Repeat skin testing for aeroallergen immediate hypersensitivity in an atopic patient population

A retrospective study of repeat intradermal skin testing with aeroallergens carried out on atopic subjects with allergic rhinitis/conjunctivitis and/or asthma, after a mean interval of 3.5 years, showed that an increase in the number of allergens reacted to by an individual patient correlated with age or with worsening of symptoms.     

The earliest cognitive change in a person with familial Alzheimer''s disease: presymptomatic neuropsychological features in a pedigree with familial Alzheimer''s disease confirmed at necropsy.

Comprehensive, longitudinal neuropsychological assessments are reported in a person "at risk" from autosomal dominant, necropsy confirmed familial Alzheimer's disease. The first assessment showed a moderately selective verbal memory deficit in the context of mild general intellectual impairment. Subsequent testing showed the progressive deterioration of visual memory and a mild decline of perceptual and spatial skills. Language and literacy skills, however, remained comparatively intact. The neuropsychological profiles obtained at each assessment are presented in profile maps. These permit direct longitudinal comparison of cognitive function, and may serve in the comparison of different potential cases of familial Alzheimer's disease. This case sought medical attention for memory difficulties 26 months after the first neuropsychological assessment. These results mark the first cognitive manifestations in a pedigree with familial Alzheimer's disease which, in this case, were seen presymptomatically. The findings are discussed in relation to neuropsychological studies of affected cases, and in terms of their reflecting the heterogeneous nature of familial Alzheimer's disease.     

Clinical pharmacology of moclobemide, a new reversible monoamine oxidase inhibitor

The clinical pharmacology of the new reversible monoamine oxidase (MAO) inhibitor, moclobemide, was examined in three separate studies in healthy male volunteers. In a single oral dose study, moclobemide (25-150 mg) was rapidly absorbed from the gastrointestinal tract and had a relatively short plasma half-life (mean 1.3 h after 150 mg). A decrease in the plasma concentrations of the noradrenaline metabolite 4- hydroxy-3-methoxyphenylglycol (HMPG), however, indicated a longer time to peak pharmacodynamic effect and longer duration of activity. Assay of platelet MAO activity did not reveal any evidence of irreversible inhibition of the B form of the isoenzyme. Single oral doses of moclobemide (150 and 300 mg) significantly lowered the threshold to the cardiovascular effects ('cheese reaction') of intravenous tyramine. However, after repeated administration of 100 mg three times daily for over 2 weeks, moclobemide caused significantly less potentiation than did phenelzine (15 mg three times per day) on the cardiovascular effects of oral tyramine, a clinically more relevant model. The MAO-B inhibitor, selegiline (5 mg once daily), also lowered the oral tyramine threshold significantly. Moclobemide was generally well tolerated by these healthy volunteers.     

Diagnosis of pulmonary embolism: Ventilation perfusion scintigraphy versus helical computed tomography pulmonary angiography

The present study compared the accuracy of ventilation perfusion scintigraphy (VQS) and CT pulmonary angiography (CTPA) for the diagnosis of pulmonary embolism. This was a prospective observational study of 112 patients with suspected pulmonary embolism (PE) who could be studied with both investigations within 24 h. Results were compared to final diagnosis at completion of 6-month follow up, using receiver operating characteristic (ROC) analysis. Pulmonary embolism was diagnosed in 27 referred patients (24%). The sensitivity and specificity of VQS and CTPA were similar to that reported from the literature. A normal VQ scan had the highest negative predictive value (100%), while a high-probability VQ scan had the highest positive predictive value (92%). There was no overall difference (area under the ROC curve (AUC)) between VQS (AUC (95% CI) = 0.82 (0.75,0.89)) and CTPA (AUC = 0.88 (0.81,0.94)) for the diagnosis of PE. Among patients with abnormal chest X-rays, CTPA (AUC 0.90 (0.83,0.97)) appeared somewhat better than VQS (AUC 0.78 (0.68,0.88)) but this difference did not reach statistical significance. In this instance, CTPA is at least as accurate as VQS and may provide an opportunity to make alternative diagnoses.     

