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Biomedical subjects

F Cox

Publications and source records attributed to F Cox.

At least 19 recordsLinked to original sources

Nocturnal asthma: effect of salmeterol on quality of life and clinical outcomes.

OBJECTIVE: To evaluate the effect of salmeterol on asthma-specific quality of life in patients experiencing significant nocturnal symptoms. DESIGN: Randomized, double-blind, placebo-controlled, multicenter clinical trial. SETTING: Allergy/respiratory care clinics. PATIENTS: Nonsmokers > or = 12 years of age with nocturnal asthma symptoms on at least 6 of 14 days during screening and > or = 15% decrease in peak expiratory flow (PEF) from baseline on nocturnal awakening at least once during screening. INTERVENTIONS: Salmeterol, 42 microg, or placebo twice daily. Patients were allowed to continue theophylline, inhaled corticosteroids, and "as-needed" albuterol. MEASUREMENTS AND RESULTS: Outcome measures included Asthma Quality of Life Questionnaire (AQLQ) global and individual domain scores, FEV1, PEF, nighttime awakenings, asthma symptoms, and supplemental albuterol use. Mean change from baseline for the global and domain AQLQ scores was significantly greater (p < or = 0.005) with salmeterol compared with placebo. At week 12, salmeterol significantly (p < 0.001 compared with placebo) increased mean change from baseline in FEV1, morning and evening PEF, percentage of symptom-free days, percentage of nights with no awakenings due to asthma, and the percentage of days and nights with no supplemental albuterol use. Significant improvements in PEF were observed after treatment with salmeterol regardless of concomitant treatment with theophylline (p < 0.05). CONCLUSIONS: These results provide evidence that validates the role of salmeterol in improving quality of life in patients with moderate persistent asthma who exhibited nocturnal asthma symptoms and supports the efficacy of salmeterol compared with that of placebo (ie, "as-needed" albuterol).

Adolescent

Efficacy, safety, and effects on quality of life of salmeterol versus albuterol in patients with mild to moderate persistent asthma.

BACKGROUND: Salmeterol xinafoate is a long-acting, highly selective, beta2-adrenergic agonist that produces bronchodilation and clinically significant improvement in pulmonary function for up to 12 hours in patients with asthma. OBJECTIVE: To evaluate the impact on asthma-specific quality of life, efficacy, and safety of salmeterol versus albuterol in adult patients with mild-to-moderate persistent asthma. METHODS: A randomized, double-blind, double-dummy, parallel-group, multicenter study was conducted in 539 adult asthma patients over 12 weeks. Patients were randomized to receive either salmeterol 42 microg via metered-dose inhaler twice daily or albuterol 180 microg four times daily. Upon entry into the study, 46% of patients were being treated with an inhaled corticosteroid and were allowed to continue treatment throughout the study. Pulmonary function and asthma symptoms were monitored daily, and patients completed the Asthma Quality of Life Questionnaire (AQLQ) at baseline and after 4, 8, and 12 weeks of treatment. RESULTS: Treatment with salmeterol twice daily produced significantly greater improvements from baseline in all quality of life domain ("Activity Limitation," "Asthma Symptoms," "Emotional Function," "Environmental Exposure") scores and in the global AQLQ score at 12 weeks (P < or = .038) compared with albuterol treatment four times daily. Pulmonary function and asthma symptoms were also significantly improved with salmeterol compared with albuterol. CONCLUSIONS: Salmeterol 42 microg administered twice daily is significantly more effective than albuterol 180 microg four times daily for improving asthma-specific quality of life, controlling asthma symptoms, and improving pulmonary function in patients with mild-to-moderate persistent asthma. Furthermore, those improvements were maintained over a 12-week period.

Adolescent

Ondansetron prevents postoperative emesis in male outpatients. S3A-379 Study Group.

