The impact of a pharmacist-managed dosage form conversion service on ciprofloxacin usage at a major Canadian teaching hospital: a pre- and post-intervention study

Background  

Despite cost containment efforts, parenteral (IV) ciprofloxacin appears to be overutilized at Vancouver General Hospital. In November 2003, the Pharmacist-managed intravenous to oral (IV-PO) Dosage Form Conversion Service was implemented, enabling autonomous pharmacist-initiated dosage form conversion for ciprofloxacin. This study evaluates characteristics of ciprofloxacin use prior to and following implementation of this conversion service.     

Disease control in primary health care: a historical perspective

The effectiveness of disease control by mobile teams decreased when countries became independent. Early case-finding and continuity of care require permanently accessible health care facilities where rationalization by professionals and participation of the users are well balanced. The Primary Health Care concept, a plea for this equilibrium, has been discredited by different types of misapplication. Correctly functioning and accessible first line health services, completed by a referral level, are a precondition for effective participation of the users. Where 'ideal health districts' cannot be realized, a form of steady exchanges between generalists and the specialists of the referral level has lead to diverse 'functional districts'.     

Bordetella holmesii meningitis in a 12-year-old anorectic girl

We describe a 12-year-old anorectic girl with Bordetella holmesii meningitis, the techniques used for its identification, and minimum inhibitory concentrations of antibiotics for 7 B. Holmesii strains collected in the Netherlands during the past 12 years. B. holmesii meningitis has not been previously reported.     

Interferon-gamma gene (T874A and G2109A) polymorphisms are associated with microscopy-positive tuberculosis

Genetic susceptibility to tuberculosis includes several unknown yet different loci each contributing to a small extent. Intronic polymorphisms within the interferon-gamma (IFN-gamma) gene IFNG T+874A and IFNG G+2109A correlate with the IFN-gamma production in vitro, and the frequency of potential high IFN-gamma producers was previously reported by others to be lower in patients than in controls from Sicily. The aim of this study was to determine whether there is an association between polymorphisms in the IFN-gamma gene and predisposition to tuberculosis. We analysed two IFNG SNPs (T+874A and G+2109A) in patients (n = 253) hospitalized in Rijeka (Croatia) and controls (n = 519) from the same area. One-fifth of the controls were healthy contacts of the diseased, and the rest were blood donors. IFNG alleles, their predicted haplotypes or genotypes were not associated with disease susceptibility. Thus, we could not reproduce results from Sicilian case-control study. However, T/T+874 (possible high IFN-gamma producer) and +874A/A (putative low producer) genotypes were associated with microscopically positive-negative forms of disease. Haplotypes (T+874A and G+2109A) based on a prediction by software phase and subsequent genotype analysis corroborated these findings. Patients had significantly higher frequency of genotypes without T at +874 (AA/AA; AA/AG and AG/AG) in microscopy- or bacterial culture-positive groups compared with their negative counterparts. These data suggest an association with disease severity rather than susceptibility to tuberculosis in Croatian Caucasian population.     

Single Nucleotide Polymorphism in the Interleukin 12B Gene is Associated with Risk for Breast Cancer Development

Yellow nail syndrome (YNS) is a rare disorder of unknown aetiology that is characterized by yellow nails associated with lymphoedema and chronic respiratory manifestations. There are no detailed immunological studies in YNS. In this study, we present first extensive immunological analysis of both adaptive and innate immunity in two patients with YNS. One patient has common variable immunodeficiency, whereas second patient has specific antibody deficiency syndrome. Severe lymphopaenia, a striking deficiency of naïve CD4⁺ and CD8⁺ T cells and total B cells, and increased transitional B cells were observed. T cell proliferative response to mitogens and antigens was significantly reduced in both patients. Both patients failed to make specific antibody response to pneumococci. Complement, natural killer cell activity and neutrophil oxidative burst were normal. Immunoglobulin administration resulted in decreased frequency and severity of infections, and an impressive effect was observed on lymphoedema and on the recurrence of pleural effusion. Our data show that YNS is associated with both T and B cell defects. Furthermore, Immunoglobulin may be beneficial in clinical manifestations of lymphoedema.     

High molecular weight kininogen: localization in the unstimulated and activated platelet and activation by a platelet calpain(s)

High mol wt kininogen (HMWK), the major cofactor-substrate of the contact phase of coagulation, is contained within and secreted by platelets. Studies have been performed to localize platelet HMWK in both the unstimulated and activated platelet and to ascertain the effect of platelet enzymes on HMWK itself. On platelet subcellular fractionation, platelet HMWK was localized to alpha-granules, and platelets from a patient with a deficiency of these granules (gray platelet syndrome) had 28% normal platelet HMWK. Platelet HMWK, in addition to being secreted from the platelet, was also localized to the surface of the platelet when activated. Using a competitive enzyme- linked immunosorbent assay for HMWK as an indirect antibody consumption assay, the external membrane of thrombin-activated platelets as well as the releasate from these stimulated platelets had 17 ng HMWK antigen/10(8) platelets available, whereas unstimulated platelets and their supernatant had only 4.9 and 4.2 ng HMWK/10(8) platelets present, respectively. The anti-HMWK antibody consumption by activated normal platelets was specific for membrane-expressed platelet HMWK, since activated platelets from a patient with total kininogen deficiency did not adsorb the anti-HMWK antibody. Enzymes in the cytosolic fraction of platelets cleaved 125I-HMWK (mol wt 120,000) into a mol wt 100,000 polypeptide as well as smaller products at mol wt 74,000, mol wt 62,000, mol wt 47,000, and a few components below mol wt 45,000. No cleavage products were observed when DFP and leupeptin were present. The cleavage of HMWK was specifically prevented by inhibitors of calcium-activated cysteine proteases (leupeptin, N-ethylmaleimide, iodoacetamide, and EDTA) but not by inhibitors of serine proteases (DFP, benzamidine, soybean trypsin inhibitor, or aprotinin). Platelet cytosol increased the coagulant activity of exogenous purified HMWK with maximum HMWK coagulant activity (35-fold) occurring within ten minutes of exposure to platelet cytosol. Treatment of platelet cytosol with leupeptin prevented the increase in the coagulant activity of exogenous HMWK. These studies indicate that activated platelets express platelet HMWK on their external membrane and platelet enzymes can cleave and increase the coagulant activity of exogenous HMWK.