Esophago-glottal closure reflex in human infants: a novel reflex elicited with concurrent manometry and ultrasonography

BACKGROUND AND AIMS: Our aims were to identify and characterize the glottal response to esophageal mechanostimulation in human infants. We tested the hypotheses that glottal response is related to the type of esophageal peristaltic response, stimulus volume, and respiratory phase. METHODS: Ten infants (2.8 kg, SD 0.5) were studied at 39.2 wk (SD 2.4). Esophageal manometry concurrent with ultrasonography of the glottis (USG) was performed. The sensory-motor characteristics of mechanostimulation-induced esophago-glottal closure reflex (EGCR, adduction of glottal folds upon esophageal provocation) were identified. Mid-esophageal infusions of air (N = 41) were given and the temporal relationships of glottal response with deglutition, secondary peristalsis (SP), and the respiratory phase were analyzed using multinomial logistic regression models. RESULTS: The frequency occurrence of EGCR (83%) was compared (P < 0.001) with deglutition (44%), SP (34%), and no esophageal responses (22%). The odds ratios (OR, 95% CI) for the coexistence of EGCR with SP (0.4, 0.06-2.2), deglutition (1.9, 0.1-26), and no response (1.9, 0.4-9.0) were similar. The response time for esophageal reflexes was 3.8 (SD 1.8) s, and for EGCR was 0.4 (SD 0.3) s (P < 0.001). Volume-response relationship was noted (1 mL vs 2 mL, P < 0.05). EGCR was noted in both respiratory phases; however, EGCR response time was faster during expiration (P < 0.05). CONCLUSION: The occurrence of EGCR is independent of the peristaltic reflexes or the respiratory phase of infusion. The independent existence of EGCR suggests a hypervigilant state of the glottis to prevent retrograde aspiration during GER events.     

Topical Tranexamic Acid Compared With Anterior Nasal Packing for Treatment of Epistaxis in Patients Taking Antiplatelet Drugs: Randomized Controlled Trial

Objective

We evaluated the efficacy of topical application of the injectable form of tranexamic acid (TXA) compared with anterior nasal packing (ANP) for the treatment of epistaxis in patients taking antiplatelet drugs (aspirin, clopidogrel, or both) who presented to the emergency department (ED).

Methods

A randomized, parallel‐group clinical trial was conducted at two EDs. A total of 124 participants were randomized to receive topical TXA (500 mg in 5 mL) or ANP, 62 patients per group. The primary outcome was the proportion of patients in each group whose bleeding had stopped at 10 minutes. Secondary outcomes were the rebleeding rate at 24 hours and 1 week, ED length of stay (LOS), and patient satisfaction.

Results

Within 10 minutes of treatment, bleeding was stopped in 73% of the patients in the TXA group, compared with 29% in the ANP group (difference = 44%, 95% confidence interval, 26% to 57%; p < 0.001). Additionally, rebleeding was reported in 5 and 10% of patients during the first 24 hours in the TXA and the ANP groups, respectively. At 1 week, 5% of patients in the TXA group and 21% of patients in the ANP group had experienced recurrent bleeding (p = 0.007). Patients in the TXA group reported higher satisfaction scores (median [interquartile range {IQR}], 9 [8–9.25]) compared with the ANP group (median [IQR] = 4 [3–5]; p < 0.001). Discharge from the ED in <2 hours was achieved in 97% of patients in the TXA group versus 13% in the ANP group (p < 0.001). There were no adverse events reported in either group.

Conclusions

In our study population, epistaxis treatment with topical application of TXA resulted in faster bleeding cessation, less rebleeding at 1 week, shorter ED LOS, and higher patient satisfaction compared with ANP.     

The Effect of Acute Lithium and Rubidium Pretreatment on Apomorphine-Induced Pecking in Pigeons

Abstract: The effects of different doses of lithium (5-320 mg/kg intramuscularly) and rubidium (0.25-32 mg/kg intramuscularly) on apomorphine-induced pecking were investigated in pigeons. These two cations did not induce pecking by itself. Intramuscular administration of apomorphine (a mixed D1/D2 dopamine receptors agonist, 0.1-1.6 mg/kg) induced pecking in a dose-dependent manner. SCH 23390 (Dl dopamine receptor antagonist, 0.02-0.08 mg/kg) and sulpiride (D2 dopamine receptor antagonist, 25-100 mg/kg) decreased apomorphine-induced pecking dose-dependently. Combination of SCH 23390 (0.04 mg/kg) with sulpiride (50 mg/kg) caused a stronger inhibitory effect on apomorphine response. This indicates that both Dl and D2 dopamine receptors are involved in apomorphine-induced pecking. The response induced by apomorphine (0.2-0.8 mg/kg) was decreased in animals pretreated with lithium and rubidium. In these conditions, SCH 23390 and sulpiride produced a larger inhibitory effect on the apomorphine response, suggesting that acute lithium and rubidium pretreatment inhibit pecking by interfering with dopaminergic mechanisms.     

