Bolus Application Research Articles

Effectiveness of ceftazidime/avibactam as a continuous infusion in critically ill patients with OXA-48-producing Klebsiella pneumoniae infection

Introduction. Ceftazidime/avibactam, a novel beta-lactam antibiotic, demonstrates time-dependent bacterial killing; thus, new reports advocate its administration as a continuous infusion, as opposed to bolus or prolonged infusion application. Methods. Critically ill COVID-19 patients (n=10) superinfected with OXA-48-producing Klebsiella pneumoniae susceptible to ceftazidime/avibactam were treated with ceftazidime/avibactam as a continuous infusion for an average of 10 days. The treatment regimen included an initial loading dose, followed by a continuous infusion of ceftazidime/avibactam. These patients were immunocompromised because of severe COVID-19, treatment with corticosteroids, and some solid organ transplant recipients (n=2), all with high disease severity scores. Discussion. Considering the published literature to this date, this is the one of first reports describing the real-life results of using a continuous infusion of ceftazidime/avibactam in the treatment of OXA-48-producing K. pneumoniae superinfection in critically ill COVID-19 patients. Microbiological effectiveness of treatment, evidenced by negativization of microbiological samples, was achieved in eight cases (80%) overall, but in patients with sepsis and urinary tract infection, the cure rate was 100%. Conclusion. The reasons for the low treatment success rates in pneumonia caused by OXA-48-producing K. pneumoniae could be explained by the concurrent severe COVID-19 pneumonia.

The Impact of Chronic Oral Beta-Blocker Intake on Intravenous Bolus Landiolol Response in Hospitalized Intensive Care Patients with Sudden-Onset Supraventricular Tachycardia-A Post Hoc Analysis of a Cross-Sectional Trial.

Background: Landiolol, a highly cardioselective agent with a short half-life (2.4-4 min), is commonly used as a perfusor or bolus application to treat tachycardic arrhythmia. Some small studies suggest that prior oral β-blocker use results in a less effective response to intravenous β-blockers. Methods: This study investigated whether prior chronic oral β-blocker (Lβ) or no prior chronic oral β-blocker (L-) intake influences the response to intravenous push-dose Landiolol in intensive care patients with acute tachycardic arrhythmia. Results: The effects in 30 patients (67 [55-72] years) were analyzed, 10 (33.3%) with and 20 (66.7%) without prior oral β-blocker therapy. Arrhythmias were diagnosed as tachycardic atrial fibrillation in 14 patients and regular, non-fluid-dependent, supraventricular tachycardia in 16 cases. Successful heart rate control (Lβ 4 vs. L- 7, p = 1.00) and rhythm control (Lβ 3 vs. L- 6, p = 1.00) did not significantly differ between the two groups. Both groups showed a significant decrease in heart rate when comparing before and after the bolus administration, without significant differences between the two groups (Lβ -26/min vs. L- -33/min, p = 0.528). Oral β-blocker therapy also did not influence the change in mean arterial blood pressure after Landiolol bolus administration (Lβ -5 mmHg vs. L- -4 mmHg, p = 0.761). Conclusions: A prior chronic intake of β-blockers neither affected the effectiveness of push-dose Landiolol in heart rate or rhythm control nor impacted the difference in heart rate or mean arterial blood pressure before and after the Landiolol boli.

The influence of different application patterns of propofol on the sedation courses during drug-induced sleep endoscopy.

The course of sedation during drug-induced sleep endoscopy (DISE) depends on the application pattern of the sedative drug. The depth of sedation should imitate light and deep sleep as well. Moreover, there should be as many breathing cycles as possible available for observation during light and deep sedation. The aim of the study was to evaluate different rates of propofol application with respect to the achieved depth and length of the course of sedation. Sixty-three consecutive patients with obstructive sleep apnea and/or snoring undergoing DISE were randomly sedated by propofol perfusion at seven different application patterns: 14, 16, 18, 19, 20, 22 mg/kg/h (0.233, 0.267, 0.3, 0.317, 0.333, 0.367 mg/kg/min) per perfusor and individual bolus application 10 mg each. Sedation depth was monitored by BiSpectral Index™ (BIS). The influence of baseline parameters and the courses of sedation were analyzed. The application rate was the only factor that influenced the depth of sedation. Basic parameters (gender, age, body mass index, apnea-hypopnea index) had no influence on the depth of sedation. The sedation depth was dependent on the rate of propofol application. Regimes at 14 and 16 mg/kg/h as well as bolus application did not reach BIS levels below 50 representing deep sleep. Propofol doses of more than 20 mg/kg/h led to rapid decreases of sedation levels below deep sleep niveau. Propofol rates between 18 and 20 mg/kg/h enable BIS levels below 50 representing deep sleep and providing enough breathing cycles for observation. Lower application rates of propofol provide slower courses of sedation and shallower depths of sedation. A rate of 14 mg/kg/h might be appropriate to reach a sedation plateau at light sleep. A rate of 18 mg/kg/h leads to a sedation, corresponding to deep sleep. The combination of both rates might be a suitable pattern for performing sedation-controlled DISE. 2: Randomized trial.

