Update on the Diagnosis and Management of Acute Colonic Pseudo-obstruction (ACPO).

PURPOSE OF REVIEW: Acute Colonic Pseudo-obstruction (ACPO) is a cause of large intestinal dilation and obstruction without any physical transition point. It remains difficult to diagnose and treat. We review the recent updates on diagnosis and management of ACPO. RECENT FINDINGS: Recent guidelines have posited that conservative management can be tried in most cases of ACPO, but that early decompression and surgery should be considered. Use of neostigmine is still a viable option but there is also promising data on pyridostigmine as well as prucalopride. Resolution of ACPO should be followed by daily use of polyethylene glycol (PEG) to help prevent recurrence. ACPO warrants early and accurate diagnosis with exclusion of alternate causes of large bowel dilation. Conservative management can be attempted for 48-72 h in those with cecal diameters < 12 cm and without signs of peritonitis and perforation. Early escalation of management should be attempted with neostigmine followed by endoscopy and/or surgery as needed, given that longer periods of dilation are associated with worse outcomes. There is promising new evidence for use of pyridostigmine and prucalopride, but further trials are needed prior to incorporating them into regular use. Finally, studies are lacking regarding prevention of ACPO after initial resolution.

Postoperative interventions for preventing bladder dysfunction after radical hysterectomy in women with early-stage cervical cancer.

BACKGROUND: Bladder dysfunction is a common complication following radical hysterectomy, caused by the damage to pelvic autonomic nerves that innervate the muscles of the bladder, urethral sphincter, and pelvic floor fasciae. Bladder dysfunction increases the rates of urinary tract infection, hospital visits or admission, and patient dissatisfaction. In addition, bladder dysfunction can also negatively impact patient quality of life (QoL). Several postoperative interventions have been proposed to prevent bladder dysfunction following radical hysterectomy. To our knowledge, there has been no systematic review evaluating the effectiveness and safety of these interventions for preventing bladder dysfunction following radical hysterectomy in women with cervical cancer. OBJECTIVES: To evaluate the effectiveness and safety of postoperative interventions for preventing bladder dysfunction following radical hysterectomy in women with early-stage cervical cancer (stage IA2 to IIA2). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 4) in the Cochrane Library, MEDLINE via Ovid (1946 to April week 2, 2020), and Embase via Ovid (1980 to 2020, week 16). We also checked registers of clinical trials, grey literature, conference reports, and citation lists of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating the effectiveness and safety of any type of postoperative interventions for preventing bladder dysfunction following a radical hysterectomy in women with stage IA2 to IIA2 cervical cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently selected potentially relevant RCTs, extracted data, assessed risk of bias, compared results, and made judgments on the quality and certainty of the evidence. We resolved any disagreements through discussion or consultation with a third review author. Outcomes of interest consisted of spontaneous voiding recovery one week after the operation, quality of life (QoL), adverse events, post-void residual urine volume one month after the operation, urinary tract infection over the one month following the operation, and subjective urinary symptoms. MAIN RESULTS: We identified 1464 records as a result of the search (excluding duplicates). Of the 20 records that potentially met the review criteria, we included five reports of four studies. Most of the studies had unclear risks of selection and reporting biases. Of the four studies, one compared bethanechol versus placebo and three studies compared suprapubic catheterisation with intermittent self-catheterisation. We identified two ongoing studies. Bethanechol versus placebo The study reported no information on the rate of spontaneous voiding recovery at one week following the operation, QoL, adverse events, urinary tract infection in the first month after surgery, and subjective urinary symptoms for this comparison. The volume of post-void residual urine, assessed at one month after surgery, among women receiving bethanechol was lower than those in the placebo group (mean difference (MD) -37.4 mL, 95% confidence interval (CI) -60.35 to -14.45; one study, 39 participants; very-low certainty evidence). Suprapubic catheterisation versus intermittent self-catheterisation The studies reported no information on the rate of spontaneous voiding recovery at one week and post-void residual urine volume at one month following the operation for this comparison. There was no difference in risks of acute complication (risk ratio (RR) 0.77, 95% CI 0.24 to 2.49; one study, 71 participants; very low certainty evidence) and urinary tract infections during the first month after surgery (RR 0.77, 95% CI 0.53 to 1.13; two studies, 95 participants; very- low certainty evidence) between participants who underwent suprapubic catheterisation and those who underwent intermittent self-catheterisation. Available data were insufficient to calculate the relative measures of the effect of interventions on QoL and subjective urinary symptoms. AUTHORS' CONCLUSIONS: None of the included studies reported rate of spontaneous voiding recovery one week after surgery, time to a post-void residual volume of urine of 50 mL or less, or post-void residual urine volume at 6 and 12 months after surgery, all of which are important outcomes for assessing postoperative bladder dysfunction. Limited evidence suggested that bethanechol may minimise the risk of bladder dysfunction after radical hysterectomy by lowering post-void residual urine volume. The certainty of this evidence, however, was very low. The effectiveness of different types of postoperative urinary catheterisation (suprapubic and intermittent self-catheterisation) remain unproven.

