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Biomedical subjects

M Coyne

Publications and source records attributed to M Coyne.

9 recordsLinked to original sources

Antibiotic use is associated with resistance of environmental organisms in a teaching hospital.

An intensive care unit (ICU), acute stroke unit (ASU) and medical day bed unit (MDBU) underwent a standardized four-month environmental screening programme. The aim was to examine environmental organisms from these wards and compare bacterial resistances in association with antimicrobial usage. Hand-touch and other sites were screened using commercial dip-slides, and staff were asked to provide fingertip cultures. Patient blood isolates were retained throughout the study. Organisms were quantitatively and qualitatively assessed including antimicrobial susceptibility testing. Antibiotic consumption data in defined daily doses/1000 patient-days were obtained for each unit for the previous year. Two hundred and seventy-six staphylococci and 67 Gram-negative bacilli were recovered. Antibiotic resistance was significantly associated with individual wards for staphylococci (P<0.0001) and coliforms (P=0.04), and trends were also demonstrated for other Gram-negative organisms (P=0.06) despite fewer numbers. Antibiotic consumption on the ICU was six-fold higher than on the ASU and MDBU. Associations were found between consumption of selected antibiotic groups and corresponding resistances among staphylococci and Gram-negative bacilli. Antibacterial resistance was the only significant difference between environmental bacteria from different wards, and appeared to reflect prescribing pressure. Visual inspection of a ward may not provide a reliable guide regarding the presence of multi-resistant organisms in the hospital environment or the potential risk of infection. These findings have implications for local antibiotic policies, infection control and cleaning schedules.

Anti-Bacterial Agents↗

Two animal models of retinal degeneration are rescued by recombinant adeno-associated virus-mediated production of FGF-5 and FGF-18.

The goal of these experiments was to evaluate the potential of the fibroblast growth factor family members FGF-5 and FGF-18 to rescue photoreceptors from cell death in retinal degenerative disease. Two strains of transgenic rats, expressing either a P23H or an S334ter rhodopsin mutation, were used as model systems. The neurotrophic growth factors were delivered by subretinal injection of adeno-associated virus vectors, driving expression of the genes with a constitutive CMV promoter. Morphological and functional analyses were performed to determine whether FGF-5 or FGF-18 overexpression could ameliorate cell death in the retina. Immunocytochemistry was used to determine the cellular sites of expression of the factors and to test for up-regulation of FGF receptors due to injection. Significant rescue from photoreceptor cell death was found after injections of vectors expressing either FGF-5 or FGF-18 in the animal models. Increased survival of photoreceptors did not produce a significant increase in electroretinographic responses, however, reflecting either trauma due to the surgery or a suppression of signaling due to expression of proteins. Three weeks after injections, both growth factors were localized to the inner and outer segments of photoreceptors, and the receptors FGFR1 and FGFR2 were also found to be up-regulated in these regions. No visible pathological changes were seen in the FGF-5- or FGF-18-treated eyes. These results indicate that the delivery of either FGF-5 or FGF-18 with adeno-associated virus protects photoreceptors from apoptosis in transgenic rat models of retinitis pigmentosa and that the rescue is probably mediated by conventional receptor tyrosine kinase pathways in photoreceptors.

Animals↗

Recombinant AAV-mediated delivery of a tet-inducible reporter gene to the rat retina.

Viral delivery of neurotrophins or other therapeutic genes is an attractive option for treating retinal degeneration. Regulated expression of these genes in the retina is needed to aid in dose delivery and to promote safety. To evaluate whether tetracycline (tet)-inducible transgenes encapsidated in recombinant adeno-associated viruses (rAAV) can provide controlled gene expression in vitro and in the rat retina, two viruses were constructed: a silencer/activator vector and an inducible doxycycline (dox)-responsive GFP vector. Combinations of these two viruses were subretinally injected into wild-type rats and dox was orally administered through the drinking water. Retinal GFP expression was monitored in vivo with a noninvasive fluorescence imaging method. Eyes were also examined by histology, Western analysis, and electroretinography. Subretinal injection of rAAV efficiently delivers inducible genes to both photoreceptors and retinal pigment epithelial cells. GFP expression was initially observed 1 week postinduction, and GFP protein was undetectable after removal of dox. In uninduced animals, GFP expression was negligible. The dox dosage was varied in vivo and showed a correlation to the level of GFP expression. Thus, transduction of retinal cells with tet-inducible vectors allows for tight regulation of gene expression.

