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Biomedical subjects

A Franklin

Publications and source records attributed to A Franklin.

At least 19 recordsLinked to original sources
PubMed1999

Genetic basis of macrolide and lincosamide resistance in Brachyspira (Serpulina) hyodysenteriae.

Macrolide antibiotic resistance is widespread among Brachyspira hyodysenteriae (formerly Serpulina hyodysenteriae) isolates. The genetic basis of macrolide and lincosamide resistance in B. hyodysenteriae was elucidated. Resistance to tylosin, erythromycin and clindamycin in B. hyodysenteriae was associated with an A-->T transversion mutation in the nucleotide position homologous with position 2058 of the Escherichia coli 23S rRNA gene. The nucleotide sequences of the peptidyl transferase region of the 23S rDNA from seven macrolide and lincosamide resistant and seven susceptible strains of Brachyspira spp. were determined. None of the susceptible strains were mutated whereas all the resistant strains had a mutation in position 2058. Susceptible strains became resistant in vitro after subculturing on agar containing 4 micrograms ml-1 of tylosin. Sequencing of these strains revealed an A-->G transition mutation in position 2058.

Anti-Bacterial Agents↗
PubMed1999

Possible interaction of genotypes at cystathionine beta-synthase and methylenetetrahydrofolate reductase (MTHFR) in neural tube defects. NTD Collaborative Group.

Neural tube defects are a common, complex disorder with genetic and environmental components to risk. We investigated the previously reported interaction between homozygosity for the thermolabile variant at the methylenetetrahydrofolate reductase and heterozygosity for the 844ins68 allele at the cystathionine beta-synthase loci in cases with lumbosacral myelomeningocele and their parents. Using control allele frequencies from our sample pooled with those published in the literature, we confirm a marginally significant interaction at these two loci. This finding suggests that additional, larger studies are warranted to investigate this possible interaction in more detail.

Alleles↗
PubMed1999

Repeated administration of trimethoprim/sulfadiazine in the horse--pharmacokinetics, plasma protein binding and influence on the intestinal microflora.

Six healthy adult horses were given repeated administrations of trimethoprim/ sulfadiazine (TMP/SDZ) intravenously (i.v.) (2.5 mg/kg TMP and 12.5 mg/kg SDZ) and orally (p.o.) as a paste (5 mg/kg TMP and 25 mg/kg SDZ). Both formulations were given twice daily for 5 days, with a 3-week interval between i.v. and oral administration. The influence of the drug combination on the intestinal microflora was examined and the plasma concentrations, pharmacokinetic parameters and plasma protein binding were determined. There were no major changes in the bacterial intestinal flora and no clinical evidence of gastrointestinal disturbances following the i.v. and oral TMP/SDZ administration. An initial reduction in the number of coliform bacteria during the treatment was notable, though with no evident difference between i.v. and oral treatment. The minimum concentration during a dose interval at steady state (Cminss), the elimination half-life (t1/2beta) and the mean residence time (MRT) were significantly greater after oral administration compared to i.v. for both TMP and SDZ. The plasma protein binding was measured to be 20% for SDZ and 35% for TMP. Oral administration of TMP/SDZ in a dose of 30 mg/kg given twice daily in the form of paste appeared as a satisfactory method for obtaining plasma levels above MIC (minimum inhibitory concentration in vitro) values during the interdosing interval.

Administration, Oral↗
PubMed1999

Pharmacokinetics of sulphadiazine-trimethoprim in lactating dairy cows.

Five Finnish Ayrshire cows in mid or end-lactation were treated with 40 mg sulphadiazine/kg and 8 mg trimethoprim/kg using intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) routes. Elimination of sulphadiazine was not affected by the route of administration (median t1/2 4.4-5.0 h) while elimination of trimethoprim was strongly limited by slow absorption from the injection site after s.c. and i.m. administration (median for apparent t1/2 21-25 h) compared to that after i.v. administration (median t1/2 1.2 h; p < 0.05). The median bioavailability of trimethoprim was also decreased, being 37% and 55% after s.c. and i.m. administration, respectively. When i.v. administration was used, trimethoprim concentration exceeded 0.1 mg/l in milk between 0.15-8 h while sulphadiazine concentrations above 2 mg/l were maintained from 0.5-2 h to 8 h. After s.c. and i.m. administration sulphadiazine in milk behaved similar to that after i.v. administration, while trimethoprim time-concentration curves were flat and trimethoprim concentrations were around 0.1 mg/l for an extended period of time (8-12 h). Median Cmax values in milk were only 0.07 mg/l and 0.10 mg/l for s.c. and i.m. administrations, respectively. After s.c. administration, 4 out of 5 cows showed signs of pain. After i.m. administration, 2 of the cows showed clear signs of pain and one had some local tenderness at the site of injection.