Comparison of the Effects of Neostigmine and Sugammadex on Colonic Anastomotic Strength in Rats.

BACKGROUND: After colorectal surgery, anastomotic leakage is a major cause of mortality and morbidity. There are many factors affecting anastomotic leakage. It is known that agents such as neostigmine that is used to reverse neuromuscular blockade have certain effects on anastomosis. In our study, in which we planned to test this hypothesis, we aimed to compare the possible effects of different doses of sugammadex and neostigmine on colon anastomosis strength in a colonic resection anastomosis model in rats. MATERIALS AND METHODS: Forty adult Wistar albino male rats were divided into five groups as control (group C), Sugammadex 16 mg/kg (group SL), sugammadex 96 mg/kg (group SH), neostigmine 0.3 µmol/kg (group NL), and neostigmine 1.5 µmol/kg (group NH). The transverse colons of all rats were resected, and colonic anastomosis was performed. Appropriate drug doses according to the groups were given on the postoperative seventh day, and tissue hydroxyproline (TH) level and anastomotic bursting pressure were measured. RESULTS: Anastomotic bursting pressure values were statistically significantly different between the groups (P = 0.001). The bursting pressure in group SH was significantly higher compared with group C, group NL, and group NH. The hydroxyproline values were statistically significantly different between the groups (P = 0.015). According to the post hoc test results, the difference was between group SH and group C (P = 0.007). There were no significant differences between the other groups (P > 0.05). There was no significant difference in terms of intra-abdominal adhesion rates between the groups. CONCLUSIONS: In our study, we found that low and high doses of neostigmine had no variable effect on anastomosis, but high dose of sugammadex (96 mg/kg) had an increasing effect on intestinal anastomosis strength.

Evaluation of Neuromuscular Blockade Reversal on Postoperative Mechanical Ventilation Time in a Cardiovascular Surgery Population.

OBJECTIVE: To report on postoperative outcomes related to the administration of neostigmine for reversal of nondepolarizing neuromuscular blocking agents in cardiovascular surgery patients, with a specific focus on the duration of postoperative mechanical ventilation as the primary endpoint. DESIGN: A retrospective cohort study design was followed to achieve the study objectives. SETTING: This was a single-center, chart review study conducted at a large academic medical center of adult patients post-cardiovascular surgery. PARTICIPANTS: Patients were included if they had received a bolus dose of perioperative nondepolarizing neuromuscular blocking agent and underwent one of the targeted cardiovascular surgeries. INTERVENTIONS: Final analysis comprised of 175 patients, 95 of whom received neostigmine and 80 who did not receive neostigmine. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the duration of postoperative mechanical ventilation. When controlling for all covariates, neostigmine use was associated with a 0.34-hour reduction (∼20.4 min) in duration of mechanical ventilation (parameter estimate: 0.66, 95% confidence interval 0.49-0.89; p = 0.0071). More patients who received neostigmine met the early extubation benchmark of less than 6 hours (55 v 34 patients; p = 0.04). Finally, neostigmine use was not found to be associated with increased risk of respiratory complications or postoperative nausea and/or vomiting. CONCLUSIONS: The use of neostigmine was found to have a protective effect on the duration of postoperative mechanical ventilation without increasing the risk of adverse complications.

