Left ventricular dysfunction and intra-ventricular dyssynchrony in idiopathic pulmonary arterial hypertension.

BACKGROUND: Left ventricular (LV) filling pressures are normal in idiopathic pulmonary arterial hypertension (IPAH). However, direct and indirect interactions between the RV and LV can affect LV performance. We explored LV strain and LV intra-ventricular dyssynchrony in IPAH using feature tracking CMR (CMR-FT). METHODS: Seventy IPAH patients and 40 healthy volunteers were included. Patients underwent CMR and right heart catheterisation. The 4-chamber cine was used to calculate LV longitudinal strain (EllLV). LV circumferential (EccLV) and radial strain (ErrLV) were derived from a short axis cine. LV longitudinal, circumferential and radial intra-ventricular dyssynchrony indices were calculated. RESULTS: There were no differences between the IPAH and healthy volunteer group in LV ejection fraction (66.1% vs 64.2% p = 0.6672). EccLV (-29.1 vs -32.1 p = 0.0323) and EllLV (-16.6 vs -23.7 p < 0.0001) were lower in IPAH. In patients with more severe disease, there was greater impairment of ErrLV compared to mild disease (50.9 vs 87.5 P < 0.0001). LV synchrony was impaired in all directions in IPAH. ErrLV was associated with RV ejection fraction (r = 0.66), RV end-systolic volume index (r = -0.59), pulmonary vascular resistance (PVR)(r = 0.51) and stroke volume index (SVI)(r = 0.44). In a multivariate model with age, SVI and PVR, ErrLV (HR 0.970 p = 002) and radial dyssynchrony (HR 3.759 p < 0.0001) independently predicted survival. CONCLUSION: In IPAH, LV is dyssynchronous with impaired function. Measures of LV strain and intraventricular synchrony were associated with known markers of disease severity. These LV variables which are likely to be related to ventricular interaction, may add incremental value to known prognostic variables in IPAH.

The relationship between adiposity, bone density and microarchitecture is maintained in young women irrespective of diabetes status.

BACKGROUND: The relationship between bone health and adiposity and how it may be affected in people with chronic metabolic conditions is complex. METHODS: Seventeen women with type 1 diabetes mellitus (T1DM) and nine age-matched healthy women with a median age of 22.6 years (range, 17.4, 23.8) were studied by 3T MRI and MR spectroscopy to assess abdominal adiposity, tibial bone microarchitecture and vertebral bone marrow adiposity (BMA). Additional measures included DXA-based assessments of total body (TB), femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD) and fat mass (FM). RESULTS: Although women with T1DM had similar BMI and BMA to the controls, they had higher visceral and subcutaneous adiposity on MRI (P<.05) and total body FM by DXA (P=.03). Overall, in the whole cohort, a clear inverse association was evident between BMA and BMD at all sites (P<.05). These associations remained significant after adjusting for age, BMI, FM and abdominal adiposity. In addition, visceral adiposity, but not subcutaneous adiposity, showed a positive association with BMA (r, .4, P=.03), and a negative association with total body BMD (r, .5, P=.02). Apparent trabecular separation as assessed by MRI showed an inverse association to total body BMD by DXA (r, -.4, P=.04). CONCLUSION: Irrespective of the presence of an underlying metabolic condition, young women display a negative relationship between MRI-measured BMA and DXA-based assessment of BMD. Furthermore, an association between BMA and visceral adiposity supports the notion of a common origin of these two fat depots.

MRI-based abnormalities in young adults at risk of adverse bone health due to childhood-onset metabolic & endocrine conditions.

OBJECTIVE: Traditional methods of bone densitometry may not provide a comprehensive assessment of bone health. We aimed to assess bone micro-architecture and bone marrow adiposity (BMA) by MRI in adults with osteogenesis imperfecta (OI) and endocrinopathy including GH deficiency and/or hypogonadism. MEASUREMENTS: High-resolution micro-MRI images were acquired at the tibia using 3T MRI to calculate parameters of bone micro-architecture in seven adults with OI and 10 adults with endocrinopathies. MR Spectroscopy was performed in participants to calculate vertebral BMA, which was expressed as percentage fat fraction (%FF). Lumbar spine DXA was performed to assess bone mineral density. The MRI data were compared with a group of 22 healthy adults who were divided into two age-matched control groups. RESULTS: Intra-operator repeatability was high, with an average CoV of 1% for micro-MRI and 2·5% for MRS. The ratio of apparent bone volume to total volume (appBV/TV) in the endocrinopathy and OI groups was lower than in age-matched control groups (P = 0·003 and P = 0·008 respectively). A weak association between DXA BMD and appBV/TV was also observed (r = 0·5, P = 0·045). %FF was higher in the endocrinopathy group than in the age-matched control group (P = 0·005), but no difference in %FF was observed between the OI group and their age-matched control group (P = 0·26). CONCLUSIONS: MRI provides valuable detailed information on the micro-architecture and adiposity of bones and is capable of showing clear differences in bone parameters in a range of clinical conditions associated with abnormal bone health.

