Vitamin D and disease severity in bronchiectasis.

BACKGROUND: Bronchiectasis is a complex respiratory disease characterised by permanent dilatation of bronchi. Vitamin D plays a role in infective disease by modulating the inflammation. Patients affected by bronchiectasis are frequently Vitamin D deficient and it correlates with lung function decline. We want to understand if there is a correlation between Vitamin D and clinical and radiological severity of bronchiectasis. METHODS: We included 57 patients (17 males/40 female with mean age 60 ±â€¯12 years) between October 2017 and March 2018. We excluded patients with cystic fibrosis, traction bronchiectasis and reporting Vitamin D supplementation. Bronchiectasis severity index (BSI) and Bhalla score were calculated, blood inflammatory markers and Vit. D were measured and lung function tests were performed. RESULTS: Vitamin D is deficient in 64% of patients, sufficient in 36% and normal in 7%. Mean BSI is 7.5 ±â€¯5 and mean Bhalla score is 16 ±â€¯4. Vitamin D levels correlate with Bhalla score (R2 = 0.68, p < 0.001) and BSI (R2 = 0.58, p < 0.0001). The correlation appears to be stronger than other markers of inflammation such as ESR and CRP [R2 = 0.33, p = 0.001 and R2 = 0.39, p = 0.001 respectively]. CONCLUSIONS: We consider Vitamin D as a good predictor of clinical and radiological severity of bronchiectasis.

Blood flow-metabolism imaging with positron emission tomography in patients with diabetes mellitus for the assessment of reversible left ventricular contractile dysfunction.

OBJECTIVES: The purpose of this study was to evaluate the predictive accuracy of positron emission tomography (PET) blood flow-F-18 fluorodeoxyglucose (FDG) imaging in coronary artery disease (CAD) patients with diabetes mellitus (DM). BACKGROUND: Positron emission tomography accurately predicts the postrevascularization improvement in left ventricular dysfunction in unselected patients with CAD. In diabetic patients, however, poor myocardial glucose utilization may limit the accuracy of the approach. METHODS: Forty patients (64+/-10 years old; 19 with DM = group I; 21 without DM = group II) with reduced left ventricular ejection fraction (LVEF = 29+/-6%) were studied with N-13 ammonia and FDG PET before coronary revascularization. Studies were performed after intravenous injection of regular insulin (group I) or oral glucose administration (group II). Blood flow-FDG mismatches and matches were identified by polar map analysis in the three vascular territories of the left anterior descending, left circumflex and right coronary artery. Wall motion and LVEF were assessed by two-dimensional echocardiography before and 158+/-123 days after revascularization. RESULTS: Of 107 vascular territories analyzed, 46 were classified as mismatch, 29 as match and 32 as normal. The FDG image quality, assessed by F-18 myocardium to blood pool activity ratios, and the predictive accuracy were similar in both groups; presence of a blood flow/FDG mismatch had a sensitivity of 92% (group I) and 94% (group II) and a specificity of 85% (group I) and 79% (group II) for an improvement in regional left ventricular function. A postrevascularization improvement in global left ventricular function was related to the extent of blood flow/FDG mismatch; LVEF increased from 30+/-7% to 35+/-7% (p = 0.017) in patients with one mismatch and from 27+/-4% to 41+/-7% (p < 0.001) in those with two mismatches. CONCLUSIONS: The predictive accuracy of blood flow/FDG imaging is maintained in patients with DM when a clinically acceptable study protocol, which guarantees good FDG image quality, is used. The extent of a blood flow/metabolism mismatch is correlated with the magnitude of the postrevascularization improvement in global left ventricular function.

Effect of mental stress on myocardial blood flow and vasomotion in patients with coronary artery disease.

