Gastric ulcer disease in infants: US findings

Among 600 infants examined with ultrasound for vomiting, seven (mean age, 3 months) had distinctive features that can be considered diagnostic of gastric ulcer. The findings are thickening of the mucosa (greater than 4 mm) in the antropyloric region, elongation of the antropyloric canal, persistent spasm, and delayed gastric emptying. Two of the infants had slight thickening of the pyloric muscle. Gastrointestinal series or endoscopy demonstrated thickened gastric mucosa and a deformed gastric antrum in all infants, as well as actual ulceration in five.     

The pharmacology of a new pasteurized antihemophilic factor concentrate derived from human blood plasma

The pharmacology of a new pasteurized factor VIII (FVIII) concentrate derived from human blood plasma was studied in 23 adults with hemophilia A. In Part 1 of the study involving six nonbleeding subjects, the mean increase in FVIII activity was 1.43 +/- 0.34 U per ml 10 minutes after an intravenous dose of 50 U per kg. The intravascular survival kinetics in these six patients showed a biphasic decay curve with an initial mean half-life of 5.1 +/- 1.2 hours probably representing early redistribution, and a late half-life of 13.3 +/- 4.9 hours. In Part 2 of the study, the activity at 10 minutes was measured in another 17 patients, as well as in one patient already studied in Part 1. The mean increase in activity with the 24 observations was 1.13 +/- 0.37 U per ml with a mean FVIII dosage of 51.0 +/- 2.6 U per kg of body weight. Only one patient had an allergic reaction, which did not recur when the patient was given a second lot.     

Platelet-activating factor acetylhydrolase is increased in lung lavage fluid from patients with acute respiratory distress syndrome

OBJECTIVE: Platelet-activating factor (PAF) is a proinflammatory phospholipid that may contribute to inflammation in the acute respiratory distress syndrome (ARDS). PAF acetylhydrolase (PAF-AH) degrades PAF and regulates its biological activity. We characterized PAF-AH in bronchoalveolar lavage fluid from ARDS patients (n = 33, 22 survivors), patients at risk for ARDS (n = 6), and healthy controls (n = 6). DESIGN: Bronchoalveolar lavage was performed during acute (<96 hrs from onset), plateau (6 to 12 days), and late (> or = 14 days) phases of ARDS. PATIENTS: Intubated patients with ARDS or a risk factor for ARDS. MEASUREMENTS AND MAIN RESULTS: In ARDS, total bronchoalveolar lavage PAF-AH activity was markedly increased in the acute phase (87 +/- 89 mU/mL, n = 33) and then decreased in the plateau (23 +/- 14 mU/mL, n = 10) and late phases (19 +/- 14 mU/mL, n = 7) (p = .003). Total bronchoalveolar lavage PAF-AH activity during the acute phase of ARDS was also increased as compared with patients at risk for ARDS (16 +/- 13 mU/mL, n = 6) and healthy controls (3 +/- 3 mU/mL, n = 6) (p < .001). In contrast, plasma PAF-AH activities were the same in controls (3215 +/- 858 mU/mL, n = 6), in patients at risk for ARDS (3606 +/- 1607 mU/mL, n = 6), and during the acute phase of ARDS (3098 +/- 2395 mU/mL, n = 33) (p = .18). PAF-AH mRNA was present in alveolar macrophages in the acute phase of ARDS (five of six) and in at-risk patients (two of three) but not in healthy controls. CONCLUSIONS: PAF-AH activity is increased in bronchoalveolar lavage fluid from patients with ARDS. Likely sources include leakage of plasma PAF-AH into alveoli or release of PAF-AH from injured cells; however, the presence of PAF-AH mRNA in alveolar macrophages suggests that PAF-AH may be actively synthesized in the lungs of patients with ARDS. PAF-AH activity in the lungs of ARDS patients may regulate inflammation caused by PAF and related oxidized phospholipids generated in the inflammatory response.     

Pharmacogenetic characterization of indacaterol,a novel β2-adrenoceptor agonist

Background and purpose:

Indacaterol is a novel β₂-adrenoceptor agonist in development for the treatment of chronic obstructive pulmonary disease. The aim of this study was to investigate the comparative pharmacology of indacaterol in recombinant cells expressing the common polymorphic variants of the human β₂-adrenoceptor and in human primary airway smooth muscle (ASM) cells.

Experimental approach:

Chinese hamster ovarian-K1 cell lines expressing high and low levels of the common human β₂-adrenoceptor variants were generated [Gly16-Glu27-Val34-Thr164(GEVT), RQVT, GQVT] and also the rare GQVI variant. Human primary ASM cells were isolated from explants of trachealis muscle. Adenosine-3′,5′-cyclic-monophosphate production was used as an outcome measure.