The impact of bolus on clinical outcomes for post-mastectomy breast cancer patients treated with IMRT: data from China

PurposeThis study aims to investigate the effects of chest wall bolus in intensity-modulated radiotherapy (IMRT) technology on clinical outcomes for post-mastectomy breast cancer patients.Materials and methodsThis retrospective study included patients with invasive carcinoma ((y)pT0-4, (y)pN0-3) who received photon IMRT after mastectomy at the Affiliated Hospital of Qingdao University from 2014 to 2019. The patients were divided into two groups based on whether they received daily bolus application or not, and the baseline characteristics were matched using propensity score matching (PSM). Cumulative incidence (CI) of local recurrence (LR), locoregional recurrence (LRR), overall survival (OS) and disease-free survival (DFS) were evaluated with a log-rank test. Acute skin toxicity and late radiation pneumonia was analyzed using chi-square test.ResultsA total of 529 patients were included in this study, among whom 254 (48%) patients received bolus application. The median follow-up time was 60 months. After matching, 175 well-paired patients were selected. The adjusted 5-year outcomes (95% confidence interval) in patients treated with and without bolus were, respectively: CI of LR 2.42% (0.04–4.74) versus 2.38% (0.05–4.65), CI of LRR 2.42% (0.04–4.74) versus 3.59% (0.73–6.37), DFS 88.12% (83.35–93.18) versus 84.69% (79.42–90.30), OS 94.21% (90.79–97.76) versus 95.86% (92.91–98.91). No correlation between bolus application and skin toxicity (P = 0.555) and late pneumonia (P = 0.333) was observed.ConclusionsThe study revealed a low recurrence rate using IMRT technology. The daily used 5 mm chest wall bolus was not associated with improved clinical outcomes.

Check valves : Important facts for safe use

Patients benefit from the use of check valves when drugs with a particularly short half-life (e.g., catecholamines) are continually administered through aone-way valve or when an accidental retrograde bolus application must be prevented, as in the event of arapid sequence induction and intubation. The lack of acheck valve can prevent the administered drug from working in the intended manner resulting in potentially insufficient treatment and negative consequences for the patient. In order to ensure the highest level of patient safety while using check valves appropriate training of medical personnel is essential. In contrast, preventable dangers (e.g., infections, awareness) exist when safety measures are disregarded, including the re-use of medications, syringes or disposable materials in successive patients after having only exchanged the check valves. It is not clear how often this is practiced in German-speaking areas.

Superficial Dosimetry Study of the Frequency of Bolus Using in Volumetric Modulated Arc Therapy after Modified Radical Mastectomy.

To investigate the effect of various frequencies of bolus use on the superficial dose of volumetric modulated arc therapy after modified radical mastectomy for breast cancer. Based on the computed tomography images of a female anthropomorphic breast phantom, a 0.5 cm silicone-based 3D-printed bolus was created. Nine points evenly distributed on the breast skin were selected for assessing the skin dose, and a volume of subcutaneous lymphatic drainage of the breast (noted as ROI2-3) was delineated for assessing the chest wall dose. The treatment plans with and without bolus (plan_wb and plan_nb) were separately designed using the prescription of 50 Gy in 25 fractions following the standard dose constraints of the adjacent organ at risk. To characterize the accuracy of treatment planning system (TPS) dose calculations, the doses of the nine points were measured five times by thermoluminescence dosimeters (TLDs) and then were compared with the TPS calculated dose. Compared with Plan_nb (144.46 ± 10.32 cGy), the breast skin dose for plan_wb (208.75 ± 4.55 cGy) was significantly increased (t = -18.56, P < 0.001). The deviation of skin dose was smaller for Plan_wb, and the uniformity was significantly improved. The calculated value of TPS was in good agreement with the measured value of TLD, and the maximum deviation was within 5%. Skin and ROI2-3 doses were significantly increased with increasing frequencies of bolus applications. The mean dose of the breast skin and ROI2-3 for 15 and 23 times bolus applications were 45.33 Gy, 50.88 Gy and 50.36 Gy, 52.39 Gy, respectively. 3D printing bolus can improve the radiation dose and the accuracy of the planned dose. Setting Plan_wb to 15 times for T1-3N+ breast cancer patients and 23 times for T4N+ breast cancer patients can meet the clinical need. Quantitative analysis of the bolus application frequency for different tumor stages can provide a reference for clinical practice.

