Induction of non-specific airway hyperreactivity by potassium channel blockade in rat isolated trachea.

1. The exposure of rat isolated tracheal segment to the K(+)-channel inhibitor tetraethylammonium (TEA, 10 mM) for a period of 10-15 min generally produced little or no contractile response. 2. Cooling (10 C) provocation alone usually produced small (10 +/- 3% acetylcholine maximum) contractile responses. 3. In the presence of TEA (10 mM, 10-15 min exposure), rat trachea exhibited airway hyperreactivity to acetylcholine, 5-hydroxytryptamine (5-HT) and cooling. It also increased the peak tension induced by 5-HT. 4. TEA-induced airway hyperreactivity to cooling was significantly inhibited in Ca2(+)-free Krebs solution suggesting an important role for extracellular Ca2+ influx. 5. We conclude that the blockade of potassium channels with TEA induces non-specific airway hyperreactivity to cooling, 5-HT and acetylcholine in rat isolated tracheal segments.     

Pharmacology of a new non-steroidal anti-inflammatory agent 7-chloro-3,3a-dihydro-2-methyl-2H,9H-isoxazolo-(3,2-b)(1,3)-benzoxazin-9-one (W-2395)

W-2395, a new heterocyclic compound, is an orally effective anti-inflammatory, analgesic and antipyretic agent. It is active in adjuvant-induced polyarthritis when given prophylactically or therapeutically. W-2395 also inhibits carrageenan-induced hind paw edema in the rat, an activity which is not altered by adrenalectomy or hypophysectomy. The analgesic activity of W-2395 is superior to that of acetylsalicylic acid or phenylbutazone, while its antipyretic activity in rats with yeast-induced fever is equivalent to aspirin. Unlike other useful anti-inflammatory agents, W-2395 does not produce ulcers when given in effective doses, nor does it cause gastrointestinal blood loss as measured by the excretion of ⁵¹Cr-tagged red blood cells. However, at lethal doses ulcerogenicity was observed. W-2395 has a weak diuretic effect which most likely does not contribute to its anti-inflammatory action.     

Abdominal scar endometriosis after caesarean section: report of five cases

Scar endometriosis is an under-appreciated or misdiagnosed phenomenon in general surgery and may eventually be more common than reflected in the literature. We herein report five cases of scar endometriosis that were treated in our surgical department one to five years after Caesarean section. Scar endometriosis should be considered when the symptoms are present in a cyclic manner mostly after gynaecological operations and worsening during menstruation. Diagnosis is mainly based upon a high index ofsuspicion. The treatment of choice is surgical resection.     

New Technique for Endoscopic Removal of Intragastric Balloon Placed for Treatment of Morbid Obesity

Background Placement and removal of the intragastric balloon for obesity are performed endoscopically often under general anesthesia. We propose a safer and faster technique for endoscopic removal of the intragastric balloon using standard sedation. Methods In 87 obese patients, we performed 3 removal techniques: 1) standard gastroscope and foreign body forceps, 2) standard gastroscope and retrieval snare, 3) double-channel gastroscope and foreign body forceps plus symmetrical “shark model” polypectomy snare. Balloon retrieval time, number of times the grasping devices lost the balloon, amount of antispasmodic drug, symptoms cumulative score and VAS score for discomfort were evaluated. Results The technique by double-channel gastroscope and foreign body forceps plus symmetrical polypectomy shark retrieval snare showed a significantly lower balloon retrieval time, number of lost balloons, total number of ampoules used, symptoms cumulative score and VAS score compared to the other two techniques (Dunn’s P < 0.05). Number of lost balloons was positively associated with number of antispasmodic ampoules used, balloon retrieval time and VAS score. Conclusions Technique by double-channel gastroscope and foreign body forceps plus symmetrical polypectomy shark retrieval snare, allows balloon removal safely, quickly and easily, avoiding loss of the balloon, with good patient endurance.     

Effect of Diabetes Mellitus on the Clinical and Microbiological Features of Hospitalized Elderly Patients with Acute Pyelonephritis

OBJECTIVES: To study potential differences in the clinical and microbiological features of hospitalized elderly patients with acute pyelonephritis with and without diabetes mellitus.
DESIGN: Retrospective review of medical records.
SETTING: University hospital.
PARTICIPANTS: Eighty-eight patients aged 65 and older with diabetes mellitus (DM) (57 female; 64.8%) and 118 controls without DM (75 female; 63.6%), matched for age and sex, hospitalized with acute pyelonephritis between January 1997 and December 2005.
MEASUREMENTS: Medical records were reviewed for demographic, clinical, and microbiological characteristics.
RESULTS: The median age of both groups was 74 (range 65–95). Twenty-seven people with DM (30.7%) and 13 controls (11.0%) had bacteremia ( P =.001). People with DM had longer fever (median 4.5 vs 2.5 days; P <.001), longer hospitalization (median 10 vs 7 days; P <.001), and greater mortality (12.5% vs 2.5%; P <.01) than controls. Logistic regression analysis proved DM to be an independent predictor of bacteremia, long hospitalization, and mortality. Escherichia coli was the most common microorganism found in both groups, whereas Candida spp. were implicated more frequently in people with DM than controls (12.7% vs 1.7%; P <.01). Antimicrobial resistance did not increase over the study period.
CONCLUSION: Acute pyelonephritis in elderly people with DM is associated with risk of bacteremia, long hospitalization, and mortality.     

