Climatic variables are associated with seasonal acute asthma admissions to accident and emergency room facilities in Trinidad, West Indies

OBJECTIVES: To determine if there is seasonal variation in acute asthmatic visits to accident and emergency (A&E) facilities in Trinidad and to identify the climatic variables associated with such visits. DESIGN AND METHODS: A retrospective census of patients with asthma, defined as those who required emergency bronchodilator nebulization, was taken at two A&E facilities in Trinidad from 1 January 1997 to 31 December 1999. The study included patients aged 64 years and under. Patient demographic data were obtained from the A&E records. Climate variables were taken from the island's sole Meteorological Office. Multiple regression was used to identify climate variables that were independent predictors of A&E asthma visits. RESULTS: There were a total of 45 842 asthma admissions to the two facilities during the study period. Visits exhibited a cyclic pattern over the 3 years that varied according to the island's dry (January-May) and wet (June-December) seasons. There were more visits during the wet season than the dry (40 [SD=2] vs. 32 [SD=2] visits/day; P<0.001). The results of multiple regression indicated that season (P<0.001), barometric pressure (P<0.001), temperature difference (P<0.001), minimum temperature2 (P<0.001) and wind speed2 (P=0.032) were predictors of paediatric visits. Independent predictors of adult visits were season (P<0.001), relative humidity (P<0.001), minimum temperature (P=0.01), temperature difference2 (P<0.001) and minimum temperature2 (P=0.004). Season and climatic variables explained 18% of the variance of the total A&E asthma admissions. CONCLUSION: There is seasonal variation in acute asthma visits to A&E facilities in Trinidad, which remains significant after controlling for climate variables. However, while climate has a role, there are other factors that may also be responsible for increased visits during the wet season. More research is needed to identify these factors.     

Catalytic properties of cholinesterases: importance of tyrosine 109 in Drosophila protein.

Tyrosine 109 in the acetylcholinesterase sequence of Drosophila melanogaster corresponds to an aspartate in vertebrate cholinesterases. Mutation of this amino acid to a glycine in the human butyrylcholinesterase gives rise to the 'atypic' phenotype characterized by a reduced activity for charged compounds. We investigated the importance of tyrosine 109 in the Drosophila sequence by in vitro mutagenesis and its expression in the Xenopus oocyte. We show here that tyrosine 109 contributes to the conformation of the active site and the charge of the residue at position 109 is important for catalytic properties. Sensitivity of the enzyme to organophosphorus and carbamate compounds is modified depending on residues present in position 109, therefore this amino acid is a potential site of resistance for insects to insecticides.     

Gamma-carboxylated isoforms of recombinant human protein S with different biologic properties

Human protein S (HPS), a regulator of hemostasis, is a vitamin K- dependent plasma protein with potential clinical utility. We have obtained high-level expression of the cDNA for HPS in two mammalian cell lines. Both cell lines secreted single chain recombinant HPS (rHPS) in serum-free medium as determined by Western blot analysis. The ability of the rHPS from both cell lines to act as a cofactor for human protein C (HPC) was determined; the rHPS secreted from the human 293 cell line had an activity six times that of the rHPS from the AV12-664 Syrian hamster cell line. Furthermore, the relative specific cofactor activity of rHPS from the 293 cell line was actually 2.5-fold higher than that of single-chain human plasma-derived HPS. Essentially all of the rHPS secreted from the 293 cell line exhibited a calcium-dependent elution profile on anion exchange chromatography, whereas only 25% to 35% of the hamster cell-derived rHPS exhibited this profile. However, the calcium-eluted rHPS from the AV12 cell line had a high specific cofactor activity, equivalent to that of the 293-derived rHPS. A NaCl- elutable rHPS fraction (calcium nondependent) was isolated from the recombinant AV12-664 cell line, further purified, and found to have reduced activity, only 40% that of the calcium-dependent rHPS. The only observable difference in the calcium-dependent and nondependent rHPS molecules was in the content of gamma-carboxyglutamic acid (Gla); the calcium-dependent material contained approximately 10 mol Gla/mol protein whereas the calcium-nondependent material contained only approximately 8 mol Gla/mol of protein. In addition, the calcium- nondependent rHPS had reduced ability to interact with phospholipid vesicles as evidenced by an eightfold increase in the apparent kd. Our data demonstrate the isolation of rHPS with high specific activity, and show that a reduction in as few as two Gla residues dramatically decreases its functional cofactor activity for HPC, due to a reduction in ability to interact with the phospholipid bilayer.     

A novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: the ferric carboxymaltose (FERINJECT) randomized controlled trial

BACKGROUND AIMS:  Anemia is a common complication of inflammatory bowel diseases (IBD) This multicenter study tested the noninferiority and safety of a new intravenous iron preparation, ferric carboxymaltose (FeCarb), in comparison with oral ferrous sulfate (FeSulf) in reducing iron deficiency anemia (IDA) in IBD.
METHODS:  Two hundred patients were randomized in a 2:1 ratio (137 FeCarb:63 FeSulf) to receive FeCarb (maximum 1,000 mg iron per infusion) at 1-wk intervals until the patients' calculated total iron deficit was reached or FeSulf (100 mg b.i.d.) for 12 wk. The primary end point was change in hemoglobin (Hb) from baseline to week 12.
RESULTS:  The median Hb improved from 8.7 to 12.3 g/dL in the FeCarb group and from 9.1 to 12.1 g/dL in the FeSulf group, demonstrating noninferiority ( P = 0.6967). Response (defined as Hb increase of >2.0 g/dL) was higher for FeCarb at week 2 ( P = 0.0051) and week 4 ( P = 0.0346). Median ferritin increased from 5.0 to 323.5 μg/L at week 2, followed by a continuous decrease in the FeCarb group (43.5 μg/L at week 12). In the FeSulf group, a moderate increase from 6.5 to 28.5 μg/L at week 12 was observed. Treatment-related adverse events (AEs) occurred in 28.5% of the FeCarb and 22.2% of the FeSulf groups, with discontinuation of study medication due to AEs in 1.5% and 7.9%, respectively.
CONCLUSIONS:  FeCarb is effective and safe in IBD-associated anemia. It is noninferior to FeSulf in terms of Hb change over 12 wk, and provides a fast Hb increase and a sufficient refill of iron stores.