Plasma histamine concentrations in horses administered sodium penicillin, guaifenesin-xylazine-ketamine and isoflurane with morphine or butorphanol.

OBJECTIVE: Various drugs administered to horses undergoing surgical procedures can release histamine. Histamine concentrations were evaluated in horses prepared for surgery and administered butorphanol or morphine intraoperative infusions. STUDY DESIGN: Prospective studies with one randomized. ANIMALS: A total of 44 client-owned horses. METHODS: In one study, anesthesia was induced with xylazine followed by ketamine-diazepam. Anesthesia was maintained with guaifenesin-xylazine-ketamine (GXK) during surgical preparation. For surgery, isoflurane was administered with intravenous (IV) morphine (group M: 0.15 mg kg-1 and 0.1 mg kg-1 hour-1; 15 horses) or butorphanol (group B: 0.05 mg kg-1 and 0.01 mg kg-1 hour-1; 15 horses). Histamine and morphine concentrations were measured using enzyme-linked immunoassay before opioid injection (time 0), and after 1, 2, 5, 30, 60 and 90 minutes. In a subsequent study, plasma histamine concentrations were measured in 14 horses before drug administration (baseline), 15 minutes after IV sodium penicillin and 15 minutes after starting GXK IV infusion. Statistical comparison was performed using anova for repeated measures. Pearson correlation compared morphine and histamine concentrations. Data are presented as mean ± standard deviation. Significance was assumed when p ≤ 0.05. RESULTS: With histamine, differences occurred between baseline (3.2 ± 2.4 ng mL-1) and GXK (5.2 ± 7.1 ng mL-1) and between baseline and time 0 in group B (11.9 ± 13.4 ng mL-1) and group M (11.1 ± 12.4 ng mL-1). No differences occurred between baseline and after penicillin or between groups M and B. Morphine concentrations were higher at 1 minute following injection (8.1 ± 5.1 ng mL-1) than at 30 minutes (4.9 ± 3.1 ng mL-1) and 60 minutes (4.0 ± 2.5 ng mL-1). Histamine correlated with morphine at 2, 30 and 60 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: GXK increased histamine concentration, but concentrations were similar with morphine and butorphanol.

Guaiphenesin-ketamine-xylazine infusion to maintain anesthesia in mules undergoing field castration.

BACKGROUND: In order to determine whether a combination of guaiphenesin, ketamine and xylazine can induce safe and satisfactory anaesthesia in mules undergoing field castration, eight healthy adult intact male mules were employed. They were premedicated with intravenous (IV) xylazine (1.3 mg/kg); an additional dose of xylazine (0.3 mg/kg IV) was administered in case of inadequate depth of sedation. Anaesthesia was induced with IV thiopental (6 mg/kg). The quality of sedation and induction was recorded. Anaesthesia was maintained with an infusion of guaiphenesin (50 mg/mL), ketamine (2 mg/mL) and xylazine (1 mg/mL) (GKX). The spermatic cord of each testis was infiltrated with 5 mL of 2% lidocaine. During anaesthesia heart rate (HR), respiratory rate (RR), rectal temperature (RT) and haemoglobin oxygen saturation (SpO2) were measured every 5 min. The data were analysed with simple one-way analysis of variance (ANOVA). A P value < 0.05 was considered statistically significant. Time of anesthesia, time of surgery and time of recovery were recorded. RESULTS: Only one mule required an additional dose of xylazine to achieve a satisfactory depth of sedation. Thiopental at the dose of 6 mg/kg IV resulted in smooth induction and lateral recumbency in all animals. GKX provided adequate anaesthesia to perform castration in all mules. Muscle relaxation was deemed adequate and physiological variables remained stable and within references values during the anaesthesia and did not change in response to surgical stimulation. Time (mean ± standard deviation) from the end of the infusion to sternal recumbency and time from sternal recumbency to standing were 27.7 ± 4.6 and 30.1 ± 7.7 min, respectively. CONCLUSIONS: The combination of xylazine, thiopental and GKX provides satisfactory short-term anaesthesia in mules undergoing field castration.

The role of mucoactive agents in the mechanically ventilated patient: a review of the literature.