STUDY OBJECTIVES: To determine (1) the efficacy and safety of ondansetron in the prevention of postoperative nausea and vomiting (PONV) in male outpatients; (2) prognostic factors for PONV in male outpatients; and (3) patients' perceptions of the debilitating effects of PONV in the ambulatory surgery setting. DESIGN: Prospective, randomized, stratified, double-blind study. SETTING: Multicenter-24 medical centers. PATIENTS: 468 ASA physical status I and II males at least 12 years of age scheduled for general anesthesia. INTERVENTIONS: All patients received intravenous ondansetron 4 mg or placebo prior to undergoing general balanced (opioid) anesthesia. MEASUREMENTS AND MAIN RESULTS: In the postanesthesia care unit (PACU), the number of emetic episodes, vital signs, adverse events, and nausea assessments were recorded by a blinded observer. After discharge, and until the end of the 24-hour study period, patients completed a diary that collected emetic episodes, adverse events, nausea, and pharmacoeconomic data. There were no differences in patient demographics or safety profiles between groups. The number of patients with no emesis and no nausea during the 24-hour study period was significantly greater (p < 0.05) with ondansetron 4 mg compared with placebo. Prognostic factors for an increased likelihood of developing PONV in males included a history of motion sickness or previous PONV, patients undergoing nonorthopedic procedures, and surgeries lasting longer than one hour. Finally, 38% of patients experiencing PONV perceived PONV to be as, or more debilitating than, the aftereffects of surgery itself. CONCLUSIONS: Ondansetron 4 mg was more effective than placebo in preventing PONV in male outpatients. Males at potential risk for developing PONV include: (1) those with a history of motion sickness and/or PONV; (2) patients undergoing nonorthopedic procedures; and (3) procedures lasting longer than one hour. Such patients may benefit from receipt of a prophylactic antiemetic. Postoperative nausea and vomiting has a debilitating effect that can be differentiated by patients from the effects of surgery itself.

Adult

Prevention of group B streptococcal colonization and bacteremia in neonatal mice with topical vaginal inhibitors.

Pregnant Swiss-Webster mice were vaginally inoculated with 10(5) virulent and avirulent serotype III Streptococcus agalactiae and treated 4 days later with topical vaginal inhibitor solutions. Preparations containing lipoteichoic acid (LTA) or glycerophosphate (GP), the repeating linear backbone of LTA, significantly reduced neonatal colonization and bacteremia by the virulent isolate and colonization by the avirulent strain. Similar results were obtained if bacteria were preincubated with LTA or GP at 37 degrees C for 30 min before vaginal inoculation. Human serum albumin (HSA), a known inhibitor of binding of LTA to human fetal epithelial cells, also resulted in reduction in colonization and bacteremia of neonatal mice. However, maternal treatment with a combination of HSA (2%) and GP (1%) completely prevented neonatal colonization and bacteremia without altering the normal aerobic bacterial vaginal flora. These results provide impetus to the development of an alternative means of preventing neonatal group B streptococcal infections in humans without requiring maternal immunization or chemoprophylaxis.

Animals

Prevention of Escherichia coli K1 bacteremia in newborn mice by using topical vaginal carbohydrates.

Pregnant Swiss-Webster mice were vaginally inoculated with 5 x 10(4) Escherichia coli K1 strain LH (O75:K1:H3) or C94 (O7:K1:H-). Inhibitor solutions were applied vaginally before delivery and the incidence of bacteremia and surface colonization determined in neonates at 3 days of age. E. coli K1 strain LH resulted in bacteremia in 77% and colonization in 74% of control newborn mice. After topical maternal vaginal D-mannose treatment, bacteremia and colonization were present in 25% of neonates. Topical vaginal application of subinhibitory concentration of gentamicin reduced bacteremia to 23% of neonates. Topical methyl-alpha-D-mannoside and p-nitrophenyl-D-mannoside, however, prevented bacteremia in 100% of newborn mice. A neonatal meningitis strain of E. coli K1 (C94) caused bacteremia in 100% of neonates and was also completely inhibited by methyl-alpha-D-mannoside. This technique of vaginal treatment before delivery may have applicability to human mothers and their infants.

