High Magnesium and Sirolimus on Rabbit Vascular Cells—An In Vitro Proof of Concept

Drug-eluting bioresorbable scaffolds represent the last frontier in the field of angioplasty and stenting to treat coronary artery disease, one of the leading causes of morbidity and mortality worldwide. In particular, sirolimus-eluting magnesium-based scaffolds were recently introduced in clinical practice. Magnesium alloys are biocompatible and dissolve in body fluids, thus determining high concentrations of magnesium in the local microenvironment. Since magnesium regulates cell growth, we asked whether high levels of magnesium might interfere with the antiproliferative action of sirolimus. We performed in vitro experiments on rabbit coronary artery endothelial and smooth muscle cells (rCAEC and rSMC, respectively). The cells were treated with sirolimus in the presence of different concentrations of extracellular magnesium. Sirolimus inhibits rCAEC proliferation only in physiological concentrations of magnesium, while high concentrations prevent this effect. On the contrary, high extracellular magnesium does not rescue rSMC growth arrest by sirolimus and accentuates the inhibitory effect of the drug on cell migration. Importantly, sirolimus and magnesium do not impair rSMC response to nitric oxide. If translated into a clinical setting, these results suggest that, in the presence of sirolimus, local increases of magnesium concentration maintain normal endothelial proliferative capacity and function without affecting rSMC growth inhibition and response to vasodilators.     

Gastroesophageal pH step-up inaccurately locates proximal border of lower esophageal sphincter

Limiting the widespread use of 24-hr pH monitoring is the necessity of manometrically placing the pH probe 5 cm above the proximal lower esophageal sphincter (LES) border. Therefore, we prospectively compared LES localization by gastroesophageal pH step-up with manometry in 71 patients and 14 asymptomatic volunteers. The gastroesophageal pH step-up significantly correlated with the proximal LES border in patients (r=0.53, P<0.0001) and volunteers (r=0.91, P<0.0001). Based on previously published criteria, the pH step-up value was considered acceptably accurate if it was within ±3 cm (6 cm total span) of the manometrically determined proximal LES border. In 58% of patients and 29% of volunteers the pH step-up occurred outside this accuracy range. Esophagitis (P=0.015) and abnormal reflux parameters (P=0.002) were variables contributing to this error. Subsequent analysis found that the pH step-up overestimated the proximal LES border and occurred at the midportion of the sphincter. The pH step-up still inaccurately located the mid LES in 34% of patients. Therefore, manometry should remain the standard for accurate LES localization prior to placing the pH probe.     

Sensitivity and reproducibility of chemical tests for fecal occult blood with an emphasis on false-positive reactions

In 20 healthy volunteers ingesting 5 to 50 ml of⁵¹Cr-red cells, reaction intensities obtained with four chemical methods for fecal occult blood were compared with the “true” blood loss simultaneously determined by radioassay of each stool. Dilute tincture of guaiac reagent was found to have the same sensitivity and high frequency of false-positive reactions as the saturated guaiac reagent, but was more reproducible. Hematest^TM was slightly less sensitive but was poorly reproducible and yielded frequent false-negative as well as false-positive reactions. False-positive reactions by both methods were not eliminated by a meat-free diet; they were increased with guaiac reagents if stools were stored for 3 or more days. A new guaiac method (Hemoccult^TM) was found to be one-fourth as sensitive as the older tests, but was virtually free from false-positive reactions, even on an unrestricted diet and after storage of the stool specimens. It is recommended that the use of Hematest be abandoned and that Hemoccult be used preferentially if future studies confirm that its sensitivity is sufficient to detect most gastrointestinal lesions which are yielding occult blood.     

Lateral spread response monitoring during microvascular decompression for hemifacial spasm

Aim

The aim of the present study was to determine (1) whether successful intraoperative electromyography monitoring for lateral spread response (LSR) is possible with partial neuromuscular blockade (NMB) in subjects undergoing microvascular decompression (MVD) for hemifacial spasm and (2) the adequate level of NMB to achieve that goal.

Material and methods

A total of 61 patients in whom LSR was monitored during MVD were enrolled in the study. Patients were randomly allocated to two groups: group TOF in which the NMB target was maintenance of two train-of-four (TOF) counts and group T1 in which the NMB target was maintenance of a T₁/Tc ratio of 50?% (T₁: first twitch height of TOF and Tc: control twitch height). The adductor pollicis brevis muscle was used to monitor TOF responses. The frequency of successful LSR monitoring, defined as successful baseline establishment and maintenance of LSR until surgical decompression, was compared between the two groups.

