Pathophysiology and pharmacology of migraine. Is there a place for antiemetics in future treatment strategies?

This article reviews the pathophysiology and pharmacology of emesis in relation to migraine pathogenesis. Also, the place of antiemetic and gastrointestinal prokinetic agents in current and future acute migraine treatment strategies is reviewed. The mechanisms of action of current and novel acute migraine therapies are considered with respect to the neurogenic and vascular hypotheses. Control of migraine-associated nausea and vomiting is often achieved with the benzamide dopamine D₂ receptor antagonist metoclopramide. This drug also has 5HT₃ receptor antagonist activity and reproducibly stimulates gastric motility to increase the availability of orally administered drugs. Other antiemetic and gastroprokinetic agents with potential value for the treatment of migraine-associated nausea and vomiting could speed absorption of oral antimigraine therapies without central nervous system side effects. Domperidone, a dopamine D₂ receptor antagonist that does not cross the blood brain barrier is relatively free of the central side-effect liability of metoclopramide. Cisapride, a benzamide 5HT₄ receptor agonist gastrointestinal prokinetic drug, lacks dopamine antagonist activity. A controlled comparison of these agents as migraine co-therapies could provide information on the importance of peripheral and central mechanisms in migraine-associated nausea and vomiting and improve antimigraine treatment options.     

美国国家骨髓库无关供者造血干细胞移植20年回顾

自美国国家骨髓库(NMDP)开展第一例无关供者移植以来,至今已有20年.NMDP目前的库容量已逾700万,已为6大洲提供了30 000多份无关供者造血干细胞.这一辉煌成就是美国国家骨髓库600多名工作人员共同努力的结果,同时也得益于广泛的国际合作,包括171个移植中心,73个供者中心,24个脐血库,97个骨髓采集中心,91个血液净化中心,26个HLA分型实验室和26个合作供者登记处.本文回顾了美国国家骨髓库的历史,阐述了20年来移植病人、移植物来源和预处理方案几方面的主要变化趋势.     

Detection of antibodies to Trypanosoma cruzi among blood donors in the southwestern and western United States. II. Evaluation of a supplemental enzyme immunoassay and radioimmunoprecipitation assay for confirmation of seroreactivity

BACKGROUND: Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, is endemic to Latin America and may be transmitted in the United States via blood donated by infected immigrants. Blood- borne pathogens such as T. cruzi require supplemental testing for confirmation of seroreactivity. STUDY DESIGN AND METHODS: A study was undertaken to determine an optimal scheme for confirmation of seroreactivity in repeatedly reactive samples identified by the Chagas antibody enzyme immunoassay (EIA). The procedure for initial confirmation involves three purified antigens coated onto three separate polystyrene beads and uses an EIA format. If the sample is reactive with two of three or three of three antigens, it is confirmed as seroreactive. If none or one of three beads is reactive, the sample is indeterminate and subjected to a radioimmunoprecipitation assay (RIPA). The RIPA must demonstrate characteristic bands at 32, 34, and 90 kDa. RESULTS: When tested with sera from persons with potentially cross-reactive diseases (n = 39) or against a presumed negative population from southeast Wisconsin (n = 289), the confirmatory EIA had a specificity of 100 percent. Sensitivity was 100 percent (28/28) with xenodiagnosis-positive sera and 97.6 percent (80/82) with chagasic sera from Latin America. The RIPA showed a specificity of 100 percent in EIA- nonreactive samples (n = 100) and a sensitivity of 100 percent with both xenodiagnosis-positive (28/28) and chagasic (82/82) sera. CONCLUSION: The confirmatory EIA and the RIPA together provide a highly specific and sensitive means of confirming seroreactivity for antibodies to T. cruzi.     

Utilization of supplemental iron by premature infants fed fortified human milk

We measured red blood cell iron incorporation (RBC-inc) in 13 human milk-fed premature infants (birthweight 1037 +/- 289 g, gestational age 27 +/- 2 wk, weight at start of study 1571 +/- 426 g) who were receiving full tube-feedings of human milk fortified with a commercial human milk fortifier (FortHM). The relative RBC-inc of supplemental iron (2 mg/kg/d of ferrous sulfate) was assessed using 57Fe sulfate mixed directly into a 24-h volume of FortHM, and 54Fe sulfate given as a bolus between two FortHM feedings the next day. RBC-inc was similar between the two methods of supplemental iron administration (4.7 +/- 2.5% vs 4.6 +/- 1.5%, respectively). Although these values are lower than RBC-inc expected from iron native to human milk, the relatively large amount of iron in the supplements contributed most of the iron incorporated into RBC by the infants. There was a significant positive correlation between the reticulocyte count and RBC-inc. As the high nutrient (especially calcium) content of the FortHM did not interfere with iron utilization, adding iron directly to FortHM, or incorporating it into commercial fortifiers, may be a practical method to provide iron to premature infants.     