A randomized-controlled, double-blind study to evaluate the efficacy of caudal midazolam, ketamine and neostigmine as adjuvants to bupivacaine on postoperative analgesic in children undergoing lower abdominal surgery.

• Background: Caudal epidural is the most commonly used technique for the management of postoperative pain in children. The aim of the present study was to assess and compare the efficacy of caudal bupivacaine as a postoperative analgesic alone or combined with midazolam, ketamine, and neostigmine in pediatric patients undergoing lower abdominal surgery. METHODS: Eighty pediatric patients categorized under the American Society of Anesthesiologists Physical Status I and II Classification System, who have been scheduled to undergo lower abdominal surgery were randomly designated into four groups to receive caudal block with either 1 ml/kg of 0.25% caudal bupivacaine for group B, 1 ml/kg of 0.25% caudal bupivacaine mixed with 2 µg/kg neostigmine for group BN, 1 ml/kg of 0.25% caudal bupivacaine mixed with 0.5 mg/kg ketamine for group BK or 1 ml/kg of 0.25% caudal bupivacaine mixed with 50 mcg/kg midazolam for group BM. Postoperative analgesia was examined by a blinded anesthetist utilizing a Revised Faces Pain Scale.Consumption of the total amount of rescue analgesic each 24 h, postoperative time to requirement of the first dose and any adverse effects were noted. RESULTS: The four groups were comparable as regards age, sex, weight, duration of surgery, heart rate, blood pressure and the time from induction of anesthesia to response to voice. The Revised Faces Pain Scale was 2.6±1.5 in group BN, 3.1±1.8 in group BM, 4.4±2.4 in group BK, and 5.6±1.3 in group B (p=0.005). Postoperative duration of analgesia was 433±68 min, 769±118 min, 1097±126 min and 1254±176 min in groups B, BK, BM and BN respectively (P=0.001). The dose of rescue analgesic within 24 h in group B was significantly higher than those of the other three groups (P<0.05). CONCLUSION: Addition of either neostigmine, midazolam, or ketamine to caudal bupivacaine extended analgesia time and decreased rescue analgesic compared to bupivacaine alone in children who underwent lower abdominal surgery.

Possible role of hydrogen sulfide as an endogenous relaxation factor in the rat bladder and prostate.

AIMS: To clarify the roles of hydrogen sulfide (H2 S), an endogenous gasotransmitter, in the rat bladder and prostate, we investigated the distribution of enzymes related to H2 S biosynthesis (cystathionine ß-synthase [CBS], cystathionine γ-lyase [CSE], 3-mercaptopyruvate sulfurtransferase [MPST], cysteine aminotransferase [CAT], and D-amino acid oxidase [DAO]) and the content of H2 S. We also investigated the effects of H2 S donors (NaHS and GYY4137) on the contractility of both tissues and on micturition. METHODS: The distribution of these enzymes was investigated by real-time PCR, Western blot, and immunohistochemistry. Tissue H2 S content was measured by the methylene blue method. The effects of NaHS (1 × 10-9 to 3 × 10-4 M) were evaluated on carbachol (10-5 M)-induced pre-contracted bladder strips, and on noradrenaline (10-5 M)-induced pre-contracted prostate strips, which were pretreated with propranolol (10-6 M). In addition, in urethane-anesthetized male Wistar rats, the effects of intravesically instilled GYY4137 (10-8 , 10-7 , and 10-6 M) on micturition were evaluated by cystometry. RESULTS: MPST and CAT were detected in the bladder and prostate, CBS was only detected in the prostate, while CSE and DAO were not detected in both tissues. Immunoreactivity of these enzymes was mainly detected in the urothelium and smooth muscle layer of the bladder and in the prostate glandular epithelium. H2 S was detected in both tissues. NaHS dose-dependently induced relaxation of pre-contracted bladder and prostate strips. Intravesically instilled GYY4137 significantly prolonged intercontraction intervals. CONCLUSIONS: It is possible that H2 S can function as an endogenous relaxation factor in the rat bladder and prostate.