Comparison of Ultrasound Guided Transversus Abdominis Plane Block versus Intravenous Patient Controlled Analgesia for Post Operative Analgesia in Parturients Undergoing Cesarean Delivery under General Anesthesia

Abstract Background Cesarean delivery rates are rising, and efficient postoperative pain management is a key priority of women undergoing cesarean delivery. Inadequate pain management in the acute postoperative period is associated with persistent pain, greater opioid use, delayed functional recovery, and increased postpartum depression. In addition to pain relief, optimal management of patients after cesarean delivery should address the goals of unrestricted maternal mobility, minimal maternal and neonatal side effects, rapid recovery to baseline functionality, and early discharge home. Aim of the Work The Primary aim is to compare the efficacy of TAP block versus PCA with IV morphine to Provide Prolonged Post-operative analgesia. Secondary objective is to identify the side effects of both techniques as post operative analgesia. Patients and Methods 74 patients were randomly allocated to one of 2 groups (n=37; each); group A received general anesthesia followed by US-guided TAB block at the end of the operation before extubation using 20 ml bupivacaine 0.25% bilaterally. Group B: received general anesthesia followed by PCA at the end of operation after extubation via dedicated 20 G canula woth disposable PCA pump of 100 ml volume, through continuous infusion of 2 ml/hr &amp; bolus application of 1 ml with 15 min lock time using 50 mg morphine, 60 mg ketorolac, 2 mg granisetrone &amp; filled with 0.9% normal saline. Conclusion when TAP block is given in the volume of 20 mL bilaterally, it is as effective as intravenous Morphine PCA in pain treatment. Compared with intravenous PCA, TAP block can be considered as a more preferable method because it can avoid the systemic actions of morphine used for PCA, and its analgesic effect begins earlier.

Clinical Application of a Customized 3D-Printed Bolus in Radiation Therapy for Distal Extremities

In radiation therapy (RT) for skin cancer, tissue-equivalent substances called boluses are widely used to ensure the delivery of an adequate dose to the skin surface and to provide a radioprotective effect for normal tissue. The aim of this study was to develop a new type of three-dimensional (3D) bolus for RT involving body parts with irregular geometries and to evaluate its clinical feasibility. Two 3D-printed boluses were designed for two patients with squamous cell carcinoma (SCC) of their distal extremities based on computed tomography (CT) images and printed with polylactic acid (PLA). The clinical feasibility of the boluses was evaluated by measuring the in vivo skin dose at the tumor site with optically stimulated luminescence detectors (OSLDs) and comparing the results with the prescribed and calculated doses from the Eclipse treatment planning system (TPS). The average measured dose distribution for the two patients was 94.75% of the prescribed dose and 98.8% of the calculated dose. In addition, the average measured dose during repeated treatments was 189.5 ± 3.7 cGy, thus demonstrating the excellent reproducibility of the proposed approach. Overall, the customized 3D-printed boluses for the RT of distal extremities accurately delivered doses to skin tumors with improved reproducibility.

Hemodynamic and Rhythmologic Effects of Push-Dose Landiolol in Critical Care-A Retrospective Cross-Sectional Study.