Animals↗
PubMed1998

Effects of ischemic preconditioning on myocardial perfusion, function, and microvascular regulation.

BACKGROUND: Ischemic preconditioning (PC) has been advocated as a method to preserve myocardial function and perfusion during minimally invasive direct coronary bypass (MIDCAB). We examined the effects of PC on indexes of myocardial function, perfusion, and endothelial and beta-adrenergic coronary regulation after 30 minutes of ischemia and 60 minutes of reperfusion (IR). METHODS AND RESULTS: Five groups of pigs were studied: (1) PC-IR: PC by 3 cycles of 5-minute left anterior descending coronary artery occlusion (CO) and 5-minute reperfusion (Rep) + 30 minutes of CO + 60 minutes of Rep; (2) IR alone: 30 minutes of CO + 60 minutes of Rep; (3) PC alone; (4) PC-IR-glibenclamide (GLIB): PC-IR + infusion of GLIB; (5) control: noninstrumented. Reactivity (in vitro) of coronary arterioles (70 to 150 microns) from the myocardial area at risk was examined with video microscopy. beta-Adrenergic microvascular relaxations to isoproterenol, forskolin, and 8-bromo-cAMP were significantly reduced after IR alone (P < 0.05 versus control, 2-way ANOVA). PC before IR restored these responses to normal (P < 0.05 PC-IR versus IR alone), and GLIB abolished this effect of PC. Subepicardial endothelium-dependent microvascular relaxation to ADP was significantly reduced after IR alone (P < 0.01 versus control) but was preserved in both the PC-IR and PC-IR-GLIB groups (P < 0.05 versus IR alone). The response of vessels to ADP from the subendocardium was significantly reduced in all groups compared with the control response (all P < 0.05 versus control). Nitroprusside elicited a similar response in vessels from all groups. PC before IR did not affect the reduced myocardial percent segmental shortening or left ventricular maximal dP/dt, did not affect myocardial perfusion in the subepicardium or subendocardium, and did not change expression of the inducible or the constitutively expressed isoforms of nitric oxide synthase. CONCLUSIONS: PC before IR preserves beta-adrenergic signal transduction in coronary smooth muscle through a KATP channel mechanism, whereas PC preserves endothelium-dependent relaxation in the subepicardium through a mechanism not related to KATP channels or the enhanced expression of nitric oxide synthase. Nevertheless, PC does not improve short-term myocardial function or baseline myocardial perfusion after IR. Thus, the short-term beneficial role of PC in myocardial protection during MIDCAB may be limited.