Management of rocuronium neuromuscular block using a protocol for qualitative monitoring and reversal with neostigmine.

BACKGROUND: Neuromuscular block using subjective monitoring and neostigmine reversal is commonly associated with postoperative residual neuromuscular block. We tested whether a protocol for the management of neuromuscular block that specified appropriate dosing and optimal neostigmine reversal was associated with a reduction in postoperative residual neuromuscular block. METHODS: Rocuronium administration was guided by surgical requirements and based on the ideal body weight, with dose reductions for female sex and age >55 yr. Neostigmine was administered in adjusted doses after a train-of-four count of four was confirmed at the thumb. The protocol ensured a minimum of 10 min between neostigmine administration and tracheal extubation. We measured the postoperative residual neuromuscular block in patients undergoing abdominal surgery before and after introduction of the protocol. Pre-specified primary and secondary endpoints were incidence of postoperative residual neuromuscular block and severe postoperative residual neuromuscular block at the time of tracheal extubation, defined as normalised train-of-four ratios <0.9 and <0.7, respectively. RESULTS: The incidence of postoperative residual neuromuscular block at tracheal extubation was 14/40 (35%) for patients managed according to the protocol compared with 22/38 (58%) for patients in the control group, odds ratio of 0.39, and 95% confidence interval of 0.14-1.07; P=0.068. The incidence of severe postoperative residual neuromuscular block at tracheal extubation showed a highly significant difference, odds ratio=0.06, and confidence interval of 0.00-0.43; P=0.001. CONCLUSIONS: The incidence of severe postoperative residual neuromuscular block was significantly reduced after the protocol was introduced. Given the limitations inherent in this before-and-after study, further research is needed to confirm these results. CLINICAL TRIAL REGISTRATION: NCT02660398.

Are There Pharmacotherapeutic Options for Underactive Bladder?

Currently, underactive bladder, the symptom-based correlate of the urodynamic diagnosis of detrusor underactivity, has no effective drug treatments. Use of sympathomimetics, targeting cholinergic receptors, is not supported by current evidence. Several potential targets are the subject of ongoing investigation.

Sudden-onset unilateral ptosis induced by pituitary Macroadenoma, with false-positive jolly and neostigmine tests.

The development of ptosis as a consequence of pituitary tumor is an exceptionally rare occurrence. Here, we describe the case of sudden-onset unilateral ptosis induced by pituitary macroadenoma. The condition was characterized by false-positive Jolly and neostigmine tests. These findings mimic oculomotor nerve palsy and make the correct diagnostics rather challenging. The case points to the fact that patients with acquired ptosis need detailed neuroophthalmological examination.

Neostigmine and glycopyrronium: a potential safe alternative for patients with pseudo-obstruction without access to conventional methods of decompression.

Intestinal pseudo-obstruction mimics bowel obstruction. However, on examination, no mechanical cause is identified. This condition will often resolve when managed conservatively, yet in some cases decompression is required to avoid the serious complications of bowel ischaemia and perforation. This is performed endoscopically, and due to the invasive nature and limited access to this service, an alternative treatment option is deemed appealing. Neostigmine has good efficacy in the decompression of pseudo-obstruction but is hindered by its wide side effect profile. In this context, neostigmine requires careful monitoring, which limits its appeal. This side effect profile is minimised when neostigmine is administered in conjunction with glycopyrronium.This case demonstrates the novel use of neostigmine and glycopyrronium in decompression of the bowel in a patient with pseudo-obstruction. Furthermore, it highlights its value, particularly when conventional techniques for decompression are not accessible.