Results

Of the 61 patients 2 were excluded from the study so that 30 patients in group TOF and 29 patients in group T1 were analyzed. The success rate of LSR monitoring was clinically acceptable and significantly higher in group T1 than in group TOF, i.e. n?=?15 (50.0?%) in group TOF versus n?=?24 (82.8?%) in group T1 (P?=?0.008), corresponding to a 32.8?% higher success rate in group T1 than group TOF (95?% CI: 13.9–51.7?%). Mean vecuronium infusion dose was smaller and mean TOF count was higher in group T1 than group TOF with a TOF count =?2 (1) in group TOF versus 3 (1) in group T1 (P?=?0.003). Mean sevoflurane and remifentanil infusion doses were not different between groups. There was no incidence of spontaneous movement during microscopy in either group.

Conclusion

Maintenance of partial NMB with a target T₁/Tc ratio of 50?% resulted in a clinically acceptable success rate of LSR monitoring and surgical condition during MVD. Maintenance of partial NMB with a target T₁/Tc ratio of 50?% rather than TOF count of two during LSR monitoring for MVD can therefore be recommended.     

Parathyroid-hormone variance is only marginally explained by a panel of determinants: a cross-sectional study of 909 hip-fracture patients

Several factors affect the levels of parathyroid hormone (PTH) in hip-fracture patients. We hypothesized that a panel of easily assessable determinants could account for both a substantial proportion of PTH variance and the occurrence of secondary hyperparathyroidism. We evaluated 909 of 981 hip-fracture inpatients admitted consecutively to our Rehabilitation division. In each patient we assessed PTH, 25-hydroxyvitamin D, albumin-adjusted total calcium, phosphate, magnesium, and creatinine on a fasting blood sample 21.3 ± 6.1 (mean ± SD) days after fracture occurrence. Glomerular filtration rate (GFR) was estimated by the 4-variable Modification of Diet in Renal Disease Study equation. Functional level was assessed using the Barthel index. On multivariate analysis, six factors (phosphate, albumin-adjusted total calcium, estimated GFR (eGFR), 25-hydroxyvitamin D, age, and magnesium) were significantly associated with PTH levels. Overall, the panel of variables accounted for 23.7 % of PTH variance. Among the 909 patients, 304 (33.4 %) had PTH levels exceeding the normal range. Six factors (phosphate, albumin-adjusted total calcium, eGFR, 25-hydroxyvitamin D, age, and Barthel index scores) were significantly associated with the category of PTH level (either normal or elevated). The model correctly classified 70.4 % of cases. For the optimal cut-off point, sensitivity was 80 % and specificity was 61 %. Data shows that six factors were significantly associated with PTH levels in hip-fracture inpatients. However, the six factors accounted for only 23.7 % of PTH variance and the presence or absence of secondary hyperparathyroidism was correctly categorized in a modest proportion of cases. We conclude that more knowledge is needed on the factors affecting PTH levels after hip fracture.     

Moderate acute exercise (70% VO2 peak) induces TGF‐β, α‐amylase and IgA in saliva during recovery

Strenuous exercise promotes changes in salivary IgA and can be associated with a high incidence of upper respiratory tract Infections. However, moderate exercise enhances immune function. The effect of exercise on salivary IgA has been well studied, but its effect on other immunological parameters is poorly studied. Thus, this study determined the effect of moderate acute exercise on immunological salivary parameters, such as the levels of cytokines (TGF‐β and IL‐5), IgA, α‐amylase and total protein, over 24 h. Ten male adult subjects exercised for 60 min at an intensity of 70% VO₂ peak. Saliva samples were collected before (‘basal’) and 0, 12 and 24 h after an exercise session. The total salivary protein was lower after 12 and 24 h than immediately after exercise, whereas α‐amylase increased at 12 and 24 h after exercise compared with basal levels. The IgA concentration was increased at 24 h after exercise relative to immediately after exercise, and there was no difference in the IL‐5 while TGF‐β concentration increased in recovery. In conclusion, 70% VO₂ peak exercise does not induce changes immediately after exercise, but after 24 h, it produces an increase in salivary TGF‐β without changing IL‐5.