A Multipreceptor Approach to Ambulatory Care Topic Discussions

Objective. To assess the impact of a multipreceptor approach to facilitating topic discussions on students'' knowledge and confidence in clinical decision-making during an ambulatory care advanced pharmacy practice experiences (APPEs).Design. Faculty members with relevant expertise and experience facilitated discussions with fourth-year doctor of pharmacy (PharmD) students regarding 7 ambulatory care topics. A student self-assessment survey and knowledge-assessment instrument was administered before and after discussions.Assessment. Students'' examination scores increased significantly from 59.1% ± 13.9% at baseline to 76.5% ± 12.6% at the end of the 5-week experience (p<0.001). The majority of participants were comfortable making therapeutic decisions regarding medication use as it related to all discussion topics except heart failure.Conclusions. Participation in topic discussions led by faculty members with expertise and experience for each ambulatory care topic was associated with a significant improvement in knowledge-assessment scores.     

Assessment of Hageman factor activation in human plasma: quantification of activated Hageman factor-C1 inactivator complexes by an enzyme- linked differential antibody immunosorbent assay

An enzyme-linked immunosorbent assay has been developed for the quantitation of activated Hageman factor-C1 inactivator (HF-C1 INH) complexes. Addition of increasing quantities of either of the major forms of activated Hageman factor (HFa or HFf) to normal plasma or to Hageman factor-deficient plasma leads to a dose-dependent increase in activated HF-C1 INH complexes. As little as 0.5 micrograms/mL of activated HF added to plasma can be detected, corresponding to activation of approximately 2% of plasma HF. The sensitivity of the assay is increased at least tenfold when complexes are formed in HF- deficient plasma, indicating competition between unactivated HF and activated HF-C1 INH complexes for binding to the antibody. Specificity is demonstrated in that addition of activated HF to hereditary angioedema plasma yields less than 1% of the activated HF-C1 INH complex formation obtained with normal plasma. Kaolin activation of HF- deficient plasma yields no detectable complex formation. Kaolin activation of prekallikrein-deficient plasma demonstrates a time- dependent increase in formation of activated HF-C1 INH complex consistent with the ability of HF in this plasma to autoactivate as the time of incubation with the surface is increased. Kaolin treatment of high-molecular weight (HMW) kininogen-deficient plasma yields an even more profound abnormality in the rate of formation of activated HF-C1 INH complexes reflecting the complex role of HMW kininogen in the initiation of contact activation. Although addition of corn inhibitor to plasma prevents activated HF-C1 INH complex formation, it does not inhibit activated HF sufficiently fast to prevent prekallikrein activation.     

Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia.     

The differential dependence of abstract and concrete words upon associative and similarity-based information: Complementary semantic interference and facilitation effects

We report mirror-image effects of interference and facilitation in the semantic processing of identical sets of abstract and concrete words in a patient F.B.I. with global aphasia following a large left middle cerebral artery stroke. Interference was elicited when the tasks involved comprehending the spoken form of each word, but facilitation was found when the patient read aloud the written forms of the same words. More importantly, irrespective of whether the dynamic effect was one of facilitation or interference, effects of semantic association were observed for abstract words, whilst effects primarily of semantic similarity were observed for concrete words. These results offer further neuropsychological evidence that the more abstract a word, the greater its dependence upon associative information and the smaller its dependence upon similarity-based information. The investigations also contribute to a converging body of evidence that suggests that this theory generalizes across different experimental paradigms, stimuli, and participants and also across different cognitive processes within individual patients. The data support a graded rather than binary or ungraded model of the relationships between concreteness, association, and similarity, and the basis for concrete words’ greater dependence upon similarity-based information is discussed in terms of the development of taxonomic structures and categorical thought in young children.