Effect of sugammadex versus neostigmine/atropine combination on postoperative cognitive dysfunction after elective surgery.

This study aimed to assess the effects of sugammadex and neostigmine/atropine on postoperative cognitive dysfunction (POCD) in adult patients after elective surgery. A randomised, double-blind controlled trial was carried out on 160 American Society of Anesthesiologists physical status I to III patients who were >40 years. The Mini-Mental State Evaluation, clock-drawing test and the Isaacs Set test were used to assess cognitive function at three timepoints: 1) preoperatively, 2) one hour postoperatively, and 3) at discharge. The anaesthetic protocol was the same for all patients, except for the neuromuscular block reversal, which was administered by random allocation using either sugammadex or neostigmine/atropine after the reappearance of T2 in the train-of-four sequence. POCD was defined as a decline ≥1 standard deviation in ≥2 cognitive tests. The incidence of POCD was similar in both groups at one hour postoperatively and at discharge (28% and 10%, in the neostigmine group, 23% and 5.4% in the sugammadex group, P=0.55 and 0.27 respectively). In relation to individual tests, a significant decline of clock-drawing test in the neostigmine group was observed at one hour postoperatively and at discharge. For the Isaacs Set test, a greater decline was found in the sugammadex group. These findings suggest that there are no clinically important differences in the incidence of POCD after neostigmine or sugammadex administration.

Regulating autonomic nervous system homeostasis improves pulmonary function in rabbits with acute lung injury.

BACKGROUND: This study aimed to investigate the effects of regulating autonomic nervous system (ANS) homeostasis by inhibiting sympathetic hyperactivity and/or enhancing parasympathetic activity on pulmonary inflammation and functional disturbance. METHODS: An animal model of acute lung injury (ALI) was established in rabbits by an intratracheal injection of hydrochloric acid (HCl) in rabbits. Animals in control groups were received saline or HCl only, and the others received both HCl and followed treatments: vagus nerve stimulation (VNS), intravenous injection of tetrahydroaminoacridine (THA), or stellate ganglion block (SGB). The effects of different treatments on the changes in autonomic nervous system homeostasis, pulmonary and systemic inflammation, and functional disturbance were detected. RESULTS: Sympathetic nervous activity was higher than parasympathetic nervous activity in rabbits after HCl aspiration, as demonstrated by the significant changes in the discharge frequency of cervical sympathetic/vagus trunk, and heart rate variability. VNS, THA and SGB could significantly alleviate the changes of ANS induced by HCl aspiration and improved the pulmonary function, especially for SGB treatment. CONCLUSIONS: The disturbance of ANS homeostasis is attributed to a predominance of SNS activity. Administration of VNS, THA and SGB are capable to regulate disequilibrium of the ANS in rabbits with HCl-induced ALI and SGB is supposed to be the most effective approach.

Use of neuromuscular blockers and neostigmine for general anesthesia and its association with neuraxial blockade: A retrospective study.