The highly β1-selective beta-blocker Landiolol is known to facilitate efficient and safe rate control in non-compensatory tachycardia or dysrhythmia when administered continuously. However, efficacy and safety data of the also-available bolus formulation in critically ill patients are scarce. We conducted a retrospective cross-sectional study on a real-life cohort of critical care patients, who had been treated with push-dose Landiolol due to sudden-onset non-compensatory supraventricular tachycardia. Continuous hemodynamic data had been acquired via invasive blood pressure monitoring. Thirty patients and 49 bolus applications were analyzed. Successful heart rate control was accomplished in 20 (41%) cases, rhythm control was achieved in 13 (27%) episodes, and 16 (33%) applications showed no effect. Overall, the heart rate was significantly lower (145 (130-150) vs. 105 (100-125) bpm, p < 0.001) in a 90 min post-application observational period in all subgroups. The median changes in blood pressure after the bolus application did not reach clinical significance. Compared with the ventilation settings before the bolus application, the respiratory settings including the required FiO2 after the bolus application did not differ significantly. No serious adverse events were seen. Push-dose Landiolol was safe and effective in critically ill ICU patients. No clinically relevant impact on blood pressure was noted.

Impact of Respiratory Motion on the Skin Dose for Breast Cancer in Tomotherapy: A Study in the In-house Moving Phantom.

Purpose: The dose expansion methods as the skin flash and virtual bolus were used to solve intrafraction movement for breast planning due to breathing motion. We investigated the skin dose in each planning method by using optically stimulated luminescence on an in-house moving phantom for breast cancer treatment in tomotherapy. The impact of respiratory motion on skin dose between static and dynamic phantom's conditions was evaluated. Methods: A phantom was developed with movement controlled by the respirator for generating the respiratory waveforms to simulate respiratory motion. Five optically stimulated luminescence dosimeters were placed on the phantom surface to investigate the skin dose for the TomoDirect and TomoHelical under static and dynamic conditions. Eight treatment plans were generated with and without skin flash or virtual bolus by varying the thickness. The difference in skin dose between the two phantom conditions for each plan was explored. Results: All plans demonstrated a skin dose of more than 87% of the prescription dose under static conditions. However, the skin dose was reduced to 84.1% (TomoDirect) and 78.9% (TomoHelical) for dynamic conditions. The treatment plans without skin flash or virtual bolus showed significant skin dose differences under static and dynamic conditions by 4.83% (TomoDirect) and 9.43% (TomoHelical), whereas the skin flash with two leaves (TomoDirect 2L) or virtual bolus of at least 1.0 cm thickness (VB1.0) application compensated the skin dose in case of intrafraction movements by presenting a skin dose difference of less than 2% between the static and dynamic conditions. Conclusion: The skin dose was reduced under dynamic conditions due to breathing motion. The skin flash method with TomoDirect 2L or virtual bolus application with 1.0 cm thickness was useful for maintaining skin dose following the prescription by compensating for intrafraction movement due to respiratory motion for breast cancer in tomotherapy.

Dose verification of virtual bolus application for helical tomotherapy.

The objective of the study is to verify the dose delivered on helical tomotherapy based on treatment plan with varying virtual bolus (VB) thickness. The target was localized on the ArcCHECK image by 3 mm margin from the phantom surface. The dimension of target, which includes the ArcCHECK's detectors, with the 4.0 cm width and length 12.0 cm along the phantom The 5 treatment plans were generated, 1 plan without VB application (NoVB) and the 4 plans with varying of VB thickness on the phantom surface by 0.5 cm (VB0.5), 1.0 cm (VB1.0), 1.5 cm (VB1.5), and 2.0 cm (VB2.0), in treatment planning but absent during irradiation. For measurement analysis, the ionization chamber and the ArcCHECK detectors were used for point dose and dose distribution by investigating the percentage of dose difference and the gamma passing rate. The VB thickness 0.5, 1.0 and 1.5 cm showed acceptable value with less than 2% for dose difference by 0.37% (VB0.5), -0.11% (VB1.0) and -0.37% (VB1.5) at the center of ArcCHECK. The accuracy of dose distribution showed an acceptable gamma passing rate of 99.8% (VB0.5), 100% (VB1.0), and 90.2% (VB1.5) for gamma criteria by 3%/3mm for absolute dose analysis. However, the gamma passing rate of VB2.0 down to 71.2% of absolute mode for gamma criteria by 3%/3mm. The treatment plans with VB thickness less than 15 mm deliver doses that are comparable to treatment plans without virtual bolus based on gamma analysis. However, the deviation showed a trend increasing when VB thickness increased. The VB2.0 was not acceptable for point dose and dose distribution verification by more than 2% dose difference and less than 90% of gamma passing rate.

