Biomedical subjects

W Magee

Publications and source records attributed to W Magee.

10 recordsLinked to original sources

PubMed1998

Relative importance of adenosine A1 and A3 receptors in mediating physiological or pharmacological protection from ischemic myocardial injury in the rabbit heart.

Although ischemic preconditioning (IP) in several species can be pharmacologically mimicked by selective adenosine A1 or A3 receptor agonists, it is currently unclear which receptor subtype (A1 and/or A3) is physiologically involved in mediating IP. To investigate this question, we determined (a) the affinity of adenosine for rabbit adenosine A1 and A3 receptors, and (b) the effects of selective rabbit A1 receptor blockade on IP and adenosine-mediated cardioprotection in a rabbit Langendorff model of myocardial ischemia-reperfusion injury. Adenosine was 19-fold selective for inhibition of N6-(4-amino-3-[125I]iodobenzyl)adenosine (125I-ABA) binding to recombinant rabbit A1 v rabbit A3 receptors (A1 Ki: 28 nm; A3 Ki 532 nm). Buffer-perfused rabbit hearts were exposed to 30 min regional ischemia and 120 min of reperfusion, and infarct size was measured by tetrazolium staining and normalized for area-at-risk (IA/AAR). Ischemic preconditioning (5 min global ischemia and 10 min reperfusion) or adenosine (20 micro M, 5 min) perfusion reduced infarct size (IA/AAR) to 17+/-3 and 14+/-2%, respectively (controls: 59+/-2%). Ischemic preconditioning and adenosine-mediated cardioprotection were completely blocked (57+/-2 and 61+/-4% IA/AAR, respectively) in the presence of a rabbit A1-selective concentration (50 nm) of the antagonist BWA1433 (rabbit A1 Ki: 3 nm; A3 Ki; 746 n m). Thus, whereas recent studies have demonstrated that selective A1 or A3 receptor agonists can both pharmacologically mimic IP, the results of the present study suggest that the adenosine-mediated component of IP in the isolated rabbit heart is preferentially mediated by adenosine A1 receptors, potentially due to adenosine's selectivity for this receptor subtype.

Adenosine↗

PubMed1998

Selective activation of adenosine A3 receptors with N6-(3-chlorobenzyl)-5'-N-methylcarboxamidoadenosine (CB-MECA) provides cardioprotection via KATP channel activation.

OBJECTIVE: The aim of this study was to characterize the adenosine A3 receptor agonist, N6-(3-chlorobenzyl)-5'-N-methylcarboxamidoadenosine (CB-MECA), evaluate its ability to reduce myocardial ischemia/reperfusion injury and determine the role of KATP-channel activation in A3 receptor-mediated cardioprotection. METHODS: Binding affinities and adenylate cyclase inhibition were examined in CHO cells expressing rabbit recombinant adenosine A1 or A3 receptors. Infarct size (normalized for area-at-risk; % IA/AAR) was measured in buffer-perfused rabbit hearts exposed to 30-min regional ischemia and 120 min of reperfusion. RESULTS: CB-MECA was 100-fold selective for A3 vs. A1 receptors (A3 Ki: 1 nM; A1 Ki: 105 nM). Five-min perfusion with CB-MECA before ischemia/reperfusion elicited a concentration-dependent reduction in infarct size (EC50: 0.3 nM). The CB-MECA-dependent cardioprotection (control: 58 +/- 2; CB-MECA: 21 +/- 3% IA/AAR) was unchanged by an A1-selective concentration of the antagonist, BWA1433, but was completely prevented (P < 0.05) by a nonselective (A1/A3) concentration (55 +/- 6% IA/AAR). The KATP channel inhibitors, glibenclamide and 5-HD, had no effect on control infarct size, yet significantly (P < 0.05) blunted the CB-MECA-dependent cardioprotection (glibenclamide: 49 +/- 6; 5-HD: 58 +/- 4% IA/AAR). CONCLUSIONS: CB-MECA is a novel 100-fold A3 receptor-selective agonist which should prove useful for elucidating A3-dependent mechanisms in the rabbit heart. Selective stimulation of adenosine A3 receptors with CB-MECA reduces myocardial ischemia/reperfusion injury via a mechanism which involves activation of KATP channels.

Adenosine↗

PubMed1997

Selective adenosine A3 receptor stimulation reduces ischemic myocardial injury in the rabbit heart.

