Efficacy and safety of once-daily fluticasone furoate nasal spray in children with seasonal allergic rhinitis treated for 2 wk

The objective of this study was to evaluate the efficacy and safety of fluticasone furoate (FF) nasal spray 55 and 110 μg once daily in children with seasonal allergic rhinitis (SAR). Patients (n = 554) received placebo nasal spray or FF, administered using a unique side-actuated device, in a 2-wk, randomized, double-blind study. Symptoms were evaluated by patients using a 4-point categorical scale. Efficacy assessments included reflective and instantaneous total nasal symptom scores (r/iTNSS). Primary analyses were conducted in patients aged 6–11 yr in the intent-to-treat population (ITT); the 2–11 yr group provided supportive analyses. In patients aged 6–11 yr, FF 110 μg once daily significantly improved the daily rTNSS compared with placebo. FF 55 μg once daily was only numerically better for rTNSS and iTNSS. Secondary pre-dose iTNSS and overall response to therapy were significant with FF 110 μg. The significant findings for FF 110 μg were supported by analyses in the entire ITT population of 2–11 yr olds. Both doses of FF were well tolerated. These study results suggest that FF nasal spray administered once daily for 2 wk is well tolerated and effective for the treatment of SAR symptoms in children aged 2–11 yr.     

Mechanism by which peripheral galanin increases acute inflammatory pain

Galanin (GAL) is a neuropeptide involved in pain transmission. Intraplantar GAL at low doses enhances capsaicin (CAP)-induced pain behaviors in rat, suggesting an excitatory role for GAL under acute inflammatory conditions. The mechanisms underlying this pro-nociceptive action have not yet been elucidated. Thus, the present study investigated the role of protein kinase C (PKC) in the GAL enhancement of CAP-induced inflammatory pain. Ipsilateral, but not contralateral, calphostin C, a PKC inhibitor, blocked GAL-induced potentiation of CAP-evoked inflammatory pain in a dose-dependent fashion. Peripheral activation of PKC using the phorbol ester phorbol-12-myristate-13-acetate (PMA) mimicked the pro-nociceptive effect of GAL. These results suggest that GAL enhances acute inflammatory pain through activation of PKC intracellular pathways.     

Concurrent chemoradiotherapy with new platinum compound nedaplatin in oral cancer

Eleven patients with oral cancer were treated with the new platinum agent, nedaplatin, and 5-fluorouracil and simultaneous radiation therapy. The regimen was of 5 days' duration: 5-fluorouracil 400-500 mg/m(2) (days 1-5), nedaplatin 80-90 mg/m(2) (day 4), and a total radiation dose of 8-10 Gy (days 1-5). Of the 11 patients, 4 (36.4%) showed complete response and 5 (45.4%) showed partial response; the total response rate was 81.8%. Major side effects were hypochromia (27%), leukopenia (64%), granulocytopenia (55%), thrombocytopenia (36%), nausea and vomiting (82%), and mucositis (45%). Toxicity was grade 2 or less in most of the 11 patients. The results indicate that the regimen composed of combination chemotherapy with nedaplatin and radiation therapy is effective in the treatment of patients with squamous cell carcinoma of the oral region.     

Glu274Lys/Gly309Arg Mutation of the Tissue-Nonspecific Alkaline Phosphatase Gene in Neonatal Hypophosphatasia Associated with Convulsions

We describe a patient diagnosed with lethal perinatal hypophosphatasia with a unique clinical presentation of convulsions that responded to vitamin B₆. Genomic DNA sequence analysis of the tissue-nonspecific alkaline phosphatase (TNSALP) gene revealed two missense mutations: a G-to-A transition resulting in a Glu to Lys at codon 274 (E274K), and a G-to-C transversion resulting in a Gly to Arg at codon 309 (G309R). The first mutation was maternally transmitted and was previously characterized as a moderate one, whereas the latter was paternally transmitted and has not been previously reported. Phenotype/genotype correlation indicates that G309R is a deleterious mutation that can lead to seizures and a lethal outcome, as was demonstrated in our patient.     

Omalizumab, an anti-IgE antibody, in the treatment of adults and adolescents with perennial allergic rhinitis.

