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Biomedical subjects

C Breen

Publications and source records attributed to C Breen.

At least 19 recordsLinked to original sources
PubMed2004

Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence.

BACKGROUND: Buprenorphine has recently been reported to be an alternative to methadone and LAAM for maintenance treatment of opioid dependent individuals, differing results are reported concerning its relative effectiveness indicating the need for an integrative review. OBJECTIVES: To evaluate the effects of buprenorphine maintenance against placebo and methadone maintenance in retaining patients in treatment and in suppressing illicit drug use. SEARCH STRATEGY: We searched the following databases up to 2001, inclusive: Cochrane Drugs and Alcohol Review Group Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Current Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol and Drug Council of Australia (ADCA) [www.adca.org.au], Australian Drug Foundation (ADF -VIC) [www.adf.org.au], Centre for Education and Information on Drugs and Alcohol (CEIDA) [www.ceida.net.au], Australian Bibliographic Network (ABN), and Library of Congress databases, available NIDA monographs and the College on Problems of Drug Dependence Inc. proceedings, the reference lists of all identified studies and published reviews and authors of identified RCT's were asked about any other published or unpublished relevant RCT. SELECTION CRITERIA: Randomised clinical trials of buprenorphine maintenance compared with either placebo or methadone maintenance for opioid dependence. DATA COLLECTION AND ANALYSIS: Reviewers evaluated the papers separately and independently, rating methodological quality of concealment of allocation; data were extracted independently for meta-analysis and double-entered. MAIN RESULTS: Thirteen studies met the inclusion criteria, all were randomised clinical trials, all but one were double-blind. The method of concealment of allocation was not clearly described in 11 of the studies, otherwise methodological quality was good. Buprenorphine given in flexible doses appeared statistically significantly less effective than methadone in retaining patient in treatment (RR= 0.82; 95% CI: 0.69-0.96). Low dose buprenorphine is not superior to low dose methadone. High dose buprenorphine does not retain more patients than low dose methadone, but may suppress heroin use better. There was no advantage for high dose buprenorphine over high dose methadone in retention (RR=0.79; 95% CI:0.62-1.01), and high dose buprenorphine was inferior in suppression of heroin use. Buprenorphine was statistically significantly superior to placebo medication in retention of patients in treatment at low doses (RR=1.24; 95% CI: 1.06-1.45), high doses (RR=1.21; 95% CI: 1.02-1.44), and very high doses (RR=1.52; 95% CI: 1.23-1.88). However, only high and very high dose buprenorphine suppressed heroin use significantly above placebo. REVIEWERS' CONCLUSIONS: Buprenorphine is an effective intervention for use in the maintenance treatment of heroin dependence, but it is not more effective than methadone at adequate dosages.

Buprenorphine↗
PubMed2002

Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence.

BACKGROUND: Buprenorphine has recently been reported to be an alternative to methadone and LAAM for maintenance treatment of opioid dependent individuals, differing results are reported concerning its relative effectiveness indicating the need for an integrative review. OBJECTIVES: To evaluate the effects of buprenorphine maintenance against placebo and methadone maintenance in retaining patients in treatment and in suppressing illicit drug use. SEARCH STRATEGY: We searched the following databases up to 2001, inclusive: Cochrane Drugs and Alcohol Review Group Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Current Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol and Drug Council of Australia (ADCA) [www.adca.org.au], Australian Drug Foundation (ADF -VIC) [www.adf.org.au], Centre for Education and Information on Drugs and Alcohol (CEIDA) [www.ceida.net.au], Australian Bibliographic Network (ABN), and Library of Congress databases, available NIDA monographs and the College on Problems of Drug Dependence Inc. proceedings, the reference lists of all identified studies and published reviews and authors of identified RCT's were asked about any other published or unpublished relevant RCT. SELECTION CRITERIA: Randomised clinical trials of buprenorphine maintenance compared with either placebo or methadone maintenance for opioid dependence. DATA COLLECTION AND ANALYSIS: Reviewers evaluated the papers separately and independently, rating methodological quality of concealment of allocation; data were extracted independently for meta-analysis and double-entered. MAIN RESULTS: Thirteen studies met the inclusion criteria, all were randomised clinical trials, all but one were double-blind. The method of concealment of allocation was not clearly described in 11 of the studies, otherwise methodological quality was good. Buprenorphine given in flexible doses appeared statistically significantly less effective than methadone in retaining patient in treatment (RR= 0.82; 95% CI: 0.69-0.96). Low dose buprenorphine is not superior to low dose methadone. High dose buprenorphine does not retain more patients than low dose methadone, but may suppress heroin use better. There was no advantage for high dose buprenorphine over high dose methadone in retention (RR=0.79; 95% CI:0.62-1.01), and high dose buprenorphine was inferior in suppression of heroin use. Buprenorphine was statistically significantly superior to placebo medication in retention of patients in treatment at low doses (RR=1.24; 95% CI: 1.06-1.45), high doses (RR=1.21; 95% CI: 1.02-1.44), and very high doses (RR=1.52; 95% CI: 1.23-1.88). However, only high and very high dose buprenorphine suppressed heroin use significantly above placebo. REVIEWER'S CONCLUSIONS: Buprenorphine is an effective intervention for use in the maintenance treatment of heroin dependence, but it is not more effective than methadone at adequate dosages.