Administration, Intravaginal

Identification of a high-virulence clone of serotype III Streptococcus agalactiae by growth characteristics at 40 degrees C.

A high-virulence clone of serotype III Streptococcus agalactiae causing invasive neonatal disease was previously identified by multilocus enzyme electrophoresis. A simple procedure involving growth at 40 degrees C distinguished all isolates classified in this high-virulence clone from other serotype III isolates, which are more frequently associated with asymptomatically colonized infants, as well as the other serotypes of group B streptococci. The high-virulence clone failed to grow at 40 degrees C in FMC, a chemically defined medium, in contrast to the other organisms, which grew readily.

Bacteriological Techniques

Adherence of group B streptococci to buccal epithelial cells in neonates with different gestational ages.

Adherence of group B streptococci to buccal epithelial cells was determined in 81 neonates with different gestational ages. There was a significant curvilinear increase in adherence in premature neonates with decreasing gestational ages. Amniotic fluid did not inhibit attachment of group B streptococci to epithelial cells. Increased adherence of group B streptococci to premature neonates may explain, in part, the increased susceptibility of these infants to disease from this organism.

Adult

Ticarcillin/clavulanic acid combination. Treatment of bacterial infections in hospitalized children.

Eighteen patients 2 months to 11 years of age with culture proven bacterial infections were treated with parenteral ticarcillin/clavulanic acid in a noncomparative study. Seven patients had pneumonia, two had tracheobronchitis, three had soft tissue abscess, two had periorbital cellulitis, three had urinary tract infection and one had purulent bursitis. Four of the 18 were bacteremic. Organisms treated included Staphylococcus aureus (6), Pseudomonas aeruginosa (5), Haemophilus influenzae (2), Branhamella catarrhalis (2), Escherichia coli (1), Streptococcus pneumoniae (1), Klebsiella pneumoniae (1), Streptococcus pyogenes (1) and Serratia marcescens (1). Thirteen of 15 (87%) organisms tested were beta-lactamase positive. Therapy was given intravenously in six doses per day at 310 mg/kg. Duration of treatment ranged from 5 to 28 (mean 11) days, with an average time of 4 days to clinical improvement. Seventeen patients (94%) were clinically cured. One patient with recurrent aspiration pneumonia due to mixed infection with multiple gram-negative enteric bacilli failed therapy. Adverse effects were minimal and transient. Notably, mild to moderate thrombocytosis occurred in four (22%) patients that resolved uneventfully. We conclude that ticarcillin/clavulanic acid is safe and effective therapy for serious infections in hospitalized children.

Bacterial Infections

Molecular cloning of cDNA corresponding to mRNA species whose steady state levels in the thyroid are enhanced by thyrotropin. Homology of one of these sequences with ferritin H.

A lambda gt11 cDNA library was constructed using poly(A)+ mRNA from thyrotropin (TSH)-stimulated Fisher rat thyroid (FRTL5) cells. The library was screened for nonthyroglobulin cDNA sequences by differential plaque filter hybridization using single-stranded cDNA probes synthesized from mRNA prepared from quiescent and TSH-stimulated FRTL5 cells. Thyroglobulin cDNA-containing recombinants in the library were avoided by prehybridizing the TSH probe to excess thyroglobulin cDNA. Of 48,000 clones screened, 60 were chosen as representing mRNA species whose abundance was increased in TSH-stimulated versus quiescent cultures. Southern blot analysis of 9 clones confirmed that the TSH-cDNA probe hybridized to a greater extent to the cDNA inserts than did the control probe. cDNA insert sizes varied between 0.3 kilobase (kb) and 1.0 kb. Northern slot blot analysis using as probes the cDNA of four of these clones (FC4, FC26, FC29, and FC43) demonstrated that TSH stimulation of FRTL5 cells increased the steady state levels of the respective mRNA species by 4-12-fold. For all 4 clones, increases in mRNA levels were apparent within approximately 1 h and were maximal after 14-18 h of TSH stimulation. Determination of the partial nucleotide sequence of these 4 clones confirmed that none was thyroglobulin, thyroid peroxidase, or any other gene previously reported to be stimulated by TSH. Three of the clones bore no homology to any known nucleotide sequence, but FC26 was 85% homologous with human ferritin H. Northern blot analysis using the FC26 cDNA insert as a probe confirmed hybridization to an mRNA species of 1 kb, the known size of ferritin H mRNA. In summary, using the technique of differential plaque filter hybridization, we have identified 4 new genes whose mRNA levels are increased by TSH stimulation of thyroid cells. One of these genes is homologous to human ferritin H.