Application of a loading dose of colistin methanesulfonate in critically ill patients: population pharmacokinetics, protein binding, and prediction of bacterial kill

A previous pharmacokinetic study on dosing of colistin methanesulfonate (CMS) at 240 mg (3 million units [MU]) every 8 h indicated that colistin has a long half-life, resulting in insufficient concentrations for the first 12 to 48 h after initiation of treatment. A loading dose would therefore be beneficial. The aim of this study was to evaluate CMS and colistin pharmacokinetics following a 480-mg (6-MU) loading dose in critically ill patients and to explore the bacterial kill following the use of different dosing regimens obtained by predictions from a pharmacokinetic-pharmacodynamic model developed from an in vitro study on Pseudomonas aeruginosa. The unbound fractions of colistin A and colistin B were determined using equilibrium dialysis and considered in the predictions. Ten critically ill patients (6 males; mean age, 54 years; mean creatinine clearance, 82 ml/min) with infections caused by multidrug-resistant Gram-negative bacteria were enrolled in the study. The pharmacokinetic data collected after the first and eighth doses were analyzed simultaneously with the data from the previous study (total, 28 patients) in the NONMEM program. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.026 and 2.2 h, respectively. For colistin, a one-compartment model was sufficient and the estimated half-life was 18.5 h. The unbound fractions of colistin in the patients were 26 to 41% at clinical concentrations. Colistin A, but not colistin B, had a concentration-dependent binding. The predictions suggested that the time to 3-log-unit bacterial kill for a 480-mg loading dose was reduced to half of that for the dose of 240 mg.     

Patient preferences on the use of technology in cancer surveillance after curative surgery: A cross-sectional analysis

Background

Advances in communication technology have enabled new methods of delivering test results to cancer survivors. We sought to determine patient preferences regarding the use of newer technology in delivering test results during cancer surveillance.

LINX■ reflux management system to bridge the “treatment gap” in gastroesophageal reflux disease: A systematic review of 35 studies

BACKGROUND Gastroesophageal reflux disease(GERD) occurs when the reflux of stomach contents causes troublesome symptoms and/or complications. When medical therapy is insufficient, surgical therapy is indicated and, until now, Laparoscopic fundoplication(LF) constitutes the gold-standard method. However, magnetic sphincter augmentation(MSA) using the LINX^® Reflux Management System has recently emerged and disputes the standard therapeutic approach.AIM To investigate the device’s safety and efficacy in resolving GERD symptoms.METHODS This is a systematic review conducted in accordance to the PRISMA guidelines.We searched MEDLINE, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL databases from inception until September 2019.RESULTS Overall, 35 studies with a total number of 2511 MSA patients were included and analyzed. Post-operative proton-pump inhibitor(PPI) cessation rates reached 100%, with less bloating symptoms and a better ability to belch or vomit in comparison to LF. Special patient groups(e.g., bariatric or large hiatal-hernias)had promising results too. The most common postoperative complication was dysphagia ranging between 6% and 83%. Dilation due to dysphagia occurred in 8% of patients with typical inclusion criteria. Esophageal erosion may occur in up to 0.03% of patients. Furthermore, a recent trial indicated MSA as an efficient alternative to double-dose PPIs in moderate-to-severe GERD.CONCLUSION The findings of our review suggest that MSA has the potential to bridge the treatment gap between maxed-out medical treatment and LF. However, further studies with longer follow-up are needed for a better elucidation of these results.     

Fatal intoxication with antidepressants: a case with many culprits

Serotonin-specific reuptake inhibitors (SSRIs) are generally considered safe drugs but fatal adverse effects do sometimes occur, often as a consequence of interactions with other serotonin active drugs. Polypharmacy is usually a problem that the elderly encounter, but it can also have dire consequences for young people, especially when an underlying heart condition is present. Thus, failure to diagnose heart disease and the use of contraindicated medications can be a lethal combination, irrespective of age. Here we present a case of a young adult suffering from bipolar disorder who used a combination of two SSRIs (citalopram and fluoxetine) and a monoamine oxidase inhibitor (MAO; moclobemide) with tragic consequences. The deceased also suffered from undiagnosed hypertrophic cardiomyopathy and was carrier of a genotype that may have predisposed him to increased sensitivity to SSRIs. The apparent difficulty in establishing the manner of death in this case is also discussed.