BACKGROUND: Treatment with omalizumab, an anti-IgE antibody, improves symptoms and quality of life in patients with seasonal allergic rhinitis but has not previously been investigated in patients with perennial symptoms. OBJECTIVE: To investigate the efficacy, safety, and tolerability of omalizumab in the treatment of perennial allergic rhinitis (PAR). METHODS: Two hundred eighty-nine patients (aged 12 to 70 years) with moderate-to-severe symptomatic PAR were randomized to 16 weeks' double-blind subcutaneous treatment with either placebo (n = 145) or omalizumab (at least 0.016 mg/kg/IgE [IU/mL] per 4 weeks; n = 144). The primary efficacy variable was the mean daily nasal severity score, as determined from patient daily diary cards. Secondary efficacy variables included use of rescue antihistamine, rhinoconjunctivitis-specific quality of life (RQoL), and patients' evaluation of treatment efficacy. Safety and tolerability were evaluated from adverse event reports and laboratory safety parameters. RESULTS: Throughout 16 weeks of treatment, the mean daily nasal severity score was significantly lower in omalizumab-treated patients than with placebo (P < 0.001). The improvement in symptoms when taking omalizumab was paralleled by a reduction in use of rescue antihistamine (P < or = 0.005 overall) and improved RQoL relative to placebo. Patients' evaluation of treatment efficacy significantly favored omalizumab over placebo (P = 0.001). Omalizumab therapy was well tolerated. There were no safety concerns. CONCLUSIONS: Omalizumab was safe and well tolerated in the treatment of patients with PAR, providing effective control of symptoms and improved RQoL while simultaneously minimizing reliance on rescue antihistamines.     

Time-dependent diuretic response in rats treated with Juniper berry preparations

The infusion and the essential oil of juniper berries (Juniperus communis L.) as well as terpinen-4-ol were tested for diuresis response in rats. GC analysis of the oil obtained from the drug sample revealed that the ratio between the pinene fraction and terpinen-4-ol was 5:1. In a 1 day experiment the effect of diuresis reduction was observed and compared with the effect of vasopressin (ADH). The effect of the smallest dose of ADH (0.004 IU/100 g b.w.) intraperitoneally administered was comparable to the effect of a 10% drug infusion and 0.1% essential oil solution, while the effect of 0.4 IU/100 g b.w. of ADH was comparable to that of a 0.01% solution of terpinen-4-ol. During a 3 day experiment diuresis was stimulated after the second application and especially after the third application of test solutions. Among tested preparations a 10% drug infusion exerted the most considerable diuretic activity. After 72 h, i.e. three oral doses of 5 mL/100 g b.w. of drug infusion, the cumulative urine volume was 44% above the control value. The results suggest that the diuretic activity of juniper berries cannot be attributed only to the essential oil but also to hydrophilic drug constituents. Copyright © 1998 John Wiley & Sons, Ltd.     

Serum amyloid A: an early and accurate marker of neonatal early-onset sepsis.

OBJECTIVES: To evaluate the accuracy of serum amyloid A (SAA), an acute phase protein in the detection of neonatal early-onset sepsis, by means of a fast automated SAA kit. STUDY DESIGN: Full-term infants <72 h of age, who had risk factors and/or were suspected of having sepsis, were eligible for study. The levels of SAA were taken at 0, 24 and 48 h post sepsis evaluation. Thirty matched infants served as a control group for comparing SAA concentrations. RESULTS: Of 104 infants eligible for entry to the study, 23 had sepsis and 81 had not sepsis. The SAA levels of the septic group were significantly higher than those of the nonseptic group at 0, 24 and 48 h (P<0.01 for all time points). In comparison with C-reactive protein (CRP), SAA levels rose earlier and in a sharper manner, had higher levels and returned faster to normal values in infants with early onset sepsis. At 0 h post-sepsis evaluation, serum SAA had an overall better diagnostic accuracy for predicting early onset sepsis than CRP (sensitivity (96 vs 30%), specificity (95 vs 98%), positive predictive value (85 vs 78%), negative predictive value (99 vs 83%), positive likelihood ratio (19 vs 12), and negative likelihood ratio (0.05 vs 0.71). CONCLUSIONS: SSA is advocated as an inflammatory marker of neonatal early-onset sepsis.     