Application note for the use of a wireless device measuring reticular pH under practice conditions in a Swiss dairy herd

Subacute ruminal acidosis (SARA) is caused by ingestion of diets high in rapidly fermentable carbohydrates and/or deficient in physically active fiber, often suspected to occur in high yielding dairy cows. Although SARA has been defined as repeatedly occurring periods of low ruminal pH, both practical measuring methods and threshold values remain subject to research.Precision livestock farming comprises use of real-time monitoring and managing systems for livestock farmers. Reticular pH can be monitored continuously on individual cow level by use of an indwelling bolus situated in the reticulum, linked to a wireless data transmission system. Practical experience in use of such boluses is scarce. The first aim of this field application was to test a commercially available bolus under field conditions in a dairy herd, and to assess the data obtained on herd level. The second aim was to suggest criteria indicative of SARA on herd level. The threshold for this investigation was set at pH ≤ 5.5 for ≥ 3 h, simultaneously occurring in ≥ 3 cows, by combining a testing strategy and a threshold from two peer-reviewed publications.Of 15 boluses administered, 12 (80%) provided reliable data. Reticular pH was measured in 10-min intervals. Useful data were obtained during the first 80 days after bolus application. This was considerably lower than the 150 days as described by the manufacturer.Based on pH measurements, a mean individual pH curve for each cow was created through grouping pH values for each time point over the entire period. The mean individual curve showed a circadian pH change with low pH values in the evening and variation of mean individual pH values among cows. No event of three cows simultaneously showing a reticular pH ≤ 5.5 during a ≥ 3 h interval was recorded. Maximum time span during which pH was ≤ 5.5 in an individual cow was 4 h and 40 min.We conclude that use of the system on herd level is appropriate. Establishing a herd-level threshold for SARA based on continuous measuring systems requires integration of the mean individual pH curve, the individual minimal pH values, and the time span of low reticular pH.

The effect of post-reperfusion levosimendan in an experimental intestinal ischemia–reperfusion model

BackgroundLevosimendan has been reported to have a positive effect on ischemia–reperfusion injury. Herein, we aimed to evaluate the effects of levosimendan applied after reperfusion in an experimental intestinal injury-reperfusion (IR) model.MethodsTwenty-one Wistar-albino male rats were separated into three groups: Sham group (n = 7): solely superior mesenteric artery (SMA) was dissected after laparotomy; intestinal ischemia–reperfusion group (IIR, n = 7): SMA was clamped for 60 min and unclamped for 120 min to cause ischemia–reperfusion; IIR + levosimendan group (IIR + L, n = 7): levosimendan was administered in ischemia–reperfusion model. The mean arterial pressures (MAP) were measured in all groups. MAP measurements were performed at the end of stabilization, at the 15th, 30th, and 60th minute of ischemia; at the 15th, 30th, 60th, and 120th minute of reperfusion; and at the end of levosimendan bolus application and when levosimendan infusion concluded. Reperfusion injury was evaluated with tissue malondialdehyde (MDA) and by Chiu score.ResultsMAP at 15 min, 30 min, and 60 min of reperfusion was lower in IIR and IIR + L groups compared with basal inter-group measurements. Decline in MAP at 30 min after reperfusion was statistically significant in IIR and IIR + L groups when compared with the sham group. There was no significant difference between MDA levels in the groups. Chiu score was significantly lower in the sham group when compared to IIR and IIR + L groups and higher in IIR when compared to the IIR + L group.ConclusionLevosimendan leads to a decrease in intestinal damage although it did not affect lipid peroxidation and MAP when administered after reperfusion in an experimental intestinal IR model.