Adrenergic beta-Agonists↗
PubMed1998

Myocardial VEGF expression after cardiopulmonary bypass and cardioplegia.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a heparin-binding glycoprotein that plays a critical role in angiogenesis, vascular remodeling, and regulation of vascular tone and permeability. Because myocardial and peripheral edema and systemic hypotension occur frequently after cardiac operations, we examined the effects of cardiopulmonary bypass (CPB) and cardioplegia on gene expressions of VEGF protein and the VEGF tyrosine kinase receptor flk-1 and coronary vascular responses to VEGF. METHODS AND RESULTS: Pigs (n = 6) were placed on normothermic CPB and hearts were arrested for 1 hour with a hyperkalemic, cold blood cardioplegic solution. Pigs were then separated from CPB and perfused off CPB for an additional 2 hours. Myocardial and skeletal muscle specimens were obtained for Northern analysis of VEGF protein, flk-1 receptor, and basic fibroblast growth factor (bFGF) mRNA before CPB and after 2 hours of reperfusion. Isolated, precontracted coronary arterioles in pre-CPB dilated potently to exogenous VEGF (dilation = 26 +/- 4% of precontraction at 10(-12) mol/L VEGF). Cardioplegia-reperfusion was associated with a 4 +/- 2-fold (P < 0.05 vs pre-CPB) increase in myocardial VEGF protein mRNA, whereas no similar increase was observed in the skeletal muscle. Flk-1 mRNA was increased 6 +/- 3-fold (P < 0.05 vs pre-CPB) after reperfusion, whereas it was unchanged in the skeletal muscle. Relaxations of precontracted coronary arterioles to VEGF were significantly increased (40 +/- 6% at 10(-12) mol/L, P < 0.05 vs pre-CPB) after 2 hours of reperfusion, but those to the endothelium-dependent vasodilator ADP and the endothelium-independent vasodilator nitroprusside were not changed, suggesting that the VEGF receptors remain intact and function is selectively upregulated. In contrast, relaxation responses of microvessels to bFGF were not altered after cardioplegia-reperfusion, and there was no increase in bFGF mRNA in either myocardium or skeletal muscle. CONCLUSIONS: This study shows that VEGF protein and its flk-1 receptor gene expressions are selectively increased and the potent VEGF-induced vascular responses are enhanced in the coronary microcirculation after blood cardioplegia. The respective parameters are unchanged in the skeletal muscle after normothermic CPB. These findings may have important implications regarding postoperative coronary blood flow regulation, increases in myocardial edema, and vascular remodeling after cardioplegia-reperfusion.

Animals↗
PubMed1998

Clostridium difficile associated with acute colitis in mares when their foals are treated with erythromycin and rifampicin for Rhodococcus equi pneumonia.

In Sweden, mares sometimes develop acute, often fatal, colitis when their foals are treated orally with erythromycin and rifampicin for Rhodococcus (R.) equi infection. Clostridium (C.) difficile, or its cytotoxin, was demonstrated in faecal samples from 5 of 11 (45%) mares with diarrhoea. By contrast C. difficile was not found in the faecal flora of 12 healthy mares with foals treated for R. equi infection or in 56 healthy mares with healthy untreated foals. No other enteric pathogen was isolated from any diarrhoeic mare. Of 7 investigated treated foals, 4 had a high (1651.0, 1468.3, 273.0 and 88.8 microg/g) faecal concentration of erythromycin. The dams of those 4 foals developed acute colitis, whereas the dams of 3 foals with a lower (26.3, 4.6 and 3.7 microg/g) faecal erythromycin concentration remained healthy, indicating that there might have been an accidental intake of erythromycin by mares. The foals treated with antibiotics were regarded as asymptomatic carriers and potential reservoirs, as C. difficile was found in 7 of 16 foals investigated, while 56 untreated foals proved negative. The isolated C. difficile strains proved resistant to both erythromycin (MIC>256 mg/l) and rifampicin (MIC>32 mg/l), a fact that may have favoured the growth of C. difficile in the foal intestine. All mares found positive for C. difficile were, or had recently been, hospitalised together with their foals, indicating that C. difficile may be a nosocomial infection, in horses. The results emphasise that routine testing for C. difficile and its cytotoxin is recommended when acute colitis occurs in mares when their foals are treated with erythromycin and rifampicin. Preventive measures in order to avoid accidental ingestion of erythromycin by mares from the treatment of their foals are suggested.

Actinomycetales Infections↗
PubMed1998

Doing it all in the public eye: a comparative analysis of California district hospital affiliations.

California contains 74 hospital districts, which are local governmental entities with publicly elected boards. Historically, they have been responsible for operating hospitals in remote areas to provide for the health care needs of their communities. Because the health care market has become increasingly competitive and because some of these once rural areas have grown into large cities, these districts are seeking partners for their hospitals in hopes of preserving their long-term financial viability. The terms reached in these transactions are discussed in the article.

California↗
PubMed1997

[Animal husbandry and food handling today. Current food preservation has changed the intestinal flora].

