Stanley Goldstein

The addition of salmeterol to fluticasone propionate versus increasing the dose of fluticasone propionate in patients with persistent asthma

BACKGROUND Current treatment guidelines define inhaled corticosteroids such as fluticasone propionate (FP) as the cornerstone of anti-inflammatory therapy for asthma. OBJECTIVE The objective was to evaluate the efficacy and safety of adding salmeterol therapy to patients who remain symptomatic while receiving FP as compared with increasing the dose of FP. METHODS In a multicenter, double-blind study conducted over 24-weeks, 437 patients aged 12 years and older and receiving FP 88 microg twice daily for 2 to 4 weeks were randomly assigned to receive either salmeterol (42 microg twice daily) or FP 220 microg twice daily. The primary efficacy endpoint was morning peak expiratory flow. Secondary measures included FEV1, symptom scores, nighttime awakenings, and supplemental albuterol use. Safety was assessed by reported adverse events and asthma exacerbations. RESULTS The addition of salmeterol resulted in significantly greater improvements in lung function and symptom control as compared with increasing the dose of FP. Over weeks 1 to 24, morning peak expiratory flow was increased by 47 L/min from baseline with salmeterol treatment as compared with 24 L/min with FP 220 microg twice daily (P < .001) while the percent of symptom-free days increased from baseline by 26% of days as compared with 10% of days (P < .001). The adverse event profiles were similar between groups and fewer exacerbations were reported with salmeterol treatment. CONCLUSIONS The addition of salmeterol therapy to patients who remain symptomatic while using a low dose of FP was clinically and statistically superior to increasing the dose of FP.

Critical Issues in Response-To-Intervention, Comprehensive Evaluation, and Specific Learning Disabilities Identification and Intervention: An Expert White Paper Consensus

Developed in concert with the Learning Disabilities Association of America (LDA), this White Paper regarding specific learning disabilities identification and intervention represents the expert consensus of 58 accomplished scholars in education, psychology, medicine, and the law. Survey responses and empirical evidence suggest that five conclusions are warranted: 1) The SLD definition should be maintained and the statutory requirements in SLD identification procedures should be strengthened; 2) neither ability-achievement discrepancy analysis nor failure to respond to intervention alone is sufficient for SLD identification; 3) a “third method” approach that identifies a pattern of psychological processing strengths and weaknesses, and achievement deficits consistent with this pattern of processing weaknesses, makes the most empirical and clinical sense; 4) an empirically-validated RTI model could be used to prevent learning problems, but comprehensive evaluations should occur for SLD identification purposes, and children with SLD need individualized interventions based on specific learning needs, not merely more intense interventions; and 5) assessment of cognitive and neuropsychological processes should be used for both SLD identification and intervention purposes.

Relief of cough and nasal symptoms associated with allergic rhinitis by mometasone furoate nasal spray

BACKGROUND Cough commonly occurs as a symptom of seasonal allergic rhinitis (SAR), an inflammatory condition of the nasal mucous membranes that results in rhinorrhea, nasal stuffiness/congestion, nasal itching, and sneezing. Mometasone furoate nasal spray (MFNS, Nasonex, Schering, Kenilworth, NJ), an anti-inflammatory nasal corticosteroid, has been shown to be safe and effective in reducing the nasal inflammation of SAR. OBJECTIVE To examine the effectiveness of MFNS in relieving SAR-associated cough, in addition to nasal symptoms. METHODS This was a multicenter, randomized, double-blind study. Patients 12 years of age or older with > or = 1-year history of SAR symptoms, positive skin test to a prevailing seasonal allergen, moderate nasal symptoms, and moderate cough were treated for 14 days with MFNS 200 microg daily (n = 122) or placebo (n = 123). RESULTS The group treated with MFNS showed significant improvement in the daytime cough severity score at endpoint compared with placebo (P = 0.049). Improvement in the nighttime cough severity score showed a trend in favor of MFNS treatment. Treatment with MFNS significantly improved total nasal symptoms in both the daytime and nighttime compared with placebo at endpoint (P < or = 0.017). Overall daytime symptom scores (cough + total nasal) improved significantly compared with placebo at endpoint (P = 0.005). Overall nighttime symptom scores improved significantly compared with placebo at endpoint (P = 0.028). Treatments were well tolerated, with no significant differences in the incidence of adverse events. CONCLUSIONS MFNS is effective and well tolerated in the treatment of daytime cough associated with SAR.

Local intranasal immunotherapy for ragweed allergic rhinitis II. Immunologic response

Local nasal immunotherapy (LNIT) was administered in a double-blind study to 67 subjects. Twenty-three received an unmodified ragweed extract (RW), 24 received a glutaraldehyde polymer of ragweed extract (PRW), and 21 received placebo. Serum ragweed-specific IgE (S-IgE), ragweed-specific nasal secretory (NS-) IgE, secretory IgA (SIgA) and IgG, and NS-albumin were measured. RW therapy caused a significant increase in ragweed-specific S-IgE (p less than 0.005) and NS-SIgA (p less than 0.05). PRW therapy caused a significant rise in ragweed-specific NS-SIgA (p less than 0.001). NS-IgE (p less than 0.05), and NS-IgG (p less than 0.01). Ragweed-specific S-IgG was not affected by any of the treatments. There was no consistent correlation between NS-antibody levels and symptom/medication scores.

