Benefits of a school-based asthma treatment program in the absence of secondhand smoke exposure: results of a randomized clinical trial

BACKGROUND: Daily maintenance medications are recommended for all children with mild persistent to severe persistent asthma; however, poor adherence to these medications is common. OBJECTIVE: To evaluate the impact of school-based provision of inhaled corticosteroids on asthma severity among urban children with mild persistent to severe persistent asthma. DESIGN: Children aged 3 to 7 years with mild persistent to severe persistent asthma were identified at the start of the 2000-2001 and 2001-2002 school years in Rochester. Children were assigned randomly to a school-based care group (daily inhaled corticosteroids provided through the school) or a usual-care group (inhaled corticosteroids not given through school). MAIN OUTCOME MEASURE: Improvement in parent-reported symptom-free days. RESULTS: Of 242 eligible children, 184 were enrolled from 54 urban schools. Data for 180 children were available. Parents of children in the school-based care group had a greater improvement in quality of life compared with parents of children in the usual-care group (change score, 0.63 vs 0.24; P =.047); also, children in the school-based care group vs the usual-care group missed less school because of asthma (mean total days missed, 6.8 vs 8.8; P =.047) and experienced more symptom-free days during the early winter months (mean days per 2-week period, 9.2 vs 7.3; P =.02). A post hoc analysis revealed that all significant findings were produced by differences among children who were not exposed to secondhand smoke. Furthermore, among children not exposed to smoke, those in the school-based care group vs the usual-care group had more symptom-free days overall (11.5 vs 10.5; P =.046), had fewer days needing rescue medications (1.6 vs 2.3; P =.03), and were less likely to have had 3 or more acute visits for asthma (6 [13%] of 47 children vs 17 [31%] of 54 children; P =.03). CONCLUSIONS: School-based provision of inhaled corticosteroids significantly improved symptoms, quality of life, and absenteeism among urban children with mild persistent to severe persistent asthma. This effect was seen only among children not exposed to secondhand smoke.     

Single and multiple exposure tolerance study of polystyrene sulfonate gel: a phase I safety and colposcopy study

OBJECTIVES: To evaluate symptoms and signs of genital irritation, vaginal leakage and acceptability of polystyrene sulfonate (PSS), which is being studied as a vaginal contraceptive and microbicide. METHODS: Forty-nine women applied 2.5 mL of either 5% PSS, 10% PSS, PSS vehicle, or Conceptrol (a marketed spermicidal product containing 4% nonoxynol-9) for 6 consecutive days. RESULTS: All women completed the study except one in the Conceptrol group who experienced vaginal symptoms after her first use and was discontinued. After both the first use and after all uses, irritation was seen among more women in the Conceptrol group than in the PSS groups, reaching statistical significance with regard to any evidence of irritation, signs of irritation and product-related irritation. There were no adverse events that were serious, unexpected and related to product use in any group. The 5% concentration of PSS may be preferable in terms of leakage and acceptability. CONCLUSION: The results suggest that PSS has a safety profile comparable to that of the marketed nonoxynol-9 product, Conceptrol, and appears to be associated with less genital irritation.     

Male tolerance study of 1% C31G

BACKGROUND: C31G is being studied as a vaginal contraceptive and microbicide. This study was conducted to ensure that male partners of the women in future trials of C31G will not be subjected to an undue risk of penile irritation. METHODS: This was a randomized, double-blinded, single-center Phase I study in circumcised and uncircumcised men to assess penile irritation, safety and acceptability of seven consecutive daily doses of 1.0% C31G compared with a marketed spermicide, Extra Strength Gynol II(R) (3% nonoxynol-9) (ES Gynol II). Each participant was instructed to apply the study product to his penis at bedtime, to wash it off 6-10 h later, and to record any symptoms on a diary card. At the follow-up visit, a genital examination was performed and participants were again asked about adverse events and to complete an acceptability questionnaire. RESULTS: Of the 36 men enrolled, 12.5% of C31G users and 16.7% of Extra Strength Gynol II users reported product-related adverse events (AEs). All product-related AEs were considered mild by the investigator, except for one in the ES Gynol II group. Both products were acceptable. CONCLUSION: The manner in which the products were used in this study is not the route by which men will be exposed to such products in actual use, and results should be considered in this light. Based on the observations in this study, C31G appears to be at least as safe and acceptable for male penile exposure as the marketed product ES Gynol II.     