Buprenorphine↗
PubMed2002

Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence.

BACKGROUND: Methadone maintenance was the first widely used form of opioid replacement therapy developed to treat heroin dependence, and it remains the best-researched treatment for this problem. Despite the widespread use of methadone in maintenance treatment for opioid dependence in many countries, it is a controversial treatment whose effectiveness has been disputed. OBJECTIVES: To evaluate the effects of methadone maintenance treatment (MMT) compared with treatments that did not involve opioid replacement therapy (i.e., detoxification, offer of drug-free rehabilitation, placebo medication, wait-list controls) for opioid dependence. SEARCH STRATEGY: We searched all the following databases up to 2001: Cochrane Drugs and Alcohol Review Group Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Current Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol and Drug Council of Australia (ADCA) [www.adca.org.au], Australian Drug Foundation (ADF-VIC) [www.adf.org.au], Centre for Education and Information on Drugs and Alcohol (CEIDA) [www.ceida.net.au], Australian Bibliographic Network (ABN), and Library of Congress databases, available NIDA monographs and the College on Problems of Drug Dependence Inc. proceedings, the reference lists of all identified studies and published reviews; authors of identified RCTs were asked about other published or unpublished relevant RCTs. SELECTION CRITERIA: All randomised controlled clinical trials of methadone maintenance therapy compared with either placebo maintenance or other non-pharmacological therapy for the treatment of opioid dependence. DATA COLLECTION AND ANALYSIS: Reviewers evaluated the papers separately and independently, rating methodological quality of concealment of allocation, data were extracted independently for meta-analysis and double-entered. MAIN RESULTS: Six studies met the criteria for inclusion in this review, all were randomised clinical trials, two were double-blind. There were a total number of 954 participants. The method of concealment of allocation was inadequate in one study, not clearly described in four studies, but adequate in a sixth study. Based on the meta-analysis, methadone appeared statistically significantly more effective than non-pharmacological approaches in retaining patient in treatment (3 RCTs, RR=3.05; 95%CI: 1.75-5.35) and in the suppression of heroin use (3 RCTs, RR=0.32; 95%CI: 0.23-0.44), but not statistically in criminal activity (3 RCTs, RR=0.39; 95%CI: 0.12-1.25). REVIEWER'S CONCLUSIONS: Methadone is an effective maintenance therapy intervention for the treatment of heroin dependence as it retains patients in treatment and decreases heroin use better than treatments that do not utilise opioid replacement therapy. It does not show a statistically significant superior effect on criminal activity.

Humans↗
PubMed2001

Interferon gamma and prostaglandin in BSE-infected cattle.

Suspect field cases of BSE infection (displaying clinical signs) were examined for possible alterations of cytokine/autacoid plasma levels and were compared to control cases (not displaying clinical signs of BSE infection). Interferon gamma (IFN-gamma) plasma levels were demonstrated as being elevated in all suspected field cases of BSE infection (irrespective of BSE status; determined via postmortem histopathological examination). We demonstrated that plasma IFN-gamma levels were significantly (P<0.005) higher in suspect cases of BSE infection than in control cases. BSE-positive prostaglandin-E(2), (PGE(2)) plasma levels were demonstrated as being elevated 1.25-fold above BSE-negative cases and 2.22-fold above control cases. No significant (P>0.5) increase in PGE(2)plasma levels was recorded between BSE-positive and -negative. IFN-gamma and PGE(2)plasma levels were examined using commercially available ELISA assay. The results presented in this publication are the first demonstration of alteration in immune state in animals with BSE.