INTRODUCTION: The management of airway secretions in the mechanically ventilated patient is a routine task throughout all intensive care units. The current treatment strategies are primarily based on anecdotal experiences rather than statistical evidence. Areas covered: This review article evaluates the data from published trials surrounding mucoactive agents and their use in the critically ill patient population. We completed an extensive search through PUBMED and CINAHL via EBSCO, along with the Cochran library to find all trials using mucoactive agents in the critically ill patient population. Expert commentary: Overall, the role of mucoactive agents in the intensive care unit is a field within pulmonary critical care that is in need of evidence-based recommendations. We feel that there is great opportunity for investigators to evaluate different mucoactive therapies in this patient population and to determine their effect on clinical outcomes.

Effect of a single 1200 Mg dose of Mucinex® on mucociliary and cough clearance during an acute respiratory tract infection.

BACKGROUND: Observational studies suggest that orally administered guaifenesin (GGE) may thin lower respiratory tract secretions but none have examined its effects on mucociliary and cough clearance (MCC/CC) during a respiratory tract infection (RTI). The current study was a randomized, parallel-group, double-blind, placebo-controlled study in non-smoking adults who suffered from an acute upper RTI. METHODS: We assessed the effects of a single dose of Mucinex(®) 1200 mg (2 × 600 mg extended release tablets) (ER GGE) on 1) MCC/CC by assessing the rate of removal from the lung of inhaled radioactive tracer particles (Tc99m-sulfur colloid), 2) sputum dynamic rheology by stress/strain creep transformation over the linear part of the curve, 3) sessile drop interfacial tension by the deNouy ring technique, and 4) subjective symptom measures. MCC was measured during the morning (period 1) and compared to that in the afternoon 4 h later (period 2) immediately following either drug (n = 19) or placebo (n = 19). For both period 1 and 2 subjects performed 60 voluntary coughs from 60 to 90 min after inhalation of radio-labeled aerosol for a measure of CC. Sputum properties were measured from subjects who expectorated sputum during the cough period post treatment (n = 8-12 for each cohort). RESULTS: We found no effect of ER GGE on MCC or CC compared to placebo. MCC through 60 min for period 1 vs. 2 = 8.3 vs. 11.8% (placebo) and = 9.7 vs. 11.1% (drug) (NS) and CC for period 1 vs. 2 was 9.9 vs. 9.1% (placebo) and 10.8 vs. 5.6% (drug) (NS). There was no significant difference in sputum biophysical properties after administration of drug or placebo. CONCLUSIONS: There was no significant effect of a single dose of ER GGE on MCC/CC or on sputum biophysical properties compared to placebo in this population of adult patients with an acute RTI. ClinicalTrials.gov Identifier: NCT01114581.

Nitric oxide donors improve prednisone effects on muscular dystrophy in the mdx mouse diaphragm.

In Duchenne muscular dystrophy (DMD), palliative glucocorticoid therapy can produce myopathy or calcification. Since increased nitric oxide synthase activity in dystrophic mice promotes regeneration, the outcome of two nitric oxide (NO) donor drugs, MyoNovin (M) and isosorbide dinitrate (I), on the effectiveness of the anti-inflammatory drug prednisone (P) in alleviating progression of dystrophy was tested. Dystrophic mdx mice were treated (18 days) as controls or with an NO donor ± P. Fiber permeability and DNA synthesis were labeled by Evans blue dye (EBD) and bromodeoxyuridine uptake, respectively. P decreased body weight gain, M increased quadriceps mass, and I increased heart mass. P increased fiber permeability (%EBD+ fibers) and calcification in diaphragm. Treatment with NO donors + P (M+P, I+P) reduced %EBD+ fibers and calcification vs. P alone. %EBD+ fibers in M+P diaphragm did not differ from control. NO donor treatment reduced proliferation and the population of c-met+ cells and accelerated fiber regeneration. Concurrent with P, NO donor treatment suppressed two important detrimental effects of P in mice, possibly by accelerating regeneration, rebalancing satellite cell quiescence and activation in dystrophy, and/or increasing perfusion. Results suggest that NO donors could improve current therapy for DMD.

Clinical evaluation of detomidine-butorphanol-guaifenesin-ketamine as short term TIVA in Spiti ponies.