A Novel method of Bolus application in Hyperthermia of very extended Superficial Tumors

A Novel method of Bolus application in Hyperthermia of very extended Superficial Tumors

The Braking KV1/D‐type Potassium Channels Regulate the Excitability of Bronchopulmonary Vagal Afferent Nerves

The proper function of airway vagal afferent nerves is essential for the dynamic regulation of breathing and initiation of adequate airway defensive reflexes. A better understanding of the mechanisms controlling their activation bears physiological and pathological significance. The voltage‐gated potassium (KV) channels exert powerful controls on the neuronal excitability. Yet their expression and functions in the bronchopulmonary vagal afferent neurons remain largely unexplored. In this study we characterized the expression profile and inhibitory function of α‐dendrotoxin (α‐DTX)‐sensitive D‐type K+ channels composed of members of KV1subfamily of α‐subunits in mouse bronchopulmonary nodose neurons using a combination of single‐neurons RT‐PCR, patch clamp recording, ex‐vivo extracellular recording and two‐photon microscopic Ca2+ imaging techniques. The results showed that the vast majority of retrogradely labeled lung‐specific nodose neurons expressed Kcna1, 2 and 6 coding for the α‐DTX‐sensitive KV1.1, 1.2 and 1.6 α‐subunits, respectively. The D‐type K+ current (IK.D), defined as the α‐DTX‐sensitive K+ current, was recorded in 14/15 bronchopulmonary nodose neurons. It started to be activated at ‐65.7±4.3 mV with 50% channel activation at ‐24 ± 14 mV. IK.D opened rapidly in response to depolarization (activation time constants &lt;10 ms at voltage ≥‐15 mV), and displayed no inactivation during 600 ms at subthreshold/ threshold voltages and little or slow inactivation at more positive potentials (≥‐5 mV). Inhibition of IK.D with 50 nM α‐DTX depolarized mouse pulmonary nodose neurons, increased input resistance, lowered the minimal depolarizing current needed to evoke an action potential, and increased the number and frequency of action potential firing in response to depolarizing current injections. Application of a bolus of 100 nM α‐DTX to the afferent terminals in the mouse lungs via trachea led to overt activation in 49% of capsaicin‐sensitive nodose neurons and in 32% of capsaicin‐insensitive nodose neurons as detected by two‐photon microscope. Further study with extracellular recording revealed that the application of an α‐DTX bolus evoked action potential discharges in 8/19 (42%) nodose C‐fibers terminating in the mouse lungs with a peak firing frequency of 4.4 ± 3.9 Hz. These results indicate that both the soma and terminals of bronchopulmonary nodose afferent nerves express functional IK.D characterized by low‐threshold, fast activation, and lack of or slow inactivation. With these unique biophysical properties, IK.D channels act as an activation brake on the airway vagal afferent nerves by stabilizing the resting membrane potential and by counterbalancing the subthreshold depolarizing forces. Down‐regulation of IK.D, as occurs in many inflammatory diseases, may result in a heightened excitability of airway vagal afferent nerves causing exaggerated dyspnea, excessive mucous secretion, bronchoconstriction and chronic unproductive coughs associated with airway inflammation.

5‐HT7 Receptors Mediate Dilation of Rat Cremaster Muscle Arterioles in vivo

Serotonin (5‐HT) infusion in vivo causes hypotension and a fall in total peripheral resistance (TPR) that is mediated by 5‐HT7 receptors. 5‐HT dilates small arterioles in skeletal muscle, a microcirculation that importantly contributes to TPR. However, the receptors that mediate this dilation have not been established. Therefore, we tested the hypothesis that 5‐HT7 receptors mediate the arteriolar dilation in the skeletal muscle microcirculation. Cremaster muscles of isoflurane‐anesthetized male Sprague‐Dawley rats were prepared for digital in vivo microscopy and superfused with physiological salt solution (PSS) at 34 °C. Bolus (1‐10 nmols) application of 5‐HT into the superfusate caused substantial dilation of 3rd to 5th order arterioles from 10 ± 1 to 27 ± 1 μm (n = 10 arterioles from 4 rats, p &lt;0.0001) that recovered within 2‐3 min. Dilation to bolus application of 5‐HT was inhibited by superfusion with 1 μM SB269970, a selective 5‐HT7 receptor antagonist (diameter in SB = 9 ± 1 μm; diameter in SB + 5‐HT = 10 ± 1 μm; n = 10 arterioles from 4 rats; p = 0.8763). Similarly, steady‐state superfusion with 10‐30 nM of the 5‐HT1/7 receptor agonist 5‐carboxamidotryptamine (5‐CT) dilated 3rd‐5th‐order arterioles from 16 ± 3 to 37 ± 5 μm (n = 7 arterioles from 3 rats, p = 0.0004). This dilation was reversed (diameter in 1 μM SB269970 = 13 ± 2 μm, n = 7, p = 0.1479 vs. baseline) or blocked (diameter in 1 μM SB269970 + 10‐30 nM 5‐CT = 10 ± 2 μm, n = 7, p = 0.0005 vs. 5‐CT alone) by 1 μM SB269970. Dilation of arterioles to the muscarinic agonist, methacholine (MCH) was not inhibited by SB269970 verifying the specificity of the antagonist; arterioles dilated from 13 ± 2 μm to 25 ± 2 μm to 100 nmols MCH and dilated from 9 ± 2 μm to 32 ± 2 μm in response to MCH in the presence of 1 μM SB269970; n = 10 arterioles from 4 rats; p = 0.7232 vs. dilation in the absence of SB269970. Consistent with these data, pooled samples (4‐5 rats) of 1st and 2nd – order cremaster arterioles expressed message for 5‐HT7 receptors by quantitative real‐time PCR (CT = 36.4 ± 0.74, n = 3 pooled samples, p = 0.039 vs CT = 40). These data support our hypothesis that 5‐HT7 receptors mediate dilation of small arterioles in skeletal muscle and likely contribute to the observed hypotension when these receptors are engaged in vivo.