This research aimed to assess the use of neuromuscular blockers (NMB) and its reversal, associated or not with neuraxial blockade, after general anesthesia.This retrospective study analyzed 1295 patients that underwent surgery with general anesthesia at Prof. Dr. José Aristodemo Pinotti Hospital in 2013. The study included patients aged >1 year, with complete, readable medical charts and anesthetic records.Rocuronium (ROC) was the most used NMB (96.7%), with an initial dose of 0.60 (0.52-0.74) mg/kg and total dose of 0.38 (0.27-0.53) mg/kg/h. In 24.3% of the cases, neuraxial blockade was associated with a significantly longer anesthesia (P < .001) than in cases without neuraxial block, regardless of technique (total intravenous (TIV) vs intravenous and inhalational (IV+IN)). In 71.9% of the cases, a single dose of NMB was used. Patients under TIV general anesthesia associated with neuraxial blockade had a lower total dose of ROC (mg/kg/h) in comparison with TIV GA alone (0.30 (0.23-0.39) and 0.42 (0.30-0.56) mg/kg/h, respectively, P < .001). The same was observed for patients under IV+IN GA (0.32 (0.23-0.41) and 0.43 (0.31-0.56) mg/kg/h, respectively, P < .001). The duration of anesthesia was longer according to increasing number of additional NMB doses (P < .001). Dose of neostigmine was 2.00 (2.00-2.00) mg or 29.41 (25.31-33.89) µg/kg. The interval between neostigmine and extubation was >30 minutes in 10.9% of cases.The most widely used NMB was ROC. Neuroaxial blockade (spinal or epidural) was significantly associated with reduced total dose of ROC (mg/kg/h) during general anesthesia, even in the absence of neuromuscular monitoring and regardless of general anesthetic technique chosen. In most cases, neostigmine was used to reverse neuromuscular block. The prolonged interval between neostigmine and extubation (>30 minutes) was neither associated with total doses of ROC or neostigmine, nor with the time of NMB administration. This study corroborates the important role of quantitative neuromuscular monitors and demonstrates that neuraxial blockade is associated with reduced total ROC dose. Further studies are needed to evaluate the possible role of neuraxial blockade in reducing the incidence of postoperative residual curarization.

Menthol inhibiting parasympathetic function of tracheal smooth muscle.

Menthol is used as a constituent of food and drink, tobacco and cosmetics nowadays. This cold receptor agonist has been used as a nasal inhalation solution in the daily life. The effect of menthol on nasal mucosa in vivo is well known; however, the effect of the drug on tracheal smooth muscle has been rarely explored. Therefore, during administration of the drug for nasal symptoms, it might also affect the trachea via oral intake or inhalation. We used our preparation to test the effectiveness of menthol on isolated rat tracheal smooth muscle. A 5 mm long portion of rat trachea was submersed in 30 ml Krebs solution in a muscle bath at 37ºC. Changes in tracheal contractility in response to the application of a parasympathetic mimetic agent were measured using a transducer connected to a Pentium III computer equipped with polygraph software. The following assessments of menthol were performed: (1) effect on tracheal smooth muscle resting tension; (2) effect on contraction caused by 10-6 M methacholine as a parasympathetic mimetic; (3) effect of the drug on electrically induced tracheal smooth muscle contractions. Results indicated that addition of a parasympathetic mimetic to the incubation medium caused the trachea to contract in a dose-dependent manner. Addition of menthol at doses of 10-5 M or above elicited a relaxation response to 10-6 M methacholine-induced contraction. Menthol could also inhibit electrical field stimulation (EFS) induced spike contraction. However, it alone had a minimal effect on the basal tension of trachea as the concentration increased. We concluded that the degree of drug-induced tracheal contraction or relaxation was dose-dependent. In addition, this study indicated that high concentrations of menthol might actually inhibit parasympathetic function of the trachea.

Parasympathomimetic drugs for dry mouth due to radiotherapy.

Data sourcesCochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials, Medline, Embase and CINAHL databases. Reference lists of identified articles were checked and experts in the field and relevant pharmaceutical companies were contacted.Study selectionRandomised controlled trials, including parallel and crossover, carried out in any setting on any patient population with radiation-induced salivary dysfunction using parasympathomimetics drugs.Data extraction and synthesisThe two authors independently assessed for inclusion, established the risk of bias and abstracted data. The primary outcome was level of xerostomia. The authors intended to report risk ratio, odds ratio, risk difference and NNT for dichotomous data and mean difference and standard mean difference for continuous data.ResultsOf the three included studies, one (n=20) reported mean improvement on the VAS (22.5 mm on a 100 mm scale). The other two studies considered a change in 25 mm on the VAS a positive response. Of those one (n=207) reported positive response in 51% of subjects on 5mg of pilocapine TID and 47% for 10mg TID. The second (n= 162) reported a 42% positive response with a titrated dose regimen. The side effects rate was high,and the main reason for discontinuation.ConclusionsThere is limited evidence to support the use of pilocarpine hydrochloride in the treatment of radiation-induced xerostomia. Currently, there is little evidence to support the use of other parasympathomimetic drugs in the treatment of radiation-induced xerostomia. Available studies suggest that approximately half of patients will respond, but side effects can be problematic. The conclusions of the update are the same as the conclusions of the original review, since no new relevant studies have been published in the interim.