Acute phase proteins in bovine milk in an experimental model of Staphylococcus aureus subclinical mastitis.

The objectives were to establish the origin of 2 acute phase proteins in milk during subclinical bovine mastitis and to characterize the relationship between those proteins in milk and blood. Haptoglobin (Hp) and mammary-associated serum amyloid A (M-SAA3) appear in milk during mastitis, whereas Hp and serum amyloid A increase in serum during mastitis. The concentrations of these proteins were determined in an experimental model using a field strain of Staphylococcus aureus to induce subclinical mastitis in dairy cows. The expression of mRNA coding for these proteins was assessed and the presence of M-SAA3 in mammary tissues was determined using immunocytochemistry. Increases of M-SAA3 and Hp in milk occurred within 12 h of Staphylococcus aureus infusion, with peak concentrations occurring 3 d after infusion of the bacteria. The increase of acute phase proteins in milk (15 h) preceded the increase in serum concentrations of both proteins (24 h). Expression of mRNA for M-SAA3 and Hp increased in both mammary and hepatic tissues 48 h after infusion of the mammary glands. In mammary tissue, the increase of M-SAA3 mRNA was greater than the increase in Hp mRNA expression, whereas in hepatic tissue, the increase in M-SAA3 mRNA was less than that for Hp mRNA. Immunocytochemistry demonstrated that M-SAA3 protein was present within secretory epithelial cells at significantly higher levels in infected mammary glands than in control tissues. These proteins, which have host defense and antibacterial activities, may play a significant role in the early response to invasion of mammary tissues by pathogenic bacteria.

A psychometric experiment in causal inference to estimate evidential weights used by epidemiologists.

A psychometric experiment in causal inference was performed on 159 Australian and New Zealand epidemiologists. Subjects each decided whether to attribute causality to 12 summaries of evidence concerning a disease and a chemical exposure. The 1,748 unique summaries embodied predetermined distributions of 19 characteristics generated by computerized evidence simulation. Effects of characteristics of evidence on causal attribution were estimated from logistic regression, and interactions were identified from a regression tree analysis. Factors with the strongest influence on the odds of causal attribution were statistical significance (odds ratio = 4.5 if 0.001 < or = P < 0.05 and 7.2 if P < 0.001, vs P > or = 0.05); refutation of alternative explanations (odds ratio = 8.1 for no known confounder vs none adjusted); strength of association (odds ratio = 2.0 if 1.5 < relative risk < or = 2.0 and 3.6 if relative risk > 2.0, vs relative risk < or = 1.5); and adjunct information concerning biological, factual, and theoretical coherence. The refutation of confounding reduced the cutpoint in the regression tree for decision-making based on strength of association. The effect of the number of supportive studies reached saturation after it exceeded 12 studies. There was evidence of flawed logic in the responses concerning specificity of effects of exposure and a tendency to discount evidence if the P-value was a "near miss" (0.050 < P < 0.065). Evidential weights based on regression coefficients for causal criteria can be applied to actual scientific evidence.

Cytokines and the acute phase response in post-treatment reactive encephalopathy of Trypanosoma brucei brucei infected mice.

Stimulation of the acute phase response during infection of mice with Trypanosoma brucei brucei (T. b. brucei) was investigated in an experimental model of the post-treatment reactive encephalopathy (PTRE), a common side-effect of anti-trypanosome therapy. Plasma levels of the acute phase proteins (APP), haptoglobin (Hp) and serum amyloid P (SAP) increased by day 7 post-infection, but by day 20 had fallen to an intermediate level. This was accompanied by induction of the cytokines, interleukin (IL)-6 and tumour necrosis factor-alpha (TNFalpha) in both liver and brain. Treatment of mice on day 21 with a subcurative dose of diminazene aceturate (Berenil), a procedure known to induce a mild PTRE, cleared the parasite from the circulation with plasma APP and liver expression of mRNA for IL-6 and TNFalpha returning to the levels in the controls. Cytokine mRNA for both IL-6 and TNFalpha was detected in the brains of animals with developing PTRE although TNFalpha was not significantly greater than in the control group. A further subcurative dose of Berenil, leading to a more severe PTRE, was associated with elevated serum concentrations of Hp and SAP, increased TNFalpha mRNA in the liver and detectable IL-6 and TNFalpha mRNA in the brain. mRNA for IL-1alpha was expressed in brain and liver samples from all animals. A severe PTRE caused a systemic acute phase response which was not apparent with a mild PTRE. The pattern of cytokine mRNA induction was similar following both drug treatments. However, the difference in APP production could be caused by a breakdown in the blood-brain barrier during severe PTRE allowing cytokine synthesised in the brain to enter the circulation and maintain a systemic response.

Acute phase proteins in serum and milk from dairy cows with clinical mastitis.