A novel frameshift mutation of FOXC2 gene in a family with hereditary lymphedema-distichiasis syndrome associated with renal disease and diabetes mellitus.

Lymphedema‐distichiasis (LD) syndrome is a clinically variable autosomal dominant disorder. The disorder is caused by mutations in the forkhead transcription factor FOXC2 gene on chromosome band 16q24.3. Here, we report the sequence of the FOXC2 gene in a German–Irish family with LD in six affected relatives over three generations and identify a single adenine base pair insertion at nt 1006⁁1007. This insertion creates a frameshift mutation that predicts a premature stop at codon 462. In addition to LD, four of the affected family members have renal disease and three have diabetes mellitus (DM), not usually seen in the LD syndrome. Polymorphisms of FOXC2 in diabetics have been studied in different populations. Our sequence analysis of the 5′ untranslated region (UTR) C‐512T shows the homozygous T allele in all family members tested. The sequencing data in this family suggests the possibility of a novel phenotype–haplotype. This novel phenotype, LD/renal disease/type 2 diabetes, might be the result of a combination of the nt 1006⁁1007 insA and the upstream UTR homozygous T polymorphism.

Local nasal immunotherapy for ragweed-allergic rhinitis. III: A second year of treatment

In 1979, pre‐seasonal local nasal immunotherapy (LNIT) was found to be an effective treatment for ragweed hay fever. In 1980. this study was continued to evaluate the clinical and immunologic responses of a second year of LNIT. Patients received either pre‐seasonal treatment with an unmodified ragweed extract (RW) or a polymerized ragweed extract (PRW), or no treatment. The results of the second year of treatment were the same as the first year. Adverse reactions were significantly higher in the RW‐treated group than in the PRW‐treated group (P < 0.001), Symptom/medication scores (SMS) in the RW‐treated group were significantly lower than in the control group (P < 0.005). Although SMS in the PRW‐treated group were lower than in the control group, this difference was not significant. The immunologic response was evaluated by measurements of serum (S) RW‐specific IgE and IgG and nasal secretory (NS) RW‐specific IgE, IgG, and IgA, After treatment, serum IgE titres and secretory IgA titres rose in the RW‐treated patients. Nasal secretory‐IgG and NS‐IgA titres increased with PRW treatment. The only immunologic response observed in the control group was a rise in S‐IgE titres after the ragweed season. There was no substantial difference in immunologic measurements observed in the 1979 and 1980 seasons, except that the pre‐treatment NS‐IgE level was higher in 1980 (P < 0.02). No significant correlations were found between antibody response and SMS. This study supports the efficacy of LNIT but does not support the protective role for NS‐ragweed‐specific IgA or IgG.

Ineffectiveness of imipramine in children who fail to respond to methylphenidate

Ten hyperactive children who had failed to respond to methylphenidate were treated with imipramine in a placebo-controlled, crossover design. No significant drug effects were obtained either on parent and teacher ratings of the childs behavior or on the childs performance in a laboratory measure of sustained attention. Findings suggest that imipramine has limited clinical usefulness in the treatment of hyperactive children who fail to respond to methylphenidate.

Speed of onset of action of Tilarin

Donnelly A., Bernstein D. I., Goldstein S., Grossman J., Schwartz H. J., Casale T. B. Speed of onset of action of Tilarin.

Distichiasis-lymphedema syndrome: Tetralogy of Fallot, chylothorax, and neonatal death

We describe a newborn female with a severe presentation of distichiasis-lymphedema syndrome (McKusick 15340). She was initially evaluated because of a phenotype suggestive of Ullrich-Turner or Noonan syndrome (low posterior hairline, cupped ears, severe pterygium colli, heart murmur, and pectus excavatum). Distichiasis was noted at age 6 weeks. Subsequent to surgery for tetralogy of Fallot, patent ductus arteriosus, and branch pulmonic stenosis, she developed persistent chylothorax and sepsis. She died at 3 months. Family history indicated segregation of distichiasis-lymphedema syndrome. She was the sixth member in her family to have this disorder and was the most severely affected.

Diagnostic value of the first heart sound in children with atrial septal defect

The pre- and postoperative phonocardiograms of 24 children with uncomplicated atrial septal defect (ostium secundum type) were analyzed. The amplitude of the mitral (M1) and tricuspid (T1) components of the first heart sound were measured in each patient at the apex prior to surgery. It was found that in 18 of the 24 children studied (75 per cent) T1 had higher amplitude than M1 at the apex (T1M1 ratio > 1). Three out of 24 children (12.5 per cent) had equal T1 and M1 amplitudes (T1M1 ratio = 1), and 3 (12.5 per cent) had T1 amplitude less than M1 (T1M1 ratio < 1). No positive correlation was found between the T1M1 ratio, and the size of the left to right shunt, mean pulmonary artery pressure, right ventricular hypertrophy, and/or degree of splitting of the first heart sound. After surgery the T1M1 ratio became less than 1 in 22 children and equal to 1 in 2 children. A T1 higher than M1 at the apex is a sensitive index of atrial septal defect since this finding was present even in the presence of a small left to right shunt. Routine phonocardiographic measurement of the amplitude of both components of the first heart sound at the apex is recommended.