Veterinarians working under remote field conditions are routinely presented with variety of surgical interventions in equines like castrations, management of wound, traumatic and congenital hernias and musculoskeletal disorders thus necessitating the use of general anaesthesia for management of these conditions. The present study was carried out to evaluate and recommend the suitable short term anaesthetic technique for Spiti ponies under field conditions. Seven clinically healthy male Spiti ponies presented for castration were evaluated for short term Total Intravenous Anaesthesia (TIVA) using detomidine (0.02 mg kg(-1)), butorphanol (0.01 mg kg(-1)), 5% guaifenesin (20 mg kg(-1)) and ketamine (2.0 mg kg(-1)). The studies conducted were open label trials and all the animals received same treatment. After proper tetanus prophylaxis and preanesthetic fasting, detomidine was administered intravenously. Subsequently at head down position the animals received butorphanol intravenously. Thereafter, guaifenesin was administered intravenously. As soon as the signs of ataxia developed, the induction of surgical anaesthesia was achieved by intravenous administration of ketamine hydrochloride. The onset of sedation was observed in 2.43 +/- 0.53 min following detomidine administration and the animals were ataxic in 1.43 +/- 0.43 min after butorphanol and guaifenesin administration when ketamine was injected. The ponies were in surgical plane of anaesthesia within 2.28 +/- 0.42 min following ketamine administration. During recovery the limb/head movement and sternal recumbency were attained in 18.71 +/- 1.98 and 26.14 +/- 1.62 min, respectively whereas standing ataxia and normal gait were seen at 29.42 +/- 3.21 and 71.14 +/- 4.74 min, respectively. There was excellent to good muscle relaxation. The surgical anaesthesia remained for 22.57 +/- 1.48 min. The recovery was smooth. Moderate to good suppression of palpebral and corneal reflexes were observed immediately after induction and during anaesthesia. The analgesia was excellent. A highly significant (p < 0.01) to significant (p < 0.05) decrease in respiration rate was observed after induction, during anaesthesia and after recovery. The mean SpO2 value in equines of this group was 76.50 +/- 4.14 and 83.33 +/- 4.18% after induction and during anaesthesia, respectively. Some of the blood biochemical parameters like plasma alanine amino transferase (ALT), total proteins and glucose showed significant increase without clinical consequence. It was concluded that detomidine (0.02 mg kg(-1)), butorphanol (0.01 mg kg(-1)), guaifenesin 5% (20 mg kg(-1)) and ketamine (2.0 mg kg(-1)) combination can safely be used for short term total intravenous anaesthesia in equines under field conditions where the monitoring facilities are meager.

Blockade of MUC1 expression by glycerol guaiacolate inhibits proliferation of human breast cancer cells.

We sought to determine whether administration of glycerol guaiacolate at an optimal biological dose inhibits human breast cancer cell growth. Human breast cancer MCF-7 and ZR-75-1 cells were treated with glycerol guaiacolate and the therapeutic efficacy and biological activity of this drug was investigated on breast cancer cell growth. MCF-7 cells were injected into the mammary fat pad of overectamized female athymic nude mice. Ten days later, animals were treated with daily intraperitoneal injections of glycerol guaiacolate for six weeks. Tumor size and volume was monitored and immunohistochemistry analysis on MUC1, p21 and ki-67 was performed. Glycerol guaiacolate decreased breast cancer cell growth in a dose-dependent manner, decreased cell migration, and caused G1 cell cycle arrest. Our results demonstrate that glycerol guaiacolate inhibits MUC1 protein and mRNA expression levels and significantly increased p21 expression in human breast cancer cells as well as induced PARP cleavage. Similarly, glycerol guaiacolate inhibited breast tumor growth in vivo as well as enhanced p21 expression and decreased breast tumor cell proliferation (ki-67 expression). Collectively, our results demonstrate that glycerol guaiacolate decreased MUC1 expression and enhanced cell growth inhibition by inducing p21 expression in breast cancer cells. These findings suggest that glycerol guaiacolate may provide a novel and effective approach for the treatment of human breast cancer.

Effectiveness of amitriptyline versus cough suppressants in the treatment of chronic cough resulting from postviral vagal neuropathy.

