the teat canal specifically entered the blood. These findings support the idea that glucose equilibrates across the apical membrane of mammary secretory cells, so that milk concentrations reflect intracellular glucose concentratioins.

Lactose synthesis: the possibilities of regulation.

Elucidation of the details of lactose synthesis, in particular its dependence upon alpha-lactalbumin and its location within the lumen of the Golgi apparatus, now allows one to ask useful questions pertaining to its regulation. Attention is directed towards galactosyltransferase itself (EC 2.4.1.22), which appears to be rate-limiting in the uridine nucleotide cycle that supports lactose synthesis, and to those factors that may affect its activity. In laboratory animals alpha-lactalbumin appears to be the major agent of regulation during lactogenesis but is not necessarily limiting at other times, whereas the increase in amount of galactosyltransferase seems largely to account for the rising yield of lactose during lactation. Studies with pinched-off Golgi membrane vesicles, together with measurements of intracellular chemical concentrations, suggest that beta-glucose and uridine diphosphategalactose do not saturate lactose synthesis and are, therefore potentially regulatory features of this process. Further aspects of lactose synthesis that may offer points of regulation include calcium ions, generation of protons within the Golgi lumen, and the generally rate-limiting nature of the Golgi membrane.

Diurnal variation and response to food withdrawal of lactose synthesis in lactating rats.

1. The incorporation of radiolabelled plasma glucose into mammary lactose was used to measure the rate of lactose synthesis in lightly anaesthetized lactating rats. 2. Lactose synthesis showed a diurnal variation with a minimum at 18:00h 3. Food withdrawal for 6h did not affect lactose synthesis in the early morning but greatly decreased it in the afternoon or evening. 4. Plasma glucose, milk sugars and total galactosyltransferase activity (EC 2.4.1.22) did not show the above changes. 5. Measurements of plasma insulin, which varies diurnally, and experiments with injected insulin suggested that variations of insulin within the physiological range do not account for the changes in lactose synthesis described.