Ebselen does not improve oxidative stress and vascular function in patients with diabetes: a randomized, crossover trial.

Oxidative stress is a key driver of vascular dysfunction in diabetes mellitus. Ebselen is a glutathione peroxidase mimetic. A single-site, randomized, double-masked, placebo-controlled, crossover trial was carried out in 26 patients with type 1 or type 2 diabetes to evaluate effects of high-dose ebselen (150 mg po twice daily) administration on oxidative stress and endothelium-dependent vasodilation. Treatment periods were in random order of 4 wk duration, with a 4-wk washout between treatments. Measures of oxidative stress included nitrotyrosine, plasma 8-isoprostanes, and the ratio of reduced to oxidized glutathione. Vascular ultrasound of the brachial artery and plethysmographic measurement of blood flow were used to assess flow-mediated and methacholine-induced endothelium-dependent vasodilation of conduit and resistance vessels, respectively. Ebselen administration did not affect parameters of oxidative stress or conduit artery or forearm arteriolar vascular function compared with placebo treatment. There was no difference in outcome by diabetes type. Ebselen, at the dose and duration evaluated, does not improve the oxidative stress profile, nor does it affect endothelium-dependent vasodilation in patients with diabetes mellitus.

Effect of mesenchymal stem cells and galantamine nanoparticles in rat model of Alzheimer's disease.

AIM: The present study investigated the efficacy of bone marrow-derived mesenchymal stem cells (BM-MSCs) in combination with galantamine hydrobromide-loaded solid lipid nanoparticles (GH-SLNs) in intracerebroventricular (ICV)-isoproterenol-induced rat model of Alzheimer's disease. MATERIALS & METHODS: BM-MSCs were harvested by dissecting femur and tibia of 8-10-week-old Wistar rats. 1 × 10(6) cells were administered intravenously once in ICV-isoproterenol-induced rats followed by GH-SLNs (5 mg/kg) for 3 weeks. RESULTS & CONCLUSION: ICV-isoproterenol resulted in significant memory deficit. The results demonstrated rapid regain of memory in isoproterenol-induced amnesic rats, following single intravenous administration of BM-MSCs and oral administration of GH-SLNs for 21 days. The combination of BM-MSCs and GH-SLNs produced a more pronounced protective effect, therefore, could be explored for the management of Alzheimer's disease.

Comparison of neostigmine and sugammadex for hemodynamic parameters in cardiac patients undergoing noncardiac surgery.

STUDY OBJECTIVE: The aim of this study is to compare the hemodynamic effects of neostigmine-atropine combination and sugammadex in patients with cardiac problems undergoing noncardiac surgery. DESIGN: Prospective randomized study. SETTING: In the operating room. PATIENTS: Ninety patients with a class 2 or 3 cardiovascular disease according to the New York Heart Association classification and aged between 18 and 75 years undergoing noncardiac surgery were randomized. INTERVENTIONS: Group N (n = 45) received 0.03 mg/kg IV neostigmine when T2 appeared as measured with a nerve muscle stimulator. When heart rate was 5 beats/min (±10 beats/min) lower than the heart rate before administration of the medication, 0.5 mg IV atropine sulfate was given. Group S (n = 45) received 3 mg/kg IV sugammadex when T2 appeared as measured with a nerve muscle stimulator. MEASUREMENTS: Heart rate, mean systolic and diastolic blood pressures, and electrocardiographic alterations including the QTc (QT Fredericia and QT Bazett) were recorded. MAIN RESULTS: There were no significant differences between and within the groups in terms of QTc values. Sugammadex group had a significant decrease on heart rate 1 minute after the medication when compared to the measurement before the medication (P < .05). Heart rate and systolic blood pressure increased in neostigmine group 3 minutes after the medication and during postoperative measurements (P < .05). Sugammadex group had lower systolic, diastolic, and mean blood pressures and heart rate when compared to neostigmine group (P < .05). CONCLUSIONS: We suggest that sugammadex might be preferred as it provides more hemodynamic stability compared to neostigmine-atropine combination to reverse rocuronium-induced neuromuscular blockage in cardiac patients undergoing noncardiac surgery.