L’ulcère de Mooren: une cause rare parfois grave d’ulcération cornéenne périphérique!

Mooren´s ulcer is a rare form of peripheral corneal ulceration. The ulcer originates from an inflammatory infiltrate involving the limbal cornea. The disease spreads circumferentially, resulting in ulceration that progresses around the limbo and then centrally. Treatment is based on local steroidal anti-inflammatory drugs and conjunctival resection, amniotic membrane transplant and, in patients with severe perforation, on lamellar corneo-scleral transplant and appropriate immunosuppressive therapy. We here report the case of a male patient aged 55 years with nasal corneal ulceration involving the limbus. Ulceration extended circumferentially and centrally and was complicated by a perforation measuring 2.5 mm in vertical diameter with iris hernia. Possible causes of vasculitis were eliminated. The diagnosis Mooren´s ulcer was made. The patient received bolus application of corticosteroids and was referred for lamellar corneo-scleral transplant.

Potential of a rumen bolus containing 1,25-dihydroxyvitamin D3 glycosides for the prevention of hypocalcaemia in primiparous and multiparous dairy cows

Periparturient hypocalcaemia is a widespread metabolic disorder in dairy cows. Clinical and subclinical cases occur primarily in multiparous (Multi) cows, but subclinical cases have also been reported in primiparous (Primi) cows. A preventive strategy was investigated by administering the physiologically active vitamin D3 metabolite, 1,25-dihydroxyvitamin D3 (1,25-dihydroxycholecalciferol, 1,25(OH)2D3) as a rumen bolus. The bolus contained tablets of 1,25(OH)2D3 glycoside extract from Solanum glaucophyllum (SGE), releasing SGE over several days. The aim was to study the effect of a bolus containing 0 (C) or 500 µg (SGE) of 1,25(OH)2D3 on 1,25(OH)2D3 and mineral status in periparturient cows up to three weeks into lactation and on colostrum, milk and calves’ blood mineral contents. The bolus was administered three to four days prior to expected calving to Primi and Multi cows fed a herbage-based diet (dietary cation-anion difference of +522 mEq/kg DM). One C or SGE bolus was applied to 12 Primi and 12 Multi cows. Blood was regularly sampled (and selected a posteriori for antepartum samples) in regard to the actual calving day (d0), immediately prior to bolus application and at day −2, 0.5, 1, 1.5, 2, 4, 8, 11, 15, 18 and 22. Additional samples included urine (at bolus application, d0.5 and d2), colostrum, milk samples (weekly) and calves’ blood (d2). Blood serum 1,25(OH)2D3 increased between d0.5 and d2 in Primi-SGE, but remained unchanged in Primi-C, as did parathyroid hormone (PTH) and Ca in all Primi. Urinary Ca of Primi-SGE was increased on d2, indicating regulation of Ca excess. Three Multi-C cows with confirmed clinical hypocalcaemia needed treatment and thus were excluded from the dataset and replaced. Blood serum 1,25(OH)2D3 and PTH increased while Ca dropped by 40% between d0.5 and d2 in Multi-C, whereas 1,25(OH)2D3, Ca and PTH remained unchanged in Multi-SGE. Blood serum carboxyterminal telopeptide of type I collagen was higher in Primi than in Multi and increased with time, except in Primi-C. Mineral contents in colostrum, milk and blood serum of calves were not influenced to a relevant degree. In conclusion, Primi-C did not, in contrast to Multi-C, develop subclinical hypocalcaemia (<2.0 mmol Ca/l). Prevention of hypocalcaemia with one SGE bolus applied three to four days prior to expected calving was successful in maintaining blood Ca within normal range in Multi over the critical first two days and up to the first three weeks of lactation, without any observed detrimental effects on cows or calves.