UNLABELLED: In patients with coronary artery disease (CAD), mental stress may provoke ischemic electrocardiograph changes and abnormalities in regional and global left ventricular function. However, little is known about the underlying myocardial blood flow response (MBF) in these patients. METHODS: We investigated the hemodynamic, neurohumoral, and myocardial blood flow responses to mental stress in 17 patients with CAD and 17 healthy volunteers of similar age. Mental stress was induced by asking individuals to solve mathematic subtractions in a progressively challenging sequence; MBF was quantified at rest and during mental stress using 13N ammonia PET. RESULTS: Mental stress induced significant (P < 0.01) and comparable increases in rate-pressure product, measured in beats per minute x mm Hg, in both patients (from 7826 +/- 2006 to 10586 +/- 2800) and healthy volunteers (from 8227 +/- 1272 to 10618 +/- 2468). Comparable increases also occurred in serum epinephrine (58% in patients versus 52% in healthy volunteers) and norepinephrine (22% in patients versus 27% in healthy volunteers). Although MBF increased in patients (from 0.67 +/- 0.15 to 0.77 +/- 0.18 mL/min/g, P < 0.05) and healthy volunteers (from 0.73 +/- 0.13 to 0.95 +/- 0.22 mL/min/g, P < 0.001), the magnitude of flow increase was smaller in patients (14% +/- 17%) than in healthy volunteers (29% +/- 14%) (P = 0.01). The increase in MBF during mental stress correlated significantly with changes in cardiac work in healthy volunteers (r = 0.77; P < 0.001) but not in patients. CONCLUSION: Despite similar increases in cardiac work and comparable sympathetic stimulation in CAD patients and healthy volunteers, CAD patients exhibit an attenuated blood flow response to mental stress that may contribute to mental stress-induced ischemic episodes in daily life.

Coronary vasodilatory capacity and flow reserve in normal myocardium supplied by bypass grafts late after surgery.

Coronary artery bypass surgery is used widely for treating myocardial ischemia. However, blood flow and flow reserve of normally perfused myocardium subtended by bypass grafts have not been evaluated late after surgery. Also, it is unknown whether pharmacologic vasodilation evokes comparable myocardial flow responses in arterial and venous conduits. Myocardial blood flow was quantified at rest and during dipyridamole hyperemia using N-13 ammonia and positron emission tomography (PET) in 15 patients 9 +/- 3 years after bypass surgery and in 10 healthy volunteers. Blood flow was analyzed in 26 territories subtended by bypass grafts with normal wall motion and normal perfusion. Myocardial blood flow at rest did not differ between patients and controls (0.65 +/- 0.14 vs 0.68 +/- 0.16 ml/ g/min) and was similar in normal myocardium subtended by saphenous vein (n = 16) and internal mammary artery grafts (n = 10; 0.64 +/- 0.13 vs 0.66 +/- 0.15 ml/g/min). However, the hyperemic response in normal myocardium supplied by bypass grafts was less than that in controls (1.61 +/- 0.33 vs 2.04 +/- 0.30 ml/g/min, p <0.005). No differences between territories supplied by venous and arterial conduits were observed (1.61 +/- 0.35 vs 1.63 +/- 0.32 ml/g/min). Normal myocardium subtended by bypass grafts exhibited a lower flow reserve than that in controls (2.54 +/- 0.51 vs 3.16 +/- 0.85, p <0.02). Myocardial flow reserve was almost identical in regions supplied by venous and arterial grafts (2.55 +/- 0.48 vs 2.52 +/- 0.58). The similar reduction in vasodilatory capacity together with the normal PET polar map findings during dipyridamole argue against flow limiting stenoses in both venous and arterial bypass conduits late after revascularization. Rather, nonobstructive proliferative fibrointimal changes of the bypass conduits or atherosclerosis of the native resistance vessels might account for this finding.

[Use of Gated-SPECT with with 99mTC-MIBI in the evaluation of the prognostic significance of ventricular arrhythmias during a stress test]. / Empleo del GATED-SPECT con MIBI-Tc99m en la estimación del significado pronóstico de las arritmias ventriculares durante la prueba de esfuerzo.

UNLABELLED: The presence of ventricular complex cardiac arrhythmias in coronary patients, both at rest or during physical exercise, is considered a risk factor for future coronary events or sudden death during long time follow up. The meaning of ventricular complex arrhythmias (VCA) in patients with normal ventricular function and without myocardium ischemia has still not been explained. This study aimed to evaluate if patients with normal ventricular function and no evidence of cardiac ischemia (determined by means of Gated SPECT) who developed VCA during stress test show an increase in cardiac events on later monitoring. PATIENTS AND METHODS: All patients were studied by means of an ergometric exercise test using a standard Bruce protocol and Gated SPECT with Methoxyisobutyl Isonitrile-99mTechnetium (99mTC-MIBI). Sixty-seven (67) patients with normal ventricular function and no evidence of cardiac ischemia were included. RESULTS: 13 patients had VCA and 54 had no ventricular arrhythmias during stress test. During the follow up of 681.3 +/- 469 days, none of the 13 patients had sudden death, angina pectoris or myocardium infarction. CONCLUSIONS: In our sample, the appearance of VCA during stress test in patients without myocardium ischemia and normal ventricular function was not associated with an increase of cardiac events during the monitoring which was carried out.