Animals↗
PubMed2001

Withdrawal from methadone maintenance treatment: prognosis and participant perspectives.

OBJECTIVE: To determine the proportion of clients engaged in methadone maintenance treatment who have favourable prognosis for withdrawal, and to examine client perceptions and expectations of withdrawal. METHODS: A broad cross-section of 856 methadone clients was sampled across Melbourne, Sydney and Brisbane. Self-complete surveys were developed for the clients, their clinic staff or pharmacists, and methadone prescribers. The client survey examined aspects of the clients' perspectives of withdrawal, and the surveys for the service providers collected information about each client's current treatment episode. Informed consent was provided by clients to obtain information from their clinic staff member or pharmacist, and their methadone prescriber. RESULTS: Most clients (70%) were at least very interested in methadone withdrawal. Clients were also more optimistic about their own post-withdrawal outcomes (in terms of opioid use) than both their clinic staff and prescribing doctors. Clinical criteria indicated that 31% of clients had a reasonable prognosis for withdrawal. However, when considering all factors, 17% had good withdrawal prognosis, were interested in methadone withdrawal, and believed it was very likely they would remain opioid-free for three months post-withdrawal. CONCLUSIONS: Despite the likely continued increase in client numbers in substitution maintenance treatment, the majority of methadone clients have a poor prognosis for withdrawal and should not be encouraged to cease treatment. IMPLICATIONS: Clients who do not meet key clinical criteria are likely to have poor clinical outcomes regardless of how withdrawal is attempted.

Adult↗
PubMed2001

Implementing a data warehouse at Inglis Innovative Services.

Data warehouses, data marts, and data mining have been hot topics in the 1990s, offering the promise of a vault of corporate data ripe for decision making. As is true with all promising technologies, the key issue is how to get started. Implementation of a corporate data warehouse involves a lot more than spending a huge amount of money on hardware, software, and consultants. Successful implementation of a data warehouse involves a corporate treasure hunt--identifying and cataloging data. It involves data ownership, data integrity, and business process analysis to determine what the data are, who owns them, how reliable they are, and how they are processed. Finally, implementation of the warehouse drives the issue of how good the decisions are that are based on the information in the warehouse. This article presents a case study of how one healthcare facility dealt with the challenges of implementing a data warehouse.

Computer Communication Networks↗
PubMed1999

Circumcision and neonatal tetanus: disclosure of risk and its reduction by topical antibiotics.

BACKGROUND: Previous case-control studies have paradoxically suggested that circumcisions protect against neonatal tetanus (NNT), but these observations have not been adjusted for differences in the length of survival of cases and controls. METHODS: Boy cases (n = 133) and their sex-matched controls (n = 399) were extracted from a population-based study of NNT undertaken in Punjab Province, Pakistan. In the resulting file, circumcisions were censored such that analysis was restricted to only those that occurred before onset in cases or before age of onset in the matched case for controls. The effect of topical antibiotics in circumcision wounds was then evaluated. RESULTS: After adjusting for confounders, circumcision before onset posed a significant risk for NNT (matched odds ratio [OR] = 3.1, 95% CI: 1.2-8.0). The risk of NNT in those circumcised before onset and treated with topical antibiotics did not differ significantly from the referent group who had not been circumcised before onset (matched OR = 1.1, 95% CI: 0.2-6.8), whereas the lack of topical use was associated with significant risk (matched OR = 4.2, 95% CI: 1.4-12.6). This suggests that topical antibiotics are likely to be highly effective in preventing NNT from circumcision wounds. We estimated an overall risk of about 16 fatal NNT cases per 1000 live boy births with circumcision wounds that were not protected by topical antibiotics, and that circumcision and umbilical wounds each accounted for about half of this overall risk in these boys. CONCLUSIONS: Topical antibiotics should be routinely applied to all wounds created by traditional circumcisions, to prevent NNT and sepsis from these frequently unsterile procedures.

Administration, Topical↗
PubMed1999

Pharmacokinetics of novel erythropoiesis stimulating protein compared with epoetin alfa in dialysis patients.