OBJECTIVE: The objective of this prospective, randomized, controlled study (N = 28) was to evaluate the effectiveness of amitriptyline versus cough suppressants in the treatment of chronic cough resulting from postviral vagal neuropathy. METHODS: Patients were selected based on a clinical history consistent with postviral vagal neuropathy and a history of an antecedent upper respiratory tract infection. All patients had been tried on antireflux medication (proton pump inhibitors) and had a negative chest x-ray before presentation. All were nonsmokers without a history of asthma. Patients on angiotensin-converting enzyme inhibitors were excluded from the study. All patients completed a pretreatment, validated cough-specific quality-of-life (QOL) survey. Patients were randomized by chart numbers to either 10 mg amitriptyline at bedtime or 10 to 100 mg/5 mL, 10 mL codeine/guaifenesin every 6 hours standing dose while awake. Both groups were instructed to complete 10 days of therapy and then asked to subjectively rate the reduction in the frequency and severity of their cough by 100%, 75%, 50%, 25%, or 0% as well as completing the posttreatment cough QOL questionnaire. Those patients experiencing a 75% to 100% reduction were recorded as having a complete response, 25% to 50% a partial response, and 0% as having no response. Final results and the cough QOL survey were recorded and used for statistical analysis. RESULTS: A majority of patients in the amitriptyline group achieved a complete response on the initial dose of 10 mg. None of the codeine/guaifenesin group achieved a complete response. The data were analyzed using a logistic regression model, and amitriptyline was found to be a highly significant predictor of a greater than 50% response when compared with codeine/guaifenesin (P = .0007). The same data were analyzed using a proportional odds model and similar results were noted. CONCLUSIONS: Chronic cough can have a profound impact on the psychosocial function of patients. The most common causes of a persisting cough in the absence of infection or chronic smoking are laryngopharyngeal reflux, asthma, particularly the cough variant, allergy, rhinosinusitis, bronchitis, and medications, in particular angiotensin-converting enzyme inhibitors. Currently, there are few effective treatments for cough with an acceptable therapeutic ratio and more selective drugs with a more favorable side effect profile are needed. This is this first prospective, randomized, controlled study comparing the effectiveness of amitriptyline versus codeine/guaifenesin for select cases of chronic cough resulting from suspected postviral vagal neuropathy.

Successful pregnancy despite advanced age and elevated serum follicle stimulating hormone levels--a case report.

PURPOSE: To determine if a woman over age 45 with elevated serum follicle stimulating hormone (FSH) levels in the early follicular phase could still successfully conceive. METHODS: Female partner was treated with guaifenesin to improve cervical mucus quality and vaginal progesterone in the luteal phase. Careful monitoring of follicular maturation was performed. RESULTS: A successful pregnancy after 14 months of progesterone therapy was achieved. CONCLUSIONS: It is possible for a 46-year-old infertile woman with elevated serum FSH to achieve a pregnancy even when the male partner is taking calcium channel blockers for heart problems.

Management of sinusitis in adult cystic fibrosis.

Until recently, cystic fibrosis was frequently fatal during childhood. However, with current medical management, many patients are living into adulthood. This has created a new population of patients with chronic sinusitis and severe medical problems. In this report, experience with 22 patients, eight of whom have undergone sinus surgery, is presented, and recommendations for management are proposed. Presenting symptoms are typical of sinusitis, but in a few patients, severe debilitating headaches predominate. Oral antibiotics are often of little use due to the numerous courses of high dose intravenous antibiotics used for resistant pulmonary infections. Topical nasal steroids and mucolytics have been of some benefit. Fourteen operative procedures were performed on eight patients. These procedures included 12 endoscopic sphenoethmoidectomies, four Caldwell-Luc procedures, two frontal sinus obliterations, and one transseptal sphenoidotomy (many of these were in combination.) Results from this experience indicate 1) Failure of endoscopic surgery to control frontal and maxillary sinus disease; 2) Delayed healing of the ethmoid cavity with persistent crusting; and 3) Significant, albeit short term, symptomatic relief following surgical intervention. Based on this limited series, we conclude that surgery should be delayed until absolutely necessary and that an aggressive approach should be adopted when surgery is performed. In our hands this included initial endoscopic sphenoethmoidectomy with open surgical techniques used for removal of trapped inspissated secretions. We recommend long term intravenous antibiotics postoperatively and frequent cleaning of the ethmoid cavity after surgery, continuing indefinitely, to optimize the benefit of surgery.

Staging of chronic hyperplastic rhinosinusitis: treatment strategies.