Noninvasive assessment of coronary microvascular function in women at risk for ischaemic heart disease.

The primary objective of the current review is to describe the assessment of coronary microvascular function by noninvasive imaging techniques in women at risk for and with ischaemic heart disease (IHD). The search criteria were the analyses of the related bibliography published in PUBMED database. Normal or minimal obstructive coronary artery disease (CAD) at angiography is a common finding in women with signs of ischaemia. Up to 50% of them will have coronary microvascular dysfunction, suggesting that the mechanism of ischaemia may be localised at coronary microcirculation level. Noninvasive measurements of coronary microvascular function can be performed by radionuclide techniques. In particular, positron emission tomography (PET) measures myocardial blood flow (MBF) not only relatively but also in absolute units. Thus, PET offers the possibility to uncover microvascular dysfunction even in patients without obstructive CAD. PET-derived estimates of MBF showed an abnormal coronary microvascular function in women with chest pain and non-obstructive CAD and in women with high-risk conditions for CAD. Interestingly, there is a relationship between an abnormal coronary vascular function and adverse cardiovascular outcomes. In particular, this significant relationship was observed with measurements related to endothelial function. Recent evidence suggests that vascular dysfunction plays a central role as an estimator of outcomes in women at risk for or with IHD. Therefore, assessment of coronary vascular function in these women appears to be of clinical relevance. Whether such evaluation may have an impact to reduce cardiac events needs further investigation.

Converting enzyme inhibition and renal function of conscious uninephrectomized rats [correction of enzyme].

We studied the effect of a Converting Enzyme Inhibitor, Captopril, on renal function of conscious, chronically instrumented uninephrectomized rats three weeks after surgery and normal two kidney rats. Captopril increased glomerular filtration rate from 9.28 +/- 0.50 to 14.23 +/- 1.07 ml/min.kg and effective renal plasma flow from 31.6 +/- 2.4 to 45.8 +/- 3.7 ml/min.kg in two kidney rats. Glomerular filtration rate and effective renal plasma flow of uninephrectomized rats did not change after acute converting enzyme inhibition (from 6.96 +/- 0.61 to 7.16 +/- 0.39 and 24.5 +/- 2.2 to 27.9 +/- 1.5 ml/min.kg respectively). Plasma renin activity was lower in uninephrectomized rats (0.72 +/- 0.15 ng AngI/ml.h) than in intact rats (1.41 +/- 0.20 ng AngI/ml.h). Acute converting enzyme inhibition increased urinary sodium excretion, fractional sodium excretion and plasma renin activity in both, two kidney and uninephrectomized rats without changes of mean arterial pressure. Present data suggest that the Angiotensin II does not participate in the control of glomerular filtration rate and effective renal plasma flow of uninephrectomized rats but it is implicated in the control of Na homeostasis.

The use of remifentanil for bloodless surgical field during vertebral disc resection.

BACKGROUND: A short hospital stay is nowadays desirable and affordable for a wide range of surgical pathology, respecting safety of care and home discharge. In the present study, the Authors investigated the use of TIVA with propofol/remifentanil during microsurgical vertebral disc resection to maintain a controlled vascular hypotension for bloodless surgical field aiming to reduce the operating time and consequently recovery room length of stay and morbility related to anaesthesia. METHODS: The study took place in a 300 bed Orthopaedics hospital over a period of 3 months and 50 ASA I-II patients were enrolled in this trial; further data are presented for comparison of 50 ASA I-II patients homogeneous for age and sex to the studied population, operated under a standard TIVA with propofol and boluses of fentanyl. Duration of anaesthesia and surgery, time for awakening after cessation of TIVA, incidence of postoperative nausea and vomiting (PONV), amount and quality of postoperative analgesia, length of stay in the recovery room are reported in statistical presentation. RESULTS: Time of surgery and anaesthesia were reduced in the remifentanil group compared with the fentanyl group, thanks to an easily reachable and durable state of controlled hypotension in the first group without the use of any other drug. The recovery profile was shorter in the remifentanil group the drug being rapidly metabolised by plasma cholinesterase. CONCLUSIONS: No difference occurred between the two groups regarding quality and amount of postoperative analgesia, while PONV presented more in the fentanyl group and shivering more in the remifentanil group.