Novel erythropoiesis stimulating protein (NESP) is a hyperglycosylated analogue of recombinant human erythropoietin (Epoetin) which has an increased terminal half-life in animal models. The aim of this study was to extend these observations to humans. Using a double-blind, randomized, cross-over design, the single-dose pharmacokinetics of Epoetin alfa (100 U/kg) and an equivalent peptide mass of NESP were compared following intravenous bolus in 11 stable peritoneal dialysis patients. This was followed by an open-label study to determine the single-dose pharmacokinetics of an equivalent peptide mass of NESP by subcutaneous injection in six of these patients. The mean terminal half-life for intravenous NESP was threefold longer than for intravenous Epoetin (25.3 versus 8.5 h), a difference of 16.8 h (95% confidence interval, 9.4 to 24.2 h, P = 0.0008). The area under the serum concentration-time curve was significantly greater for NESP (291.0 +/- 7.6 ng x h per ml versus 131.9 +/- 8.3 ng x h per ml; mean +/- SEM; P < 0.0005), and clearance was significantly lower (1.6 +/- 0.3 ml/h per kg versus 4.0 +/- 0.3 ml/h per kg; mean +/- SEM; P < 0.0005). The volume of distribution was similar for NESP and Epoetin (52.4 +/- 2.0 ml/kg versus 48.7 +/-2.1 ml/kg; mean +/-SEM). The mean terminal half-life for subcutaneous NESP was 48.8 h. The peak concentration of subcutaneous NESP was approximately 10% of that following intravenous administration, and bioavailability was approximately 37% by the subcutaneous route. The longer half-life of NESP is likely to confer a clinical advantage over Epoetin by allowing less frequent dosing in patients treated for anemia.

Adult↗
PubMed1999

Inhibition of CFU-E colony formation in uremic patients with inflammatory disease: role of IFN-gamma and TNF-alpha.

BACKGROUND: There is evidence for the role of inflammatory cytokines in the inhibition of erythropoiesis in the anemia of chronic disease, but the extent to which they contribute to resistance to erythropoietin (EPO) in patients with chronic renal failure is not clear. The purpose of the present study was to assess the effect of sera from patients with end-stage renal failure with and without infection or inflammatory disease on CFU-E colony formation in vitro. METHODS: Bone marrow was obtained from uremic patients with inflammatory disease and from healthy controls. Standard colony assays were used to assess erythroid colony formation (CFU-E) in response to EPO in the presence or absence of 5% autologous serum. Normal bone marrow mononuclear cells were cultured with 5% v/v sera from three groups of patients: healthy volunteers, uremic controls, and uremic patients with inflammatory disease. RESULTS: There was no difference between normal and uremic bone marrow response to EPO. However, when uremic/inflammatory bone marrow was cultured with autologous serum the optimal response to EPO was significantly inhibited. Optimal CFU-E colony formation was suppressed significantly by sera from either uremic group when compared with cultures containing sera from controls. Treatment of parallel cultures with a combination of antibodies to interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) almost completely restored the response to EPO. Additionally, bone marrow from healthy controls incubated with uremic sera showed an increased production of interleukin-1 alpha (IL-1 alpha) and IFN-gamma, and TNF-alpha was present in uremic sera. CONCLUSIONS: CFU-E colony formation is inhibited by soluble factors present in the sera of uremic patients with or without inflammatory disease. These soluble factors stimulate the production of IFN-gamma and TNF-alpha, which directly inhibit erythropoiesis at a local level in the bone marrow.

Adult↗
PubMed1998

Polycation-Exchanged Clays as Sorbents for Organic Pollutants: Influence of Layer Charge on Pollutant Sorption Capacity.