Sulpiride injections into the medial septum reverse the influence of intra-medial septum injection of L-arginine on expression of place conditioning-induced by morphine in rats

Effects of intra-medial septum injections of L-arginine, a precursor of nitric oxide, N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, and sulpiride, a selective antagonist of dopamine D2 receptor on morphine-induced conditioned place preference (CPP) in male Wistar rats were examined. Using a 3-day schedule of conditioning, morphine (0.5-7.5 mg/kg, s.c.) produced a significant place preference in a dose-dependent manner. The maximum response was observed with 5.0 mg/kg of opioid. Sulpiride (0.3, 1.0 and 3.0 microg/rat), but not L-arginine (0.3, 1.0 and 3.0 microg/rat) or L-NAME (0.3, 1.0 and 3.0 microg/rat), in combination with morphine (5.0 mg/kg), during conditioning, significantly altered morphine-induced CPP. Single doses (0.3, 1.0 and 3.0 microg/rat) of either L-arginine or L-NAME, during conditioning, did not induce CPP. Sulpiride at 0.3-3.0 microg/rat, intra-medial septum, during conditioning, produced a significant conditioned place aversion. Intra-medial septum injections of L-arginine but not L-NAME or sulpiride, 1-2 min before testing, increased the expression of morphine-induced CPP. The administration of sulpiride (0.3, 1.0 and 3.0 microg/rat), but not L-NAME (0.3, 1.0 and 3.0 microg/rat), 1-2 min before the injection of L-arginine (0.3 microg/rat) on day of test, significantly attenuated the response to L-arginine. L-Arginine (0.3-3.0 microg/rat), during conditioning, showed a statistically significant increase in locomotor activity compared with that to control group. Moreover, sulpiride decreased locomotion by itself or in combination with morphine during conditioning and on the test day of morphine CPP. It can be concluded that L-arginine, a precursor of nitric oxide, in the rat median septum may play a role in expression of morphine conditioning due to dopamine release in this area.     

Rationale and design of the ViCTORY (Validation of an Intracycle CT Motion CORrection Algorithm for Diagnostic AccuracY) trial

BackgroundCoronary CT angiography (CTA) has emerged as an effective noninvasive method for direct visualization of the coronary arteries, with high diagnostic performance compared with invasive coronary angiography (ICA). However, coronary CTA is prone to artifacts, including coronary motion, which may reduce its diagnostic performance. Intracycle motion compensation algorithms (MCAs) from a combination of software and hardware techniques now allow for correction of coronary motion, but the diagnostic performance of MCAs compared with traditional coronary CTA reconstruction methods remains unexplored.MethodsViCTORY (Validation of an Intracycle CT Motion CORrection Algorithm for Diagnostic AccuracY) is a prospective international multicenter trial of 218 patients which is designed to evaluate the performance of MCAs for the diagnosis of anatomically obstructive coronary artery disease (CAD) compared with an ICA reference standard, on a per-patient, per-vessel, and per-segment basis. Patients enrolled into ViCTORY will undergo investigational coronary CTA and clinically indicated ICA and will not receive heart rate-lowering medications before coronary CTA. Coronary CTA images will be reconstructed by conventional standard methods as well as by MCAs. Blinded core laboratory interpretation will be performed for coronary CTA and ICA in an intent-to-diagnose fashion.ResultsThe primary end point of ViCTORY is the per-patient diagnostic accuracy of MCAs for the diagnosis of anatomically obstructive CAD compared with ICA. Secondary end points will include other per-patient, per-vessel, and per-segment diagnostic performance characteristics, including accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. Other key secondary end points will include diagnostic interpretability, image quality, the upper heart rate threshold of utility of MCAs, and the additive value of MCAs to traditionally reconstructed coronary CTA.ConclusionViCTORY will determine whether MCAs improve the diagnosis of obstructive CAD in patients undergoing coronary CTA who are not receiving heart rate-lowering medications.     

Biotin/Folate‐decorated Human Serum Albumin Nanoparticles of Docetaxel: Comparison of Chemically Conjugated Nanostructures and Physically Loaded Nanoparticles for Targeting of Breast Cancer

Docetaxel (DTX) is a widely used chemotherapeutic agent with very low water solubility. Conjugation of DTX to human serum albumin (HSA) is an effective way to increase its water solubility. Attachment of folic acid (FA) or biotin as targeting moieties to DTX‐HSA conjugates may lead to active targeting and specific uptake by cancer cells with overexpressed FA or biotin receptors. In this study, FA or biotin molecules were attached to DTX‐HSA conjugates by two different methods. In one method, FA or biotin molecules were attached to remaining NH₂ residues of HSA in DTX‐HSA conjugate by covalent bonds. In the second method, HSA‐FA or HSA‐biotin conjugates were synthesized separately and then combined by DTX‐HSA conjugate in proper ratio to prepare nanoparticles containing DTX‐HSA plus HSA‐FA or HSA‐biotin. Cell viability of different nanoparticle was evaluated on MDA‐MB‐231 (folate receptor positive), A549 (folate receptor negative), and 4T1 (biotin receptor positive) and showed superior cytotoxicity compared with free docetaxel (Taxotere^®). In vivo studies of DTX‐HSA‐FA and DTX‐HSA‐biotin conjugates in BULB/c mice, tumorized by 4T1 cell line, showed the conjugates prepared in this study were more powerful in the reduction in tumor size and increasing the survival rate when compared to free docetaxel.     