Animals

IGF-I increases c-fos expression in FRTL5 rat thyroid cells by activating the c-fos promoter.

We studied the effect of IGF-1 on c-fos mRNA expression in FRTL5 rat thyroid cells. IFG-1, or calf serum, transiently increased c-fos mRNA levels in quiescent FRTL5 cells, with the latter being more potent. This increase was prevented by actinomycin D. FRTL5 cells were stably transfected with the c-fos promoter linked upstream to the reporter gene chloramphenicol acetyl transferase (CAT). Calf serum and IGF-1 increased c-fos promoter activity in a prolonged manner, and to an equal degree. Our data indicate that IGF-1, as well as additional factor(s) in serum, increase c-fos mRNA levels, at least in part, by activation of the c-fos promoter.

Animals

Amphotericin B dosage for disseminated candidiasis in premature infants.

Amphotericin B (Amp-B) serum concentrations were determined in five infants with disseminated candidiasis. All patients had positive blood cultures for Candida and one patient had Candida albicans meningitis. Amp-B sterilized the blood and the cerebrospinal fluid within four to nine days. Total doses of Amp-B varied from 11.6-62.3 mg. There was no laboratory or clinical evidence of renal toxicity. Two infants died of causes unrelated to disseminated candidiasis. Disseminated candidiasis in premature infants was treated successfully with 0.5 mg/kg doses of Amp-B, but further studies with more evaluable cases are needed to confirm the correct dose.

Amphotericin B

Lack of toxicity of oral and intrapulmonary group B streptococcal lipoteichoic acid.

Lipoteichoic acid (LTA) was prepared from type III group B streptococci and administered by topical oral application or intravenous or intratracheal injection in weanling and adult white New Zealand rabbits. Tritiated [3H]LTA in tissues and body fluids was measured by scintillation spectrometry. Five minutes to 120 h after intravenous injection of 10 mg (17 x 10(6) dpm) of [3H]LTA, none was present in blood. Combined urine and fecal excretion peaked at 24 h and decreased over 5 days. There was no effect on collagen-induced platelet aggregation. [3H]LTA concentrations were greatest in colon, bone, stomach, and skin 1 day after intravenous injection. After a 5-mg oral dose (8.5 x 10(6) dpm) in an adult animal, fecal excretion peaked at 24 h and decreased after 4 days. No systemic absorption was noted. No [3H]LTA was found in any of seven tissues examined at autopsy 3 days after 1 to 5 mg/kg oral doses in weanling animals with normal or traumatized buccal mucosa. No effect was noted on platelet aggregation or serum complement, there was no increase in the incidence of nephrocalcinosis and the buccal mucosa remained histologically normal. Intratracheal injection of 0.5 to 2.5 mg/kg of LTA resulted in no tachypnea or alteration in blood gases. All animals remained healthy after LTA administration. The absence of toxicity and absorption in animals suggests that studies could be performed in humans to evaluate the safety and efficacy of oral LTA.

Administration, Inhalation

Candida albicans adherence in newborn infants.

Adherence of Candida albicans to buccal epithelial cells from full-term infants was significantly lower than adherence to epithelial cells from premature infants and healthy school-age children, until the full-term infants reached 5 days of age. Adherence in premature infants (gestational age 28-39 weeks) at birth was more than twice that of term infants and remained unchanged during the first week of life. Differences in Candida adherence in premature and term newborns may be due to developmental, salivary, receptor site or other unknown factors.

Adhesiveness