The uptake curves for the adsorption of a polycation ([CH2CH(OH)CH2N(CH3)2]n+n(Cl)n-n) onto a low iron Texas bentonite, WL, have been determined and compared with those onto two source smectites, SWy-1 and SAz-1. The polycation exhibited a marked affinity for all the smectite surfaces but polycation uptake was maximized on the fine fractions of Na+-WL. Variable temperature X-ray diffraction of the clay polycation complexes showed that the polycation was segregated into different interlayers at loadings below 30% of the CEC. The adsorption of benzene onto TMA+-exchanged SWy-1, SAz-1, and WL showed that, despite having a comparable layer charge to SWy-1, WL was as poor a sorbent for benzene as SAz-1, which has a much higher layer charge. The adsorption of p-nitrophenol (PNP) from aqueous solution onto the TMA+-exchanged sorbents exhibited the same trends, although a smaller amount was adsorbed due to the greater size of PNP. The amount of PNP adsorbed by polycation-treated SWy-1 depended upon the polycation loading, and PNP uptake maximized at loadings of 28 and 46 mg (g clay)-1. At higher loadings (80, 102, and 147 mg (g clay)-1) the uptake curves became linear and the PNP uptake decreased with increased polycation loading. No polycation-treated clay was as effective as TMA+-exchanged SWy-1 for the removal of PNP from water. Copyright 1998 Academic Press.

Journal Article↗
PubMed1997

Adsorption of Polycations on Clays: A Comparative in situ Study Using 133Cs and 23Na Solution Phase NMR

23Na solution phase NMR has been evaluated as an in situ probe to study the adsorption of tetramethylammonium (TMA+) and two polycations, FL17 ([(Me2NCH2CHOHCH2)n]n+Cln) and Magnafloc 1697, ([(CH2CHCH2N(Me)2CH2&Cmacr;HCH2)n]n+Cln), onto clays in aqueous suspensions containing 2.5 mass% low iron Texas bentonite. The NMR data shows the effectiveness of the organocations at displacing Na+ from the bentonite surface. This information has been correlated with that obtained from particle-size and electrophoretic measurements in aqueous solution, together with information from adsorption isotherms. These results have been compared to those obtained in parallel studies using 133Cs solution phase NMR. FL17 and 1697 both exhibited high affinity adsorption isotherms on Na+- and Cs+-clay, whereas the adsorption of TMA+, which represents the cationic portion of the polymers was of lower affinity. Na+-bentonite adsorbed almost twice the amount of polycation required to fulfill the cation-exchange capacity (CEC) of the bentonite. The electrophoretic and particle size data indicated significant differences in the size of the polycation/clay flocs and the amount of polymer adsorbed on the external faces of the flocs in the presence of Na+- and Cs+-exchange ions. Correlation of this data with the NMR results suggests that the Na+-bentonite/polycation flocs are large, of low density, and that the polycation is concentrated in the interior while the Na+-ions occupy exchange sites on the external faces. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗
PubMed1996

Hospital admission following ambulatory surgery.

BACKGROUND: Ambulatory surgery continues to grow in quantity and complexity of procedures. Effective measures of "quality" are not readily apparent. "Unplanned admission rate" may well reflect the quality of care in this area. Identifying factors related to this event could be helpful in quality assessment and improvement. METHODS: A review of all unplanned admissions for a 3-year period in a University-affiliated teaching hospital. RESULTS: An overall rate of 0.85% (129/15,132) was observed. Rate varies by specialty and no one procedure was at higher risk. Pain control, cardiopulmonary, and bleeding problems as well as larger than anticipated procedures accounted for 73% of the admissions. CONCLUSIONS: Unplanned admission following ambulatory surgery is relatively rare but could reflect overall quality in terms of the system, physician, and patient. Comparisons between institutions and within institution requires defining key demographic elements whose identification for now remains a challenge.

Aged↗
PubMed1996

Invasive cervical cancer in Southampton and South West Hampshire: effect of introducing a comprehensive screening programme.

A study of invasive cervical cancer in Southampton and South West Hampshire is reported, covering three consecutive three year periods during which the screening coverage increased from an estimated 60% to a recorded 87% of eligible women aged 20-64. From the first to the third periods of the study in that age group registrations of fully invasive squamous cell carcinoma (stage lb and above) fell from 64 to 30 (53%), which was largely counteracted by an increase in microinvasive squamous cell carcinoma (linear trend: P<0.0001). In the same age group registrations of adenocarcinoma rose slightly, which resulted from an increase in the number diagnosed at a depth of invasion of less than 3 mm. There were no significant changes in the numbers of stage III and IV cancers or among cancers in women aged 65 and over. A strong inverse association was found between stage of both histological types of cancer and their likelihood of being screen detected rather than symptomatic: 91% of screen detected cancers were diagnosed at stage I compared with 38% of symptomatic cancers. There was a slight downward trend in the incidence of cancer per 100,000 total female population across the three periods of the study with a significant trend towards low stage disease, which is likely to reduce mortality in years to come. The trend towards screen detected cancers and cancers of less than 3 mm depth of invasion is presented as a positive outcome to be expected in early rounds of increasing the screening coverage.

