Accidental over-anticoagulation: substitution error by a foreign pharmacy.

OBJECTIVE: To describe an episode of inadvertent and excessive anticoagulation caused by mistaken substitution of medication by a pharmacy outside the US. CASE SUMMARY: A 57-year-old white woman was found to have profound prolongation of her prothrombin time (56.9 sec) and international normalized ratio (22.18), with other coagulation parameters relatively normal. She had no prior history of bleeding diatheses and was not taking any prescribed anticoagulants. Her coagulopathy rapidly corrected with the administration of fresh frozen plasma and vitamin K. After her medications were visually inspected, it was discovered that she had purchased her prescription medications from a pharmacy in Mexico and that she inadvertently had been taking a preparation of warfarin (proprietary name in Mexico, "Romesa") instead of the prescribed ramipril for her hypertension (proprietary name in Mexico, "Ramace"). After removal of the incorrect medication, she experienced no further prolongation of her coagulation parameters. DISCUSSION: Medication errors contribute significantly to adverse events for patients. The frequency of different types of medication errors is reviewed, and problems specific to the use of warfarin are detailed. Circumstances that might lead to a patient seeking prescription medication outside of the US are also discussed. CONCLUSIONS: The acquisition of prescription medications from pharmacies outside of the US can have adverse consequences, especially if the foreign name of the medication is different from its American name, while sounding similar to other medications that also might be dispensed in foreign pharmacies.

Molecular cloning and characterization of a midgut chymotrypsin-like enzyme from the lesser grain borer, Rhyzopertha dominica.

A cDNA encoding a chymotrypsinogen-like protein in midguts of the lesser grain borer, Rhyzopertha dominica (F.) (Coleoptera: Bostrichidae) was cloned and sequenced. The 901 bp cDNA contains an 816-nucleotide open reading frame encoding 272-amino acids. The predicted molecular mass and pI of the mature enzyme are 23.7 kDa and 4.64, respectively. The encoded protein includes amino acid sequence motifs that are conserved with 5 homologous chymotrypsinogen proteins from other insects. Features of the putative chymotrypsin-like protein from R. dominica include the serine proteinase active site (His(90), Asp(133), Ser(226)), conserved cysteine residues for disulfide bridges, the residues (Gly(220), Gly(243), Asp(252)) that determine chymotrypsin specificity, and both zymogen activation and signal peptides. A TPCK-sensitive caseinolytic protein (P6) with an estimated molecular mass of 24 kDa is present in midgut extracts of R. dominica and can be resolved by electrophoresis on 4-16% polyacrylamide gels. The molecular mass of this caseinolytic enzyme is similar to that of the chymotrypsin deduced from cDNA. Midgut extracts of R. dominica readily hydrolyzed azocasein and N-succinyl-alanine-alanine-proline-phenylalanine-p- nitroanilide (SAAPFpNA), a chymotrypsin-specific substrate. Properties of the enzymes responsible for these activities were partially characterized with respect to distribution in the gut, optimum pH, and sensitivity toward selected proteinase inhibitors. Optimal activity against both azocasein and SAAPFpNA occurs in a broad pH range from about 7 to 10. Both azocasein and SAAPFpNA activities, located primarily in the anterior midgut region, are inhibited by aprotinin, phenylmethyl sulphonylfluoride (PMSF), and soybean trypsin inhibitor (STI). TPCK (N-alpha-tosyl-L-phenylalanine chloromethyl ketone) and chymostatin inhibited more than 60% of SAAPFpNA but only about 10-20% of azocasein activity. These results provide additional evidence for the presence of serine proteinases, including chymotrypsin, in midguts of R. dominica. Arch. Insect Biochem. Physiol. 43:173-184, 2000.Published 2000 Wiley-Liss, Inc.

Characterization of midgut trypsin-like enzymes and three trypsinogen cDNAs from the lesser grain borer, Rhyzopertha dominica (Coleoptera: Bostrichidae).