The serum concentrations of haptoglobin, serum amyloid A and alpha1 acid glycoprotein were determined in serum collected from healthy dairy cows and cows with clinical mastitis, graded as mild (clots in milk) or moderate (clots in milk and visible signs of inflammation in the mammary gland/s) to assess their relative diagnostic value in detecting the disease. The concentrations of haptoglobin and serum amyloid A were also measured in milk collected from infected and uninfected quarters. The concentrations of haptoglobin and serum amyloid A were higher in the serum and milk from the cows with mild or moderate mastitis. The diagnostic value of haptoglobin in differentiating between healthy animals and those with mastitis gave sensitivities and specificities of 82 per cent and 94 per cent respectively with serum and 86 per cent and 100 per cent with milk. The diagnostic value of serum amyloid A in differentiating between healthy animals and those with mastitis gave sensitivities and specificities of 83 per cent and 90 per cent with serum and 93 per cent and 100 per cent with milk. The diagnostic value of serum alpha1 acid glycoprotein in differentiating between healthy animals and those with mastitis gave sensitivities and specificities of 62 per cent and 91 per cent.

The acute phase response of acid soluble glycoprotein, alpha(1)-acid glycoprotein, ceruloplasmin, haptoglobin and C-reactive protein, in the pig.

The acute phase serum protein response to infection, inflammation or trauma has been identified in a number of species and consists of alterations to the serum concentrations of several proteins. It is known that the profile of acute phase protein response to stimulation differs between species. In the pig, individual proteins have been identified as acute phase proteins in association with infection or pathological lesions. In this investigation, turpentine injection was used to stimulate a sterile inflammatory lesion in pigs so that the relative changes in acute phase protein could be determined and the most appropriate proteins identified as markers of inflammation. The mean serum concentration of the acid soluble glycoprotein fraction showed a two-fold increase with a peak 2 days after treatment. The mean serum alpha(1)-acid glycoprotein concentration fluctuated during the period following injection of turpentine with little difference from the control animals. The mean concentration of serum ceruloplasmin increased by 40% by the 4th day following treatment. The mean serum concentration of haptoglobin increased more than two-fold reaching a peak on the 2nd day after treatment. The mean serum C-reactive protein level increased eight-fold with a peak on the 2nd day after turpentine injection. C-reactive protein and haptoglobin are likely to be the best markers for the identification of inflammatory lesions in pigs.

The adjuvanticity of Algammulin, a new vaccine adjuvant.

Algammulin is a suspension of 1-2 microns ovoids of the immune stimulant gamma inulin (g-IN) in which alum is embedded as a carrier for protein or other anionic antigens. Tests for specific IgG and seroconversion responses in mice immunized with keyhole limpet haemocyanin (KLH) show that the presence of g-IN on the alum has increased its adjuvanticity 6- to 17-fold (p less than 0.001), and thus has a synergistic effect. A mixture of alum and g-IN was no more active than alum alone. Low KLH doses at borderline seroconversion levels (0.1-1 microgram/mouse) allow comparison with a vaccine situation. The improved Algammulin responses extended to 58 days after primary doses and to memory recall after boost at 65 days. At 1 mg Algammulin i.p. in primary and secondary doses the anti-KLH IgG responses were equal to those from Freund's complete adjuvant. The g-IN on the alum increased all responses tested (IgG 1, 2a, 2b, 3 and total IgG, IgM, IgA and IgE), but changed the emphasis from that of alum (favouring mostly IgG 2a, IgG 2b and IgA).

Bubbling humidifiers produce microaerosols which can carry bacteria.

It is widely held that bubbling humidifiers do not produce microaerosols, although prior studies have resulted in conflicting evidence. We have studied this phenomenon in a clean room using an airborne particle counter and samplers for airborne bacteria. At gas flow rates between 10 and 80 L/min, a Cascade 1 humidifier produced between 460 and 999 water droplets/L humidified gas. Total water volume aerosolized was approximately 10(-8) ml/L humidified gas. Seventy-three percent of the particles had diameters between 1 and 5 microns. With the reservoir containing 6.4 X 10(6) P. aeruginosa/ml, it produced between 2 and 9 P. aeruginosa/L humidified gas. Most of the bacteria were in particles of a size likely to be deposited in the lung. This bacterial carry-over was between 20 and 150 times the amount predicted by multiplication of the water volume aerosolized times the concentration of bacteria in the humidifier reservoir. An Air Life humidifier produced fewer particles which were also of a size likely to be deposited in the lung and, when the reservoir contained P. aeruginosa, it aerosolized bacteria. Wick-type humidifiers did not produce detectable aerosol or bacterial carry-over. Although the clinical significance of these findings has not been established, they provide a rationale for the CDC recommendations for procedures designed to keep bubbling humidifier reservoir water uncontaminated.

Preextubation ventilatory measurements in newborns and infants.

Maximum inspiratory pressure, inspiratory capacity, and minute ventilation were measured in a group of infants prior to extubation to determine whether these parameters predicted successful extubation. Data obtained suggested that maximum inspiratory pressure and inspiratory capacity more accurately assessed the patient's ability to tolerate extubation than minute ventilation, pH, PCO2, or respiratory rate. A maximum inspiratory pressure of greater than 33 torr and an inspiratory capacity of greater than 150 ml/m2 were predictive of successful extubation.