The effect of coenzyme Q10 supplementation on partner pregnancy rate in infertile men with idiopathic oligoasthenoteratozoospermia: an open-label prospective study

Objective

It has been shown that coenzyme Q₁₀ (CoQ₁₀) supplementation in men with idiopathic oligoasthenoteratozoospermia (OAT) results in improved semen parameters. In present study, we evaluated the effects of coenzyme CoQ₁₀ supplementation on semen parameters and pregnancy rates in infertile men with idiopathic OAT.

Patients and methods

Two hundred and eighty-seven infertile men with idiopathic OAT were recruited in this study. These patients were treated with CoQ₁₀ 300?mg orally twice daily for 12?months. Two semen analyses and determination of resting levels of sex hormones were done in all participants. Patients were followed up for another 12?months after CoQ₁₀ discontinuation.

Results

Mean sperm concentration, sperm progressive motility, and sperm with normal morphology improved significantly after 12-month CoQ₁₀ therapy by 113.7, 104.8, and 78.9%, respectively (all Ps?< 0.05). The overall pregnancy rate was 34.1% within a mean of 8.4?±?4.7?months.

Conclusions

CoQ₁₀ supplementation improves semen quality with beneficial effect on pregnancy rate.     

Mitochondrial DNA A4336G mutation in Alzheimer's and Parkinson's diseases

OBJECTIVES: To determine whether the mitochondrial DNA (mtDNA) A4336G mutation represents a risk factor for Spanish patients with both Alzheimer's disease (AD) and Parkinson's disease (PD). MATERIAL AND METHODS: One hundred and sixty-one AD and 106 PD unrelated patients were included in the study. Seventy-eight age-matched and 144 randomly chosen healthy subjects served as controls. The frequency of the A4336G mutation in these groups was compared using the chi(2) and Fisher's exact tests. p < 0.05 was established as a statistically significant differential value. RESULTS: The mtDNA A4336G mutation was present in 1/161 of AD patients (0.6%), in 3/106 of PD patients (2.8%), in 1/78 of age-matched controls (1.3%) and in 2/144 of the randomly chosen controls (1.4%). These differences were not statistically significant. CONCLUSION: Our results do not support the hypothesis that this mutation represents a risk factor for either AD or PD patients, at least in the case of this Spanish sample.     

Association of toxicochemical and microbiological quality of bottled mineral water in Birjand city,Iran

Water is one of the pivotal, both in natural ecosystems and human development. Inadequate and unsafe water is still one of the major challenges in most developing countries. Due to the growing trends of bottled water (BW) consumption in Iran, especially in dry regions, regular monitoring of the quality of bottled mineral water is necessary. Therefore, this cross-sectional study was carried out to evaluate the chemical and microbiological quality of bottled mineral water which was sold in the markets of Birjand city, Iran in 2015. Samples were selected randomly from 12 most popular brands of national BW in autumn and winter. Then, 12 most popular brands were selected for analysis. Finally, parameters including total hardness, levels of calcium, magnesium, pH, bicarbonate, sulfate, alkalinity, residual chlorine and total and fecal coliforms were examined for each brand. The results of the present study revealed that most of the chemical and microbiological parameters of BW in Birjand city were lower than maximum contaminant levels which are set by Iranian mineral water quality standards and WHO guidelines. Furthermore, total and fecal coliforms were within the standards. Overall, the results of this study revealed that the health status of the bottled mineral water which is sold in the markets of Birjand city was good. But, regular monitoring of the above mentioned parameters would be helpful to improve the water quality and to provide good portable water for the dwellers and very effective to enhance public health on citizens.     

Effects of general anaesthetic procedures on mitochondrial function of human skeletal muscle

Background: General anaesthetics inhibit mitochondrial function in animal models. However, very few studies have been performed in humans, and the results have not been conclusive. Methods: We prospectively studied the oxygen consumption and the individual enzyme activity of each complex of the mitochondrial respiratory chain of skeletal muscle mitochondria in 54 healthy individuals who underwent general anaesthesia for orthopaedic surgery. The control group (n = 54) was made up of individuals submitted to the same orthopaedic procedure under regional anaesthesia (n = 31), and patients who underwent muscle biopsies for diagnostic purposes by local anaesthesia (n = 23). Results: We found a significant decrease in the oxidation of glutamate (−36%), succinate (−25%) and ascorbate (−29%) in the general anaesthetic group compared with the controls (P < 0.001 for all substrates). The level of such inhibition was similar for volatile anaesthetics with strong (halothane) or weak (isoflurane) negative inotropic effect. By contrast, the enzymatic activity of all individual complexes and the coupling of oxidative phosphorylation did not differ between the two groups. Conclusion: We conclude that during general anaesthetic procedures there is an extensive inhibition of substrate oxidation in human muscle mitochondria, and that it is not caused by a direct effect on complexes of the mitochondrial respiratory chain or through uncoupling oxidative phosphorylation. Received: 27 July 1998 / Accepted in revised form: 27 October 1998