In the modern world, as refrigerated storage has replaced lactic acid fermentation methods of food preservation, we no longer ingest large quantities of live lactobacilli with our food, but relatively large numbers of potentially pathogenic Gram-negative bacteria instead. In the brave new world, antibiotics are used as growth-promoting additives in animal feed in every country but Sweden. The antibiotics used in Europe at low dosages, and exempt from prescription requirements, include macrolides, streptogramins and nitro-imidazoles. There is reason to believe that avoparcin, recently banned in Europe as an antibiotic animal feed additive, has contributed to the occurrence of vancomycin-resistant enterococci in humans. Animal foodstuffs production in Europe and the USA is so intensive that it provides very favourable conditions for the spread of bacteria. Pig, cattle and poultry breeding in Europe are beset by formidable difficulties in the form of Salmonella infections, which constitute not only a hygiene but also a clinical problem. Sweden, the bravest of brave new worlds, faces an increase in the influx of domestic animals and foodstuffs from other countries, and in general less restrictive regulations concerning food production and animal husbandry, but reduced powers of control. Thus, we may expect problems both with pathogens (traditional ones such as Salmonella, and potential ones such as food-spoilage Gram-negative bacteria), and with antibiotic-resistant bacteria in our food-stuffs, to become greater.

Animal Husbandry↗
PubMed1997

Effects of magnesium cardioplegia on regulation of the porcine coronary circulation.

We compared the effect of hypermagnesium and hyperkalemic crystalloid cardioplegia on beta-adrenoceptor-mediated and endothelium-dependent relaxation and myogenic responses of coronary arterioles. Pigs were placed on cardiopulmonary bypass. Hearts were arrested with cold hypermagnesium (25 mM Mg2+, hyper-Mg, n = 12) or hyperkalemic (25 mM K+, hyper-K, n = 12) crystalloid cardioplegia for 1 hr. Hearts of selected pigs (n = 6 in each group) were then reperfused for 1 hr. In vitro relaxation responses of acetylcholine-pre-contracted arterioles were studied in a pressurized no-flow state with video-microscopy. Relaxation of pre-contracted coronary microvessels (70-150 microns) to isoproterenol (beta-adrenergic agonist) and forskolin (adenylate cyclase activator) was preserved after cardioplegia using a hyper-Mg solution. In contrast, responses were impaired to isoproterenol [P < 0.01 (two-factor ANOVA) vs. controls, n = 6] and forskolin (P < 0.01) after hyper-K cardioplegia. After 1 hr of reperfusion, relaxation responses to isoproterenol and forskolin were partially recovered. Hyper-Mg cardioplegia and post-cardioplegic reperfusion did not affect receptor-mediated endothelium-dependent relaxation to ADP, non-receptor-mediated endothelium-dependent relaxation to A23187, and endothelium-independent relaxation to nitroprusside. However, responses to ADP (P < 0.01) and A23187 (P < 0.05) were selectively impaired after hyper-K cardioplegia. Myogenic contraction was impaired after either hyper-Mg or hyper-K cardioplegia. Left ventricular systolic pressure, coronary blood flow, and +dP/dt were similar after hyper-Mg or hyper-K cardioplegia. These results suggest that hyper-Mg cardioplegia is superior to hyper-K cardioplegia in terms of preserving beta-adrenoceptor-mediated and endothelium-dependent regulation of the coronary microcirculation, yet it has minimal if any additional beneficial effect on preserving myogenic responses or myocardial contractile function.

Adrenergic beta-Agonists↗
PubMed1997

Comparative effects of continuous warm blood and intermittent cold blood cardioplegia on coronary reactivity.