Estrogen receptor (ER) gene polymorphism may predict the bone mineral density response to raloxifene in postmenopausal women on chronic hemodialysis

The estrogen receptor (ER) gene has been considered as a candidate genetic marker for osteoporosis, and PvuII and XbaI polymorphisms of the ERalpha gene have been associated with low bone mineral density (BMD). We investigated whether ER polymorphism could predict the response of BMD in 28 postmenopausal women on hemodialysis with marked osteopenia or osteoporosis, randomized to receive raloxifene, a selective estrogen receptor modulator (SERM), or placebo for 1 year. BMD was assessed by dual X-ray absorptiometry and PvuII and XbaI restriction fragment-length polymorphism of the ER gene was determined using polymerase chain reaction. Baseline lumbar spine or femoral neck BMD parameters were not different between patients presenting either homozygous PP or xx when compared with heterozygous Pp or Xx genotypes. After 1 year, patients on raloxifene, presenting with PP or xx genotypes (but not those with Pp or Xx), showed a significantly higher mean lumbar spine BMD (0.942 +/- 0.18 vs. 0.925 +/- 0.17 g/cm2, p < .01) and lower serum pyridinoline (19.7 +/- 9.7 vs. 30.6 +/- 16.5 nmol/L, p < .02) when compared with baseline values. No changes were detected in the placebo-treated patients or in the femur neck sites. In conclusion, after 1 year on raloxifene, postmenopausal osteoporotic women on chronic hemodialysis, homozygous for the P or x (PP or xx) alleles of the ER, exhibited a better lumbar spine BMD response and decreased serum pyridinoline values when compared with heterozygous women (Pp or Xx), suggesting that ERalpha allelic variants may explain, at least in part, the different outcomes after treatment of osteoporosis with SERM.     

Bone turnover markers and bone strength during the first weeks of life in very low birth weight premature infants

OBJECTIVE: To determine the association between changes in bone turnover markers and bone strength of very low birth weight infants during the first eight postnatal weeks. STUDY DESIGN: Twelve very low birth weight premature infants [mean gestational age: 28.4 +/- 0.6 weeks, mean birth weight: 1131 +/- 62 grams] participated in the study. Bone strength was evaluated weekly by quantitative ultrasound measurements of tibial bone speed of sound (SOS, Sunlight Omnisense). Bone specific alkaline phosphatase (BSAP), a marker of bone formation, and carboxy terminal cross-links telopeptide of type-I collagen (ICTP), a marker of bone resorption, were collected at the ages of one, four and eight weeks. RESULTS: BSAP increased significantly (from 119.9 +/- 16.2 U/L to 132.1 +/- 11.9 U/L and 152.1 +/- 15.7 U/L at one, four and eight weeks of life, respectively, p<0.05). ICTP decreased significantly during the study period (from 122.3 +/- 8.7 ng/ml to 96.0 +/- 4.8 ng/ml and 92.3 +/- 5.4 ng/ml at one, four and eight weeks of life, respectively; p<0.05). There was a significant decrease in bone SOS (from 2886 +/- 29 m/sec to 2792 +/- 30 m/sec and 2753 +/- 30 m/sec at birth, four weeks and eight weeks of life, respectively; p<0.02). There was no correlation between the levels of bone markers and bone SOS. CONCLUSION: In VLBW premature infants, there is a significant decrease in bone strength concomitant with biochemical evidence for new bone formation (increase in BSAP and a decrease in ICTP) during the first eight postnatal weeks. Changes in the biochemical markers could not predict the changes in bone strength.     

Antiplasmodial activity of Homalium letestui

The in vivo antiplasmodial activity of the ethanol root extract of Homalium letestui used as a malaria remedy in Southern Nigeria was evaluated in Plasmodium berghei berghei infected mice. Homalium letestui root extract (500-1000 mg/kg/day) exhibited significant (p < 0.05) blood schizontocidal activities both in a 4-day early infection test and in an established infection with a considerable mean survival time comparable to that of the standard drug, chloroquine, 5 mg/kg/day. The root extract possesses significant (p < 0.05) antiplasmodial activity, which can be exploited in malaria therapy.