Key results:

In both the low- and high-expression recombinant GEVT ‘wild type’ cell lines indacaterol is a high-efficacy agonist. Salmeterol and formoterol were identified as low- and high-efficacy agonists, respectively, and showed similar potencies to indacaterol irrespective of the β₂-adrenoceptor genotype. The I164 variant cell line was associated with a reduced capacity to generate adenosine-3′,5′-cyclic-monophosphate in response to β₂-adrenoceptor agonist. In the human primary ASM cells indacaterol gave a maximal response intermediate between that of salmeterol and formoterol.

Conclusions and implications:

These data demonstrate that indacaterol is a high-efficacy agonist in recombinant cell systems but acts with lower efficacy in human primary ASM cells. No marked genotype-dependent effects were observed for common variants; however, changes in I164 receptor activity were identified, which were dependent on the level of expression of β₂-adrenoceptors.     

Proof of concept pilot study: prevalence of grass virus infection and the potential for effects on the allergenic potency of pollen

Background

Wild plants harbour a variety of viruses and these have the potential to alter the composition of pollen. The potential consequences of virus infection of grasses on pollen-induced allergic disease are not known.

Methods

We have collected pollen from Dactylis glomerata (cocksfoot; a grass species implicated as a trigger of allergic rhino-conjunctivitis) from Wytham Wood, Oxfordshire UK. Extracts were prepared from pollen from uninfected grass, and from grass naturally infected by the Cocksfoot streak potyvirus (CSV). Preparations of pollen from virus-infected and non-infected grasses were employed in skin testing 15 grass pollen-allergic subjects with hayfever. Allergen profiles of extracts were investigated by Western blotting for IgE with sera from allergic subjects.

Results

The prevalence of CSV infection in cocksfoot grasses sampled from the study site varied significantly over an eight-year period, but infection rates of up to 70% were detected. Virus infection was associated with small alterations in the quantities of pollen proteins detected by polyacrylamide gel electrophoresis, and in the patterns of allergens identified by Western blotting with IgE from grass pollen allergic subjects. For individual subjects there were differences in potencies of standardised extracts of pollen from virus-free and virus-infected plants as assessed by skin testing, though a consistent pattern was not established for the group of 15 subjects.

Conclusion

Infection rates for CSV in cocksfoot grass can be high, though variable. Virus-induced alterations in components of grass pollen have the potential to alter the allergenic potency.

     

The Dynamic Assessment and Referral System for Substance Abuse (DARSSA): development, functionality, and end-user satisfaction

The Dynamic Assessment and Referral System for Substance Abuse (DARSSA) conducts a computerized substance abuse assessment; prints personalized summary reports that include tailored substance abuse treatment referral lists; and, for individuals who provide authorization, automatically faxes their contact information to a "best match" substance abuse treatment provider (dynamic referral). After piloting the program and resolving problems that were noted, we enrolled a sample of 85 medical patients. The DARSSA identified 48 (56%) participants who were risky substance users, many of whom had not been identified during their routine medical assessment. Mean satisfaction scores for all domains ranged between "Good" to "Excellent" across patients, nurses, doctors, and substance abuse treatment providers. The median completion time was 13min. Of the 48 risky substance using participants, 20 (42%) chose to receive a dynamic referral. The DARSSA provides a user-friendly, desirable service for patients and providers. It has the potential to improve identification of substance abuse in medical settings and to provide referrals that would not routinely be provided. Future studies are planned to establish its efficacy at promoting treatment initiation and abstinence.     

Struggling behavior during restraint is regulated by stress experience

Restraint elicits a number of physiological stress responses that can be increased or decreased in magnitude based on prior stress history. For instance, repeated exposure to restraint leads to habituation of hypothalamic-pituitary-adrenal (HPA) activation to restraint. In contrast, acute restraint after a different repeated stressor leads to facilitation of HPA activity to the novel stress. Acute restraint also elicits a variety of behaviors, including struggling, but the effect of prior stress in regulating behavioral responses to restraint is not clear. The goal of the present studies was to assess struggling during restraint with or without a prior history of repeated stress. Using automated behavioral analysis software (EthoVision), we quantified struggling during restraint. We found that acutely restrained rats exhibited vigorous struggling behavior that declined during a single restraint period. Repeated restraint lead to habituated struggling behavior, whereas acute restraint after repeated swim elicited facilitated struggling behavior. These effects on struggling were found alongside expected differences in HPA activity. Removing stress-induced increases in corticosterone via adrenalectomy did not significantly affect struggling responses to restraint. Overall, restraint-induced struggling appears to be regulated in a manner similar to HPA responses to restraint, but is not dictated by adrenal hormones.