L-Arginine normalizes coronary vasomotion in long-term smokers.

BACKGROUND: Noninvasive measurements of myocardial blood flow (MBF) with PET revealed an abnormal coronary vasomotor response to cold pressor test in healthy long-term smokers. If coronary endothelial dysfunction accounted for this abnormality, we hypothesized that it could be reversed by L-arginine as the substrate for NO synthase. METHODS AND RESULTS: MBF was quantified with 13N-labeled ammonia and PET in 11 healthy smokers (age, 45+/-10 years; 27+/-10 years of smoking) and in 12 age-matched nonsmokers on 2 separate days. On day 1, MBF was measured at rest and, after intravenous L-arginine, during cold pressor test. On day 2, MBF was measured during cold pressor test and then at rest during L-arginine. Baseline rate-pressure product (RPP) (6559+/-1590 versus 7144+/-1157 bpmxmm Hg) and MBF (0.65+/-0.14 versus 0.73+/-0.13 mL x g-1 x min-1) were similar in nonsmokers and smokers. Cold pressor test increased RPP similarly in both groups (53+/-26% versus 46+/-26%), whereas MBF increased in nonsmokers (to 0.93+/-0.25 mL x g-1 x min-1; P<0.05) but not in smokers (0.80+/-0.16 mL x g-1 x min-1). The percent MBF increase differed between nonsmokers and smokers (44+/-25% versus 11+/-14%; P=0.0017). However, after L-arginine, the magnitude of MBF response to cold pressor test no longer differed between groups (48+/-36% versus 48+/-28%), whereas RPP again increased similarly in the 2 groups (59+/-30% versus 44+/-16%). L-Arginine had no effect on resting MBF in smokers or nonsmokers. CONCLUSIONS: Our findings implicate the coronary endothelium as the major site of the abnormal vasomotor response in long-term smokers. Cold pressor test combined with PET imaging may allow the noninvasive identification of coronary endothelial dysfunction in humans.

Effects of long-term smoking on myocardial blood flow, coronary vasomotion, and vasodilator capacity.

BACKGROUND: The effect of long-term smoking on coronary vasomotion and vasodilator capacity in healthy smokers is unknown. METHODS AND RESULTS: Myocardial blood flow (MBF) was quantified with [13N]ammonia and positron emission tomography (PET) at rest, during cold pressor testing (endothelium-dependent vasomotion), and during dipyridamole-induced hyperemia in 16 long-term smokers and 17 nonsmokers. MBF at rest did not differ between the 2 groups. Cold induced similar increases in rate-pressure product (RPP) in smokers and nonsmokers. However, MBF increased only in nonsmokers and was, during cold, higher than in smokers (0.91+/-0.18 versus 0.78+/-0.14 mL x g(-1) x min(-1), P<0.05). MBF normalized to the RPP (derived from the ratio of MBF ([milliliters per gram per minute] to RPP [beats per minute times millimeters of mercury] times 10000) declined in smokers but remained unchanged in nonsmokers (0.86+/-0.10 versus 0.72+/-0.11, P=0.0006, and 0.99+/-0.25 versus 0.96+/-0.27, P=NS). The hyperemic response to dipyridamole and the myocardial flow reserve did not differ between the 2 groups. In a multiple regression model adjusted for age, sex, serum lipid levels, years of smoking, and pack-years, years of smoking was the strongest predictor of the normalized blood flow response to cold (P<0.001), followed by the HDL/LDL ratio. CONCLUSIONS: The normal hyperemic response to dipyridamole in long-term smokers indicates a preserved endothelium-independent coronary vascular smooth muscle relaxation, whereas the abnormal response to cold suggests a defect in coronary vasomotion likely located at the level of the coronary endothelium. Its severity depends on the total exposure time to smoking.