Adenocarcinoma↗
PubMed1996

Relation between the incidence of invasive cervical cancer and the screening interval: is a five year interval too long?

OBJECTIVE: To examine the incidence of invasive cervical cancer per 100,000 women years at risk and relative risk according to screening history among eligible women aged 25-69 in Southampton and South West Hampshire during the three years after completion of the first round of comprehensive screening. RESULTS: There was a significantly higher incidence of invasive cervical cancer in women who had not been screened during the preceding 0.5-5.5 years than in those who had been screened (relative risk (RR) 2.6; 95% confidence interval (CI) 1.6 to 4.3). Among the latter group of women (with interval cancers) there was a significantly higher incidence in those with a long interval of 3.5-5.5 years since their most recent smear than in those with a short interval of 0.5-3.5 years (RR 2.2; 95% CI 1.3 to 3.8). Among women with non-interval cancers, there was a significantly higher incidence among those who had no cytology record than among those who had been screened but were overdue for a smear (RR 3.0; 95% CI 1.2 to 7.3). When screen detected cancers were excluded from the figures the relative risks for all the comparative groups described above were greater, though the 95% confidence limits were wider because the numbers were smaller. The most pronounced difference in incidence was between symptomatic cancers in women with a short screening interval (5.8 per 100,000 women years at risk) and in women with no cytology record (71.3 per 100,000 years at risk). Most cancers were interval cancers (76%) because of the high screening coverage: 89.2% of eligible women aged 25-69 had been screened during the preceding 0.5-5.5 years. The overall incidence per 100000 women years at risk approached that of interval cancers, and was nearer to that observed in the short than the long interval because 74.7% of women had been screened within 3.5 years. CONCLUSION: The results confirm the effectiveness of screening but suggest that a five year screening interval may be too long, at least during the early rounds of screening.

Adult↗
PubMed1991

Neonatal macular hemorrhage.

Retinal hemorrhages occur with increased frequency in neonates following prolonged or difficult labor, especially if associated with primipara, surgical or mechanical intervention, low Apgar scores, perinatal hypoxia, low birth weight or coagulopathy. When involvement occurs peripheral to the arcades resolution occurs generally without sequelae. Hemorrhages involving the macula are much more serious since resolution in these cases may result in degenerative changes or an exudative or glial scar, resulting in amblyopia and possible strabismus. Early examination is warranted in high-risk infants in order to facilitate intervention and the prevention of more serious visual sequelae.

Adult↗
PubMed1990

Scanning electron microscopy of corneal incisions using steel, diamond, and sapphire blades.

In order to compare the wound morphology they produce, we used steel (Myocure), diamond (CILCO DK 121), and sapphire (Katena K2-6500) blades, to make parallel linear incisions, 500 microns deep, in 12 fresh enucleated porcine eyes. There was no discernible difference among the blades in terms of either the morphology of the collagen lamellae of the sides or the depth of the incisions produced. The major differences in the cuts produced were attributable primarily to the differences in the footplates.

Animals↗
PubMed1989

Ductus arteriosus: involvement of a sarcolemmal cytochrome P-450 in O2 constriction?

Our previous studies implicate a cytochrome P-450-based mechanism in the constrictor response of the ductus arteriosus to oxygen. The present experiments were conducted on saponin-skinned strips of ductal muscle from mature fetal lambs to determine the location, sarcolemmal versus intracellular, of this cytochrome and to obtain a better insight into the sequence of events underlying the action of oxygen. Skinned preparations contracted to free Ca2+ over the range between 0.1 and 5-10 microM (pCa 7 to 5). In contrast, oxygen (PO2, 608-690 Torr; 1 Torr = 133.3 Pa) had no significant effect, both in the absence and presence of 10 microM calcium. Carbon monoxide, tested as pure CO or a CO-O2 mixture (ratio 0.28), did not relax preparations maximally contracted with calcium. These findings indicate that oxygen exerts its effect on the plasma membrane of ductus muscle cells and that a membrane-bound cytochrome P-450 mechanism likely functions as the signal transducer for oxygen in the formation of a constrictor agent.

Animals↗