In 1990 we reported an initial prospective study of 100 patients using a four-stage system for classification of chronic rhinosinusitis. Between January 1988 and July 1992, we used this system in staging an additional 1814 patients, on whom 2980 intranasal sphenoethmoidectomies were performed. In this staging system a protocol trial of medication was given for 2 weeks, followed by axial and coronal computed tomography. Medication consisted of a second-generation cephalosporin antibiotic, usually cefuroxime; a 4-day burst of intraoral steroids, usually prednisone; and an antihistamine decongestant if not contraindicated. The stages of chronic hyperplastic rhinosinusitis included the stages described in the 1990 report (i.e., stage I, single-focus disease; stage II, discontiguous disease throughout the ethmoid labyrinth; stage III, diffuse disease responsive to medication; and stage IV, diffuse disease unresponsive to or poorly responsive to medication). The results of this study have shown that the computed tomography staging system based on computed tomography extent of disease after medical therapy is a simple, easily remembered, and very effective modality for the classification of chronic sinusitis. This system provides a rationale for discussing and planning surgery with patients and physicians and is a convenient reference for the reporting of end results. More importantly, a linear relationship between disease stage and outcomes is demonstrated. This statistically highly significant feature of the staging system provides a firm basis for the production of outcomes after various treatment strategies, particularly ethmoidectomy and the treatment of sinusitis.

Evaluación clínico-espirométrica comparativa de la combinación ambroxol-clenbuteron vs terbutalina-guaifenesina en pacientes con neumopatía aguda / Clinical-sperometric evaluation comparing ambroxol-clenbuteron vs terbutaline-guaifenesine in patients with pneumopathy

Se efectuó una evaluación clínico-espirométrica comparativa en 30 pacientes con diagnóstico de neumopatía aguda ingresados en el departamento de neumología del Hospital General "Dr. Aurelio Valdivieso" de la S.S.A. en la Ciudad de Oaxaca, Oax., tratados con la asociación medicamentosa ambroxol-clenbuterol y con la asociación terbutalina-guaifenesina. Ambos tratamientos se administraron durante una semana. Se observó claramente una mejoría funcional comparativamente mayor, reflejada en el incremento de los volúmenes pulmonares, en los pacientes tratados con la asociación ambroxol-clenbuterol, por lo que se incluye que dicha asociación ese más benéfica en el tratamiento de este tipo de talología pulmonar.

[The clinical pharmacology of glycerol guaiacolate ether in the horse--a review]. / Die kliniese farmakologie van gliserol guaiakolaat eter in die perd--'n oorsig.

The physical and chemical properties, administration, biotransformation, pharmacological effects, clinical applications, side-effects, toxicity and contraindications of glyceryl guaiacolate ether in the horse are reviewed.

Chronic obstructive pulmonary disease.

The diagnosis of COPD can easily be made on the basis of history, physical findings, and simple laboratory procedures. Treatment is aimed at symptoms and is individualized to the patient's needs. Therapy must be given on a long-term basis. The patient should be educated in the basic nature of his disease and encouraged to return to as normal a life as possible. Patients with COPD often are severely restricted in their earning ability, and treatment can cause a severe financial drain. Thus the physician should carefully consider costs--especially the cost of medications. Finally, the correct choice and use of the many therapeutic measures available can yield marked symptomatic relief and improvement in lifestyle--often allowing the patient to return to productive employment.

[Defence capacities of the respiratory tract]. / Die Abwehrleistungen des Respirationstraktes

The defenses of the lung against inhaled gases and particles include aerodynamic filtration mechanisms of the tracheobronchial tree, mechanical clearance and local detoxification. Cough, mucociliary transport, alveolo-bronchiolar fluid flow and clearance to lymph and blood participate in the mechanical excretory mechanisms whereas phagocytosis, immunologic and secretory mechanisms, and tissue reaction represent in-situ detoxification. Impaired mucociliary transport causes obstruction of the airways, the pathophysiologic hallmark of chronic nonspecific lung diseases. The clearance of diseases airways is not easy. It may be accomplished either by changing primarily the physicochemical properties of the mucus or by stimulating ciliary activity. By means of doublebind-crossover studies in patients with stable chronic nonspecific lung diseases, it is shown how drugs which presumably improve the clearance of diseased airways do affect the various physicochemical properties of the tracheobronchial mucus.