Insulin receptors and insulin sensitivity in normo and hyperinsulinemic obese patients.

The authors have studied insulin receptors on peripheral blood monocytes and insulin sensitivity, evaluated by simultaneous infusion of glucose, insulin and somatostatin in 10 control subjects and in 20 obese patients with normal glucose tolerance. The obese patients have been divided into two groups, normo (NO) and hyperinsulinemic (HO), according to the total insulin response during OGTT. We considered HO patients with insulin response higher than M + 2DS of controls. Obese patients showed, in comparison to the controls, a lower specific binding and higher degree of insulin resistance. The subdivision of obese patients allowed us to distinguish two groups. The first was characterized by basal hyperinsulinemia, normal insulin response to the stimulus, reduced number of insulin receptors and normal or slightly reduced sensitivity. The second group showed high basal and after stimulus insulinemic values, reduced number of insulin receptors and high level of insulin resistance. When we compared the two groups of obeses we found that the first has a shorter duration of obesity and lower blood glucose values after OGTT. However both groups show the same reduction of insulin bound and the same degree of basal hyperinsulinemia. These data suggest that a reduction of insulin receptors is not the main factor responsible for insulin resistance in obesity. Furthermore, the presence of basal hyperinsulinemia and normal insulin sensitivity in our first group suggests that the modification of basal insulin concentrations is not dependent on the presence of insulin resistance.

Regulation of myocardial blood flow response to mental stress in healthy individuals.

Mental stress testing has been proposed as a noninvasive tool to evaluate endothelium-dependent coronary vasomotion. In patients with coronary artery disease, mental stress can induce myocardial ischemia. However, even the determinants of the physiological myocardial blood flow (MBF) response to mental stress are poorly understood. Twenty-four individuals (12 males/12 females, mean age 49 +/- 13 yr, range 31-74 yr) with a low likelihood for coronary artery disease were studied. Serum catecholamines, cardiac work, and MBF (measured quantitatively with N-13 ammonia and positron emission tomography) were assessed. During mental stress (arithmetic calculation) MBF increased significantly from 0.70 +/- 0.14 to 0.92 +/- 0.21 ml x min(-1) x g(-1) (P < 0.01). Mental stress caused significant increases (P < 0.01) in serum epinephrine (26 +/- 16 vs. 42 +/- 17 pg/ml), norepinephrine (272 +/- 139 vs. 322 +/- 136 pg/ml), and cardiac work [rate-pressure product (RPP) 8,011 +/- 1,884 vs. 10,416 +/- 2,711]. Stress-induced changes in cardiac work were correlated with changes in MBF (r = 0.72; P < 0.01). Multiple-regression analysis revealed stress-induced changes in the RPP as the only significant (P = 0.0001) predictor for the magnitude of mental stress-induced increases in MBF in healthy individuals. Data from this group of healthy individuals should prove useful to investigate coronary vasomotion in individuals at risk for or with documented coronary artery disease.

Glucose tolerance and insulin secretion in pregnancy.

The authors have studied the behaviour of plasma glucose, insulinaemia and insulin-glucose ratio in 2 groups of pregnant women with BMI values > or = or <26, respectively. Each group was divided into 3 subgroups on the basis of an oral glucose tolerance test (OGTT) response: GIGT (gestational impaired glucose tolerance), GD (gestational diabetes), and C (normal controls). Data from non-obese pregnant women demonstrate that both basal and OGTT-stimulated glucose levels were significantly different in all subgroups. The total insulin amount in the GIGT and GD subgroups is quite similar to or greater than the controls, but with a significant reduction of the insulin-glucose ratio. In GD also an absolute deficiency of insulin rise at 30 min during the glucose load, as in subjects with Type 2 diabetes mellitus (T2DM), was observed. The behaviour of these parameters in obese pregnant women seems to be similar, even though with some significant differences: in these subjects, there is a less clear-cut differentiation among all subgroups, and the appearance of gestational diabetes is not accompanied by a significant decrease of insulin secretion at 30 min. Our data seem to demonstrate that insulin resistance with an inadequate hyperinsulinaemia is a common factor for the alterations of carbohydrate metabolism during pregnancy. Only in the non-obese patients with gestational diabetes, is there an absolute defect of early insulin response to the glucose load, as it is seen in T2DM.