Protein digestion in the lesser grain borer, Rhyzopertha dominica (F.) (Coleoptera: Bostrichidae), results from the action of a complex of serine proteinases present in the midgut. In this study we partially characterized trypsin-like enzyme activity against N-alpha-benzoyl-L-arginine p-nitroanilide (BApNA) in midgut preparations and cloned and sequenced three cDNAs for trypsinogen-like proteins. BApNAase activity in R. dominica midgut was significantly reduced by serine proteinase inhibitors and specific inhibitors of trypsin, whereas BApNAase activity was not sensitive to specific inhibitors of chymotrypsin or aspartic proteinases. However, trans-epoxysuccinyl-L-leucylamido-(4-guanidino) butane (E-64) inhibited BApNAase activity by about 30%. BApNAase was most active in a broad pH range from about pH 7 to 9.5. The gut of R. dominica is a tubular tract approximately 2.5 mm in length. BApNAase activity was primarily located in the midgut region with about 1.5-fold more BApNAase activity in the anterior region compared to that in the posterior region. Proteinases with apparent molecular masses of 23-24 kDa that were visualized on casein zymograms following electrophoresis were inhibited by TLCK. Three cDNAs for trypsinogen-like proteins were cloned and sequenced from mRNA of R. dominica midgut. The full cDNA sequences consisted of open reading frames encoding 249, 293, and 255 amino acid residues for RdoT1, RdoT2, and RdoT3, respectively. cDNAs RdoT1, RdoT2, and RdoT3 shared 77-81% sequence identity. The three encoded trypsinogens shared 54-62% identity in their amino acid sequences and had 16-18 residues of signal peptides and 12-15 residues of activation peptides. The three predicted mature trypsin-like enzymes had molecular masses of 23.1, 28, and 23.8 kDa for RdoT1, RdoT2, and RdoT3, respectively. Typical features of these trypsin-like enzymes included the conserved N-terminal residues IVGG62-65, the catalytic amino acid triad of serine proteinase active sites (His109, Asp156, Ser257), three pairs of conserved cysteine residues for disulfide bridges, and the three residues (Asp251, Gly274, Gly284) that determine specificity in trypsin-like enzymes. In addition, RdoT2 has both a PEST-like sequence at the C-terminus and a free Cys158 near the active site, suggesting instability of this enzyme and/or sensitivity to thiol reagents. The sequences have been deposited in GenBank database (accession numbers AF130840 for RdoT1, AF130841 for RdoT2, and AF130842 for RdoT3).

NMR spectral assignment of lactone pheromone components emitted by Caribbean and Mexican fruit flies.

By utilizing one- and two-dimensional nuclear magnetic resonance techniques, the complete assignments of the proton and carbon spectra of the lactones anastrephin, epianastrephin, and suspensolide have been accomplished. These compounds are pheromone components for both the Caribbean and Mexican fruit flies. The relative stereochemistries of anastrephin and epianastrephin were demonstrated by nuclear Overhauser difference spectroscopy. With complete spectral assignments now available, biosynthesis of these molecules may be studied by feeding specific isotopically labeled nutrients to flies and subsequently analyzing the volatiles produced for the presence and position of the labelling isotope.

Antibody response to Bordetella pertussis antigens after immunization with American and Canadian whole-cell vaccines.

Because of apparent differences in the incidence and epidemiology of pertussis in the United States and Canada, we measured the antibody response to four Bordetella pertussis antigens and to a whole-bacteria preparation in children immunized with American and Canadian whole-cell pertussis vaccines. All infants received combined pertussis, tetanus, and diphtheria vaccines from one of two American manufacturers or a single Canadian manufacturer. The Canadian children received either oral poliomyelitis vaccine, inactivated poliomyelitis vaccine as a separate injection, or a product that combined inactivated poliomyelitis vaccine with diphtheria, tetanus, and pertussis components. The Canadian trivalent diphtheria, tetanus, and pertussis vaccine given with oral poliovirus vaccine induced lower anti-pertussis toxin antibody titers than did the American vaccines (p < or = to 0.05) but higher antifimbriae and anti-69-kilodalton outer-membrane protein (pertactin) antibody titers (p < or = to 0.02). Canadian children immunized with inactivated poliomyelitis vaccine either as a separate injection or as a combined diphtheria, tetanus, and pertussis vaccine had consistently lower pertussis antibody titers than did those who received oral poliomyelitis vaccine (p < or = 0.001). We conclude that there is a wide range of antibody responses to B. pertussis antigens after immunization with various whole-cell pertussis vaccines, and that these responses may be influenced by concurrent administration of other vaccines.

[Site of BCG vaccine administration and development of hypertrophic scars]. / Sitio de aplicación de la vacuna BCG y desarrollo de cicatrices hipertróficas

In this preliminary report, two groups of children were vaccinated with subcutaneous BCG, one on the deltoid area and the other one on the area between the spine and the scapula. The number of hypertrophic scars on the deltoid area was significantly higher that in the area between the spine and the scapula. Vaccination on this area is as effective in turning the P.P.D. positive as on the deltoid area and the risk of hypertrophic scars in minimized.

Greater frequency of viral respiratory infections in asthmatic children as compared with their nonasthmatic siblings.

A longitudinal clincal and microbiologic surveillance was conducted from October to May, 1971-72, on 16 children with infectious asthma and 15 of their nonasthmatic siblings. Asthmatic children experienced a significantly greater frequency of viral respiratory infections than did nonasthmatic ones (5.1 vs. 3.8 per subject). This increased incidence appeared to be largely the result of a greater number of rhinovirus infections. While respiratory infections of identical etiology that occurred concurrently in an asthmatic and his sibling were equivalent in severity, illnesses were longer (but not significantly so) in asthmatic children.