The role of the endosomal/lysosomal system in amyloid-beta production and the pathophysiology of Alzheimer's disease: reexamining the spatial paradox from a lysosomal perspective

One of the hallmarks of Alzheimer's disease is the cerebral deposition of plaques composed of a 37-43 amino acid amyloid-beta (Abeta) peptide. Abeta is produced by the sequential proteolytic cleavage of an integral-membrane protein, amyloid beta-protein precursor (AbetaPP), first by beta-secretase (BACE), and then by gamma-secretase, a complex containing presenilin and Nicastrin. Although these cleavages were originally documented to occur in the endosomal/ lysosomal system, other lines of evidence suggest that the responsible proteins and activity reside in the ER or Golgi. This lack of intracellular co-localization of enzyme and substrate has been referred to as the spatial paradox of Alzheimer's disease. Here we will review the biology of the lysosome and the literature supporting the endosomal/ lysosomal production of Abeta. We will also examine some of the data supporting Abeta production in the biosynthetic compartments and demonstrate its compatibility with an endosomal/ lysosomal model. Finally, we will discuss the possible role of the acidic environment of the lysosome in the amyloidogenic process, and review the evidence for intracellular amyloidogenesis preceding amyloid plaque formation.     

Tacrolimus toxicity associated with concomitant metoclopramide therapy

Subtherapeutic tacrolimus trough concentrations were noted in a 52-year-old woman who had undergone liver transplantation. Her tacrolimus dosage was increased from 7 to 28 mg twice/day, and ketoconazole therapy was added; however, her tacrolimus concentration remained undetectable. Metoclopramide 10 mg 4 times/day was begun to control the patient's new-onset nausea and vomiting. Within 48 hours of increasing the dosage to 20 mg 4 times/day, her tacrolimus trough concentration exceeded 30 ng/ml. Signs and symptoms were suggestive of tacrolimus nephrotoxicity and neurotoxicity. According to the Naranjo scale, this adverse drug event was probably the result of improved absorption of tacrolimus secondary to metoclopramide therapy. The patient's subtherapeutic tacrolimus concentration at baseline was probably secondary to poor absorption due to impaired gastric emptying. Coadministration of metoclopramide significantly improved gastric motility and delivery of tacrolimus to the small intestine, increasing tacrolimus bioavailability, thus resulting in acute-onset tacrolimus toxicity. When tacrolimus is administered with metoclopramide in patients with gastric dysmotility, tacrolimus concentrations should be monitored closely to minimize the risk of toxicity.     

Physician-elder interaction in community family practice

OBJECTIVE: To determine whether outpatient visits by elders seeing community family physicians differ in length or content from visits by younger patients; socioemotional preferences predict visit content; and satisfaction correlates with visit content differentially across age. METHODS: In a multimethod cross-sectional study of 84 community family practices in northeastern Ohio, 3453 adult patient visits with 138 community family physicians were observed; 2362 of these patients completed self-report questionnaires. Three age groups were compared: 18 to 64, 65 to 74, and over 74 years. Length and content of the physician-patient encounter was determined using the Davis Observation Code (DOC); satisfaction was assessed using the MOS 9-item Visit Rating Scale. RESULTS: Controlling for reason for visit and demographics, visit length averaged 10.7 minutes for each group. Visit content differed significantly on 13 of 20 DOC codes between one of the older groups and the younger group; in 4 instances, content varied between the 2 older groups. Although visit content varied as predicted by socioemotional theory, no consistent patterns of association between visit content and satisfaction emerged. DISCUSSION: Older patient visits differ from those of younger patients as might be predicted by socioemotional selectivity theory; however, there was little association of visit content with patient satisfaction.