Influence of clinical status on the association between plasma total and unbound bilirubin and death or adverse neurodevelopmental outcomes in extremely low birth weight infants

Objectives: To assess the influence of clinical status on the association between total plasma bilirubin and unbound bilirubin on death or adverse neurodevelopmental outcomes at 18–22 months corrected age in extremely low birth weight infants. Method: Total plasma bilirubin and unbound bilirubin were measured in 1101 extremely low birth weight infants at 5 ± 1 days of age. Clinical criteria were used to classify infants as clinically stable or unstable. Survivors were examined at 18–22 months corrected age by certified examiners. Outcome variables were death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death prior to follow‐up. For all outcomes, the interaction between bilirubin variables and clinical status was assessed in logistic regression analyses adjusted for multiple risk factors. Results: Regardless of clinical status, an increasing level of unbound bilirubin was associated with higher rates of death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss and death before follow‐up. Total plasma bilirubin values were directly associated with death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death before follow‐up in unstable infants, but not in stable infants. An inverse association between total plasma bilirubin and death or cerebral palsy was found in stable infants. Conclusions: In extremely low birth weight infants, clinical status at 5 days of age affects the association between total plasma bilirubin and death or adverse neurodevelopmental outcomes at 18–22 months of corrected age. An increasing level of UB is associated a higher risk of death or adverse neurodevelopmental outcomes regardless of clinical status. Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants.     

Reaction or infection: topical chloramphenicol treatment

Chloramphenicol is a topical treatment that is used widely, especially in wounds around the eyes. In our practice there have been a number of cases of delayed hypersensitivity to chloramphenicol that has been mismanaged initially as an infective cellulitis. We hope to share some of our experience of this uncommon reaction to highlight the delayed reaction that can occur with topical application of this drug.     

Are quality of family life and disease severity related in childhood atopic dermatitis?

BACKGROUND: Atopic dermatitis (AD) can be traumatizing to family life. Little is known about the relationship between quality of life in AD and disease severity. OBJECTIVE: To document family quality of life and relate this to severity of AD in children, for a 6-month period from a given point in time. STUDY DESIGN: These data are part of a longitudinal study conducted in two parts of the UK to investigate risk factors for AD severity and its impact on quality of life. SUBJECTS: and methods Thetargetedpopulation comprised children with AD aged 5-10 years in a primary-care setting. The general practitioners identified potential subjects and the UK diagnostic criteria for AD were used to verify the diagnosis. Both the children and their parents were interviewed. Eczema severity was assessed using a modified form of the SCORAD (SCORe Atopic Dermatitis) Index (SCORAD-D) from which parents' score of itching and sleep loss were excluded. The quality of family life was quantified by the Dermatitis Family Impact (DFI) questionnaire. These two parameters were evaluated on two occasions 6 months apart. ANALYSIS: Multiple regression analysis was used to investigate the relationship between the quality of family life and the severity of the AD in the children, at a specific point in time and over the following 6-month period. RESULTS: Of the 116 children attending the first visit, mean age 8 years, 106 attended the second visit (91%) and were included in the analysis. Quality of family life was shown to be significantly affected in 48 (45%) cases at the first visit and 38 (36%) cases at the second visit. The initial means of the DFI and SCORAD-D were 2.4 and 8.2, respectively. Six months later the mean final DFI and SCORAD-D were 1.9 and 7.7, respectively. Using multiple regression on the first and second visits, each unit increase in SCORAD-D was associated with 0.21 [95% confidence interval (CI) 0.06-0.37 P = 0.008] and 0.37 (95% CI 0.15-0.59, P = 0.001) units increase in quality of family life, respectively. This relationship remained significant even after adjustment for potential confounders (black skin, social class, sex, child's age, family size and location) each unit increase in SCORAD-D led to a 0.25 unit (95% CI 0.11-0.4, P = 0.001) and 0.23 unit (95% CI 0.05-0.42, P = 0.014) increase in DFI on the first and second visits, respectively. Changes in the DFI scores were significantly related to changes in the SCORAD-D scores (regression coefficient; 0.17 (95% CI 0.06-0.29, P = 0.002). CONCLUSIONS: We show that quality of family life is related to the severity of AD in children. This confirms the importance of parental assessment of the impact of the disease in the management of AD, because the disease affects the entire family. Also, these results show the response of DFI to change predictably with disease severity. This may imply that the DFI questionnaire could be used as an extra measure of outcome in everyday clinical practice as well as in research studies.