Age Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries.

Endothelial dysfunction (ED) comes with age, even without overt vessel damage such as that which occurs in atherosclerosis and diabetic vasculopathy. We hypothesized that aging would affect the downstream signalling of the endothelial nitric oxide (NO) system in the vascular smooth muscle (VSM). With this in mind, resistance mesenteric arteries were isolated from 13-week (juvenile) and 40-week-old (aged) mice and tested under isometric conditions using wire myography. Acetylcholine (ACh)-induced relaxation was reduced in aged as compared to juvenile vessels. Pretreatment with L-NAME, which inhibits nitrix oxide synthases (NOS), decreased ACh-mediated vasorelaxation, whereby differences in vasorelaxation between groups disappeared. Endothelium-independent vasorelaxation by the NO donor sodium nitroprusside (SNP) was similar in both groups; however, SNP bolus application (10−6 mol L−1) as well as soluble guanylyl cyclase (sGC) activation by runcaciguat (10−6 mol L−1) caused faster responses in juvenile vessels. This was accompanied by higher cGMP concentrations and a stronger response to the PDE5 inhibitor sildenafil in juvenile vessels. Mesenteric arteries and aortas did not reveal apparent histological differences between groups (van Gieson staining). The mRNA expression of the α1 and α2 subunits of sGC was lower in aged animals, as was PDE5 mRNA expression. In conclusion, vasorelaxation is compromised at an early age in mice even in the absence of histopathological alterations. Vascular smooth muscle sGC is a key element in aged vessel dysfunction.

Evaluation of myocardial reperfusion in patients undergoing cangrelor supported primary PCI for STEMI

Abstract Background Optimal myocardial reperfusion is the main goal of pharmaco-invasive treatment in STEMI patients. Cangrelor is a new intravenous P2Y12 inhibitor, mainly used in intra-procedural PCI setting of STEMI patients. Intracoronary cangrelor bolus application results in high local drug concentrations and may be more effective than a standard intravenous bolus. Aim This study aims to investigate the potential benefits of intracoronary versus intravenous cangrelor bolus in STEMI patients undergoing to primary PCI (p-PCI). Materials and methods Overall, 71 consecutive STEMI patients undergoing p-PCI were treated with intracoronary (n=37) or intravenous (n=34) bolus cangrelor administration with subsequent 2-hour intravenous infusion. The primary end point was ST-elevation reduction (STR) ≥50% at 30 minutes and at 24 hours after p-PCI. Secondary end points were STR ≥70% at 30 min after p-PC, TIMI frame count, and the QT dispersion (QTd). Moreover, stent thrombosis, bleeding events according to BARC classification, and 30-day mortality have been evaluated as safety explorative end points. Results STEMI patients treated with intravenous Cangrelor bolus had a higher rate of STR ≥50% either at 30 minutes (72% vs. 45%; p=0.033) or at 24 hours after p-PCI (87.1% vs. 63.6%; p=0.030) as compared to patients treated with intracoronary Cangrelor bolus; similarly, STR ≥70% at 30 minutes was more frequent in the intravenous bolus group as compared to intracoronary one (67% vs. 29% p=0.02). Furthermore, multivariable analysis demonstrated that intravenous Cangrelor bolus administration was an independent predictor of STR ≥50% (OR 3.586; 95% CI 1.134 to 11.335; p=0.030). No differences according to the TIMI frame count and the QTd were found. No stent thrombosis were observed at 30 days. The incidence of mortality and bleeding events (BARC 3–5) were comparable among study groups (30 days-death: 2.9% vs 5.4%, p=0.606; BARC 3–5 bleedings: 17.6% vs 13.5% p=0.630). Conclusion Intravenous coronary bolus administration of cangrelor in primary PCI is superior to intracoronary treatment with respect to extent of microvascular obstruction, and perfusion. Funding Acknowledgement Type of funding sources: None.