BACKGROUND: Cardioplegia is known to affect coronary vascular reactivity. We examined the effects of intermittent cold and continuous warm blood cardioplegia on beta-adrenoceptor-mediated, adenosine triphosphate-sensitive K+ (K+ATP)-channel-mediated, and endothelium-dependent relaxation and on the myogenic tone of coronary arterioles. METHODS: Pigs were placed on cardiopulmonary bypass. Hearts were arrested for 1 hour with a cold blood cardioplegic solution administered intermittently (n = 12; iCB-CP) or with a warm blood cardioplegic solution delivered continuously (n = 12; cWB-CP). Selected hearts (n = 6 in each group) were then reperfused for 1 hour. In vitro relaxation responses of precontracted microvessels (50 to 160 microns) were studied in a pressurized no-flow state. RESULTS: Relaxation in response to isoproterenol (beta-adrenergic agonist) was similar after iCB-CP and cWB-CP, whereas forskolin (adenylate cyclase activator)-induced relaxation was impaired more after iCB-CP than after cWB-CP. After reperfusion the respective responses were similar. Both iCB-CP and cWB-CP preserved receptor-mediated, endothelium-dependent relaxation in response to adenosine, 5'-diphosphate; non-receptor-mediated endothelium-dependent relaxation in response to A23187; endothelium-independent cyclic guanosine monophosphate-mediated relaxation in response to sodium nitroprusside, and K+ATP-channel-mediated relaxation. Relaxations in response to 8-bromo-cyclic guanosine monophosphate (a cyclic guanosine monophosphate-dependent protein kinase activator) and to 8-bromo-cyclic adenosine monophosphate (a cyclic adenosine monophosphate-dependent protein kinase activator) were impaired after iCB-CP alone and after reperfusion, whereas the respective responses were not affected after cWB-CP. Myogenic tone was decreased similarly after iCB-CP and cWB-CP but was not further altered after reperfusion. Cardiac function was similar after iCB-CP and cWB-CP. CONCLUSIONS: These results suggest that cWB-CP is similar to iCB-CP in its ability to preserve endothelium-dependent relaxation and K+ATP-channel function. The superior preservation of beta-adrenergic-cyclic adenosine monophosphate-mediated coronary responses after cWB-CP is brief and associated with minimal improvement of myocardial function and myogenic tone.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1997

Pharmacokinetics of penicillin-G in ewes and cows in late pregnancy and in early lactation.

Concentrations of penicillin-G in serum were determined after single intravenous doses of potassium penicillin-G (10 mg/kg body wt) to ewes and cows in late pregnancy and in early lactation. Penicillin-G in serum was analysed by a microbiological method and pharmacokinetic parameters were calculated by model-independent methods. Serum concentrations were lower in early lactation than in late pregnancy in both ewes and cows. The differences were statistically significant at most sampling times in ewes but only during the first hour in cows. Weight corrected values of clearance and volume of distribution were significantly higher in early lactation than in late pregnancy in both ewes and cows. Mean residence time and elimination-half life were shorter in lactating than in pregnant ewes, however for the latter parameter the difference was not statistically significant. Neither of these parameters changed in cows. It is concluded that in both ewes and cows pharmacokinetic parameters of penicillin-G are altered from late pregnancy to early lactation but that these changes have little practical impact and do not call for a revised dosage regime of the studied drug.

Animals↗
PubMed1997

Outcome of African American men screened for prostate cancer: the Detroit Education and Early Detection Study.

PURPOSE: Will early detection impact on stage of disease and recurrence of prostate cancer in a high risk population? We initiated a community based study to educate and recruit African American men for early diagnosis of prostate cancer, that is the Detroit Education and Early Detection (DEED) study. Our objective was to evaluate our recruitment process for this target population, examine the percentage of organ confined prostate cancer in men undergoing radical prostatectomy and measure recurrence biochemically. MATERIALS AND METHODS: A community based study from February 1993 to February 1995 through the African American churches in metropolitan Detroit was initiated. We compared the early detection group treated with radical prostatectomy to the population presenting to our urological clinic during the same period. We tested and followed 1,105 African American men using the prostate specific antigen blood test. RESULTS: Pathologically organ confined prostate cancer was diagnosed in 11 of 17 men (65%) who underwent radical prostatectomy in the DEED project. Within the clinic population 35% of the African American men were diagnosed with pathologically organ confined prostate cancer. The difference between the 2 populations was statistically significant (p = 0.033). Disease recurred in 1 of 15 (7%) and 39 of 157 (25%) men in the DEED and clinic populations, respectively (p = 0.97). CONCLUSIONS: We demonstrated our ability to recruit African American men into a prostate cancer early detection program. We diagnosed early but clinically significant prostate cancers among African American men with characteristics similar to prostate cancers diagnosed in other early detection studies in which the overwhelming majority of men were white.