Impact of treatment strategies for open angle glaucoma on intraocular pressure: the RiGOR study.

AIMS: The RiGOR study's primary outcome measure was a 15% reduction in intraocular pressure (IOP) for patients with open-angle glaucoma at 1 year. METHODS: Patients received treatment according to the ophthalmologist's usual practice. RESULTS: A higher proportion of patients in the incisional and other surgery group achieved a 15% reduction in IOP than in the laser surgery or additional medication groups (82, 57, and 57% respectively). In multivariate regression analyses, incisional surgery patients were 2.7-times as likely as patients treated with additional medication to achieve a 15% reduction in IOP (odds ratio: 2.67; 95% CI: 2.01-3.57). CONCLUSION: Incisional and other surgical procedures are effective treatments. There were no differences in treatment response by race or ethnicity.

Parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy.

BACKGROUND: This is an updated version of the original Cochrane review on parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy (published in Issue 3, 2007). Salivary gland dysfunction is a predictable side effect of radiotherapy to the head and neck region. Pilocarpine hydrochloride (a choline ester) is licensed in many countries for the treatment of radiation-induced salivary gland dysfunction. Other parasympathomimetics have also been used 'off licence' in the treatment of this condition. OBJECTIVES: To determine the efficacy and tolerability of parasympathomimetic drugs in the treatment of radiation-induced salivary gland dysfunction (specifically radiation-induced xerostomia). SEARCH METHODS: For this update, we ran searches of the Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 6), MEDLINE, EMBASE, and CINAHL in July 2015. We checked the reference lists of retrieved articles for additional studies, contacted experts in the field for unpublished and ongoing trials, and contacted relevant pharmaceutical companies for unpublished and ongoing trials. SELECTION CRITERIA: The selection criteria for the review were: 1) randomised controlled trials; 2) people suffering from radiation-induced salivary gland dysfunction; 3) people treated with parasympathomimetic drugs; and 4) assessable data available on primary outcome measure. DATA COLLECTION AND ANALYSIS: The two review authors independently collected data from the full-text version of relevant papers including: 1) citation details; 2) participants; 3) interventions; 4) assessments; 5) outcomes (that is efficacy, tolerability); and 6) quality issues.Due to a lack of appropriate data, we were unable to perform a meta-analysis. MAIN RESULTS: In the original review, three studies, including a total of 298 participants, fulfilled the inclusion criteria. All three studies involved the use of pilocarpine hydrochloride. We have included no additional studies in the update of the review; we have excluded eight additional studies.The data suggest that pilocarpine hydrochloride is more effective than placebo and at least as effective as artificial saliva. The response rate was 42% to 51%. The time to response was up to 12 weeks. The overall side effect rate was high, and side effects were the main reason for withdrawal (6% to 15% of participants taking 5 mg three times a day had to withdraw). The side effects were usually the result of generalised parasympathomimetic stimulation (for example sweating, headaches, urinary frequency, vasodilatation). Response rates were not dose dependent, but side effect rates were dose dependent. AUTHORS' CONCLUSIONS: There is limited evidence to support the use of pilocarpine hydrochloride in the treatment of radiation-induced xerostomia. Currently, there is little evidence to support the use of other parasympathomimetic drugs in the treatment of radiation-induced xerostomia. Available studies suggest that approximately half of patients will respond, but side effects can be problematic. The conclusions of the update are the same as the conclusions of the original review, since no new relevant studies have been published in the interim.