Animals↗

Evaluation of the clinical efficacy of marbofloxacin (Zeniquin) tablets for the treatment of canine pyoderma: an open clinical trial.

The efficacy and field safety of marbofloxacin (Zeniquin) for the treatment of superficial and deep bacterial pyoderma were evaluated. Seventy-two dogs were treated with 2.75 mg kg-1 of marbofloxacin orally once daily for 21 or 28 days. Sixty-two dogs (86%) had superficial pyoderma and 10 (14%) had deep pyoderma. A history of prior pyoderma was reported in 39/72 dogs. Pretreatment aerobic bacteriologic cultures of skin lesions were performed in 47 cases and the predominant pathogen isolated was Staphylococcus intermedius. Treatment was successful in 62/72 (86.1%) dogs, improvement was noted in 6/72 (8.3%) dogs and treatment failed in 4/72 (5.6%) dogs. Adverse effects associated with treatment included listlessness, anorexia, vomiting, soft stool, flatulence and polydipsia; these adverse effects were seen in only 6/81 dogs. Marbofloxacin was safe and effective for the treatment of superficial and deep pyoderma in dogs at the dosage used in this study.

Administration, Oral↗

Implementation of intraosseous infusion technique by aeromedical transport programs.

Aeromedical transport program implementation of intraosseous infusion (IOI) was ascertained by telephone survey. One hundred thirty-three programs were polled: 69.2% had never utilized IOI nor were considering its use; 13.5% had previously utilized IOI; 15.8% had not yet implemented IOI but had been in-serviced on the technique; and 1.5% were considering implementation. Of 39 programs previously in-serviced or presently utilizing the procedure, seven restricted IOI insertion to physicians while 32 permitted placement by nurses or paramedics. Half of the programs would pursue IOI immediately after a 5-minute trial of peripheral line placement in preference to cutdown or central venous line attempts. About 50 IOI were performed by aeromedical transport personnel in 1986. Rate of successful insertion was approximately 80%. Complications were few and minor. This survey demonstrates that the simple, safe technique of IOI is being grossly under-utilized and warrants further consideration.

Aircraft↗

Propranolol inhibits adenylate cyclase and secretion stimulated by deoxycholic acid in the rabbit colon.

Bile acids cause diarrhea by inducing colonic secretion, probably mediated through the cyclic AMP system. The aim was to determine the effects of an adenylate cyclase inhibitor, propranolol, on deoxycholic acid (DCA) stimulation of net secretion and the cyclic AMP system in the colon. In each of 30 New Zealand white rabbits, 0.9% NaC1 as control and 6 mM and 8 mM DCA were injected in random sequence into three colonic loops in situ. Propranolol, 4 mg per kg was administered intravenously to 12 of the 30 rabbits 1/2 hr before preparation of the loops, i.e., 5 1/2 hr before the rabbits were killed. In the 18 untreated animals, 6 and 8 mM DCA significantly stimulated colonic net secretion and mucosal adenylate cyclase activity; 6 mM DCA caused no change in mucosal phosphodiesterase activity, whereas 8 mM DCA caused a 25% decrease (P less than 0.01). In propranolol-treated animals compared to untreated animals, the volume of luminal fluid in controls was not different, with 6 mM DCA it was 88% less (P less than 0.01), and with 8 mM DCA it was 45% less (P less than 0.01); adenylate cyclase activity in controls was 43% less (P less than 0.01), with 6 mM DCA it was 67% less (P less than 0.01), and with 8 mM DCA it was 65% less (P less than 0.01); phosphodiesterase activity in controls and with 6 mM DCA was not different and with 8 mM DCA it was 38% greater (P less than 0.02). In conclusion, propranolol prevented DCA stimulation of colonic net secretion and inhibited the cyclic AMP system. Propranolol, therefore, warrants investigation as therapy for diarrhea caused by bile acids in the colon.

Adenylyl Cyclase Inhibitors↗