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Biomedical subjects

J Hamilton-Miller

Publications and source records attributed to J Hamilton-Miller.

8 recordsLinked to original sources
PubMed1998

Cefixime for switch therapy.

Switch therapy, or step-down therapy, is the concept of switching from an intravenous antibiotic to an oral preparation after a few days, once the condition of the patient has improved and the pathogen and its susceptibility have been determined. The orally active third-generation cephalosporin cefixime is a primary candidate for switch therapy owing to its very good efficacy and safety profile. Preliminary studies have shown excellent clinical outcomes with switch therapy to cefixime after 2-3 days for a variety of serious infections. Importantly, dramatic cost benefits have also been found, particularly with respect to reduced length of hospital stays. However, guidelines are required to indicate under what conditions switch therapy is appropriate, and awareness must be developed within hospitals among physicians, pharmacists and administrators alike.

Administration, Oral↗
PubMed1995

Detection of M2 antibodies in patients with recurrent urinary tract infection using an ELISA and purified PBC specific antigens. Evidence for a molecular mimicry mechanism in the pathogenesis of primary biliary cirrhosis?

Primary Biliary Cirrhosis (PBC) is a chronic liver disease of unknown aetiology. The main characteristic feature of the disease is the presence of circulating antimitochondrial antibodies (AMA) to components (collectively named M2) of the mitochondrial 2-oxo-acid multienzyme complexes; pyruvate, oxoglutarate and branched chain oxo-acid dehydrogenase complexes. As these enzymes are phylogenetically conserved, AMA also exhibit reactivity against a range of microorganisms. PBC patients have an increased incidence of recurrent urinary tract infection (UTI) compared to other chronic liver disease controls. Interestingly, we have recently detected low titre AMA in patients with a history of recurrent UTI but normal liver function using crude bovine heart mitochondrial preparations and immunoblotting techniques. Here we confirm these findings using purified M2 antigens and ELISA. We found that 52% of "normal" subjects with a history of recurrent UTI had AMA specifically to M2 antigens. The percentage was significantly higher than that found for chronic liver disease (19%, p < 0.01) and normal controls (4%, p < 0.001). These results support our hypothesis for molecular mimicry in PBC. We propose that a bacterial trigger, possibly resulting from recurrent UTIs, is responsible for initiating an autoimmune response in a predisposed host because of a cross-reactivity between mitochondrial and bacterial antigens.

Antibody Specificity↗
PubMed1989

Antimitochondrial antibodies in primary biliary cirrhosis recognize both specific peptides and shared epitopes of the M2 family of antigens.

Sera from patients with primary biliary cirrhosis exhibit variable autoantibody reactivity against mitochondria, the commonest antigen (designated M2) including three structures of approximate M.W. 70, 50 and 40 kD. The nature of these antigens has only recently been established; the 70 and 50 kD are the transacetylase E2 and component X, respectively, of the pyruvate dehydrogenase complex and are distinct polypeptides. We have demonstrated, by immunoblotting, elution and rebinding of antibodies, unequivocal cross-reactivity between the major bands of the M2 antigen. In addition, cross-reactivity has been shown between antibodies binding to each of the three M2 bands of mitochondria and two major antigenic bands of both Gram-negative and Gram-positive bacteria. Conversely, antibodies eluted from these two bands of Escherichia coli were found to bind all three M2 bands of mitochondria. These results suggest that the antibodies of primary biliary cirrhosis contain both peptide-specific and cross-reacting antibodies, the latter recognizing a common "M2 epitope" that might include nonprotein components of the peptides. However, direct and competitive enzyme-linked immunosorbent assays failed to implicate the coenzyme of the pyruvate dehydrogenase complex, lipoic acid or its amide, as the common antigenic moiety.

Autoantibodies↗
PubMed1989

Ciprofloxacin resistance in methicillin- and gentamicin-resistant Staphylococcus aureus.

A total of 112 Staphylococcus aureus strains resistant to methicillin and gentamicin were collected from 31 centres in 22 countries worldwide. Many strains were multi-resistant. In tests to determine the susceptibility of the organisms to ciprofloxacin 16 strains (14.3%), originating from France, the FRG, Israel and Italy, were shown to be resistant to this agent. To limit ciprofloxacin resistance, a reappraisal is necessary of fluoroquinolone usage against methicillin- and gentamicin-resistant Staphylococcus aureus.

Ciprofloxacin↗
PubMed1979

Comparison of pivmecillinam and cephradine in bacteriuria in pregnancy and in acute urinary tract infection.

48 non-pregnant domiciliary patients referred by general practitioners and 50 pregnant women were treated for bacteriuria with either 500 mg cephradine or 400 mg pivmecillinam every 6 h for 7 days. In the pregnant women, cure rates were over 90% after 2 weeks for both compounds, and after 6 weeks were 86% for cephradine and 78% for pivmecillinam. Cure rates in the non-pregnant were 83% for cephradine and 95% for pivmecillinam at 6 weeks. Seven patients (3 given cephradine, 4 given pivmecillinam) stopped treatment due to side-effects. Overall, side-effects (many of which were trivial) were more common in patients treated with cephradine (51%) than in those receiving pivmecillinam (33%). It is concluded that both drugs are highly effective in these two common types of urinary infection.

Adult↗