Aged↗
PubMed1996

Usage of antibacterial and antiparasitic drugs in animals in Sweden between 1988 and 1993.

The total usage of antibacterial and antiparasitic drugs in animals in Sweden between 1988 and 1993 was assessed. The data for the antibacterial drugs were divided among the different classes of drug used each year. Special attention was paid to the use of antibacterial drugs in feeding stuffs and to their use in pigs and fish. During the period studied, the total usage of antibacterial drugs remained stable at approximately 35 tonnes of active substance annually. The use of antibacterial drugs for growth-promoting purposes was prohibited in Sweden in 1986 and became available by veterinary prescription only. As a result the total amount used annually has decreased and stabilised at a level about 35 per cent lower than before the ban. Important changes during 1988 to 1993 were a doubled usage of tetracyclines and a 50 per cent decrease in the use of olaquindox. The five major classes of antibacterial drugs used in 1993 were benzyl penicillin (13.2 tonnes), tetracyclines (8.8 tonnes), olaquindox (3.5 tonnes), sulphonamides (2.0 tonnes) and aminoglycosides (1.9 tonnes). The total annual usage of coccidiostatic drugs, mainly used in the poultry industry, was stable at approximately 10 tonnes, while the usage of other antiparasitic drugs increased slightly to 7.7 tonnes.

Aminoglycosides↗
PubMed1995

Myogenic reactivity of coronary resistance arteries after cardiopulmonary bypass and hyperkalemic cardioplegia.

BACKGROUND: Cardiopulmonary bypass (CPB) and cardioplegia are associated with systemic hypotension and altered vascular responses, suggesting a defect in the smooth muscle control of vascular tone. Previous studies demonstrated alteration in neurohumoral control of the systemic and coronary circulation after CPB and cardioplegia; however, effects of CPB and cardioplegia on the intrinsic control of the vascular smooth muscle, especially in the coronary microcirculation, remain to be determined. METHODS AND RESULTS: Pigs were placed on CPB. Selected hearts were arrested with a cold, hyperkalemic ([K+] = 25 mmol/L) crystalloid cardioplegic solution for 1 hour. In another group, hearts were arrested and then reperfused with warm blood for 1 hour. Coronary arterioles (70 to 149 microns) were studied in a pressurized, no-flow state with video microscopy. Myogenic reactivity was examined to stepwise increases in intraluminal pressure from 10 to 100 mm Hg. The vessel diameter was normalized to the diameter at 50 mm Hg after application of papaverine (10(-4) mol/L). Myogenic reactivity of vessels from noninstrumented control pigs was not altered after mechanical denudation of the endothelium or pretreatment with NG-nitro-L-arginine or indomethacin. In vessels from control pigs and vessels from the CPB group, myogenic contraction was observed with pressures > 40 mm Hg. However, CPB significantly decreased intrinsic tone as the pressure-diameter relation shifted upward (P < .05 versus control). This decreased intrinsic tone was markedly attenuated by NG-nitro-L-arginine, suggesting an increased basal release of nitric oxide. Cardioplegic arrest, with or without reperfusion, decreased myogenic contraction to pressures > 40 mm Hg (P < .05 versus control). Pretreatment of vessels with glybenclamide normalized the cardioplegia-induced decrease in myogenic contraction (P < .05), suggesting that the reduced myogenic contraction is due to activation of ATP-sensitive potassium channels. CONCLUSIONS: The result of the present study suggests that coronary microvascular myogenic reactivity and the intrinsic tone are reduced after hyperkalemic cardioplegia and that CPB preserves myogenic reactivity but reduces the intrinsic tone of the vascular smooth muscle.

Animals↗
PubMed1995

Dating and context of three middle stone age sites with bone points in the Upper Semliki Valley, Zaire.

The extent to which the earliest anatomically modern humans in Africa exhibited behavioral and cognitive traits typical of Homo sapiens sapiens is controversial. In eastern Zaire, archaeological sites with bone points have yielded dates older than 89(-15)+22 thousand years ago by several techniques. These include electron spin resonance, thermoluminescence, optically stimulated luminescence, uranium series, and amino acid racemization. Faunal and stratigraphic data are consistent with this age.

Animals↗