OBJECTIVE: The aim of this study was to determine whether selective activation of the adenosine A3 receptor reduces infarct size in a Langendorff model of myocardial ischemia-reperfusion injury. METHODS: Buffer-perfused rabbit hearts were exposed to 30 min regional ischemia and 120 min of reperfusion. Infarct size was measured by tetrazolium staining and normalized for area-at-risk (IA/AAR). RESULTS: Preconditioning by 5 min global ischemia and 10 min reperfusion reduced infarct size (IA/AAR) to 19 +/- 4% (controls: 67 +/- 5%). Replacing global ischemia with 5 min perfusion of the rabbit A3-selective agonist, IB-MECA (A3 Ki: 2 nM; A1 Ki: 30 nM) elicited a concentration-dependent reduction in infarct size; 50 nM IB-MECA reduced IA/AAR to 24 +/- 4%. The A1-selective agonist, R-PIA (25 nM) reduced IA/AAR to a similar extent (21 +/- 6%). However, while the cardioprotective effect of R-PIA was significantly inhibited (54 +/- 7% IA/AAR) by the rabbit A1-selective antagonist, BWA1433 (50 nM), the IB-MECA-dependent cardioprotection was unaffected (28 +/- 6% IA/AAR). A non-selective (A1 vs. A3) concentration of BWA1433 (5 microM) significantly attenuated the IB-MECA-dependent cardioprotection (61 +/- 7% IA/AAR). CONCLUSIONS: These data clearly demonstrate that selective A3 receptor activation provides cardioprotection from ischemia-reperfusion injury in the rabbit heart. Furthermore, the degree of A3-dependent cardioprotection is similar to that provided by A1 receptor stimulation or ischemic preconditioning.

Adenosine↗

PubMed1997

One-stage reconstruction for defects caused by cancrum oris (noma).

Cancrum oris is a disease process that has been described for centuries, but now presents primarily in developing countries. The disease in known to occur in association with poor nutrition and exanthematous infections. The acute disease occurs usually in young children, and the infectious process causes destruction of the involved orofacial tissues with variable degrees of tissue loss and scar reaction in those who are affected and survive. The chronic sequelae of the acute disease process often require reconstructive surgery. We present the natural history of the disease process and its causes, and demonstrate the wide spectrum of resulting defects that challenge the reconstructive surgeon. Because of the socioeconomic situation inherent with these patients and the volume of patients in need of treatment with this disease, innovative and efficient treatment is required. We have demonstrated methods of reconstructive surgery that differ from the multiple staged procedures described in previous studies by allowing for one-stage surgical reconstruction of even the most complex cases. This allows for treatment of the majority of patients in their native countries in a cost-effective and safe manner, and treatment of more severely afflicted individuals in modern medical centers without their having to spend a long time period away from their homes.

Adult↗

PubMed1997

Studies of the candidate genes TGFB2, MSX1, TGFA, and TGFB3 in the etiology of cleft lip and palate in the Philippines.

Population-based candidate-gene studies can be an effective strategy for identifying genes involved in the etiology of disorders where family-based linkage studies are compromised by lack of access to affected members, low penetrance, and/or genetic heterogeneity. We evaluated association data for four candidate genes using a population from the Philippines that is genetically separate from previously studied Caucasian populations. Case ascertainment was made possible by collaboration with Operation Smile, a volunteer medical organization, which facilitated identification of a large number of cases for study. A new allelic variant of transforming growth factor-beta 3 was identified to use in these studies. After exclusion of syndromic cases of cleft lip and palate, no evidence for association with previously reported allelic variants of transforming growth factor-beta 2 (TGFB2), homeobox 7 (MSX1), or transforming growth factor-alpha (TGFA), or with the new TGFB3 variant was detected. Previous association studies using Caucasian populations of nonsyndromic cleft lip and/or palate (CL/P) and cleft palate only (CPO) have strongly suggested a role for TGFA in the susceptibility of clefting in humans. Exclusion of significant association in a non-Caucasian population for TGFA suggests that TGFA plays less of a role than it does in Caucasians. This may be due to multiple or different genetic and/or environmental factors contributing to the etiology of this most common cranio-facial anomaly in the Philippine population.

Alleles↗

PubMed1997

Clinical and epidemiologic studies of cleft lip and palate in the Philippines.

Clinical and epidemiologic studies of defined geographic populations can serve as a means of establishing data important for genetic counseling and as a first step in identifying strategies best suited for identification of causes. Under the sponsorship of Operation Smile International, clinical, genetic, and epidemiologic studies were carried out at six sites within the Philippines between 1989 and 1996. Patients who were being evaluated for surgical repair of craniofacial anomalies (primarily clefts of the lip and palate) were briefly examined for the presence of associated anomalies, and a family history was obtained to look for the frequency of cleft lip and palate in siblings. Birth records of 47,969 newborns over an 8-year period at one hospital in Bacolod City in the province of Negros Occidental were reviewed. Medical records of infants born with clefts of the lip and/or palate and other major anomalies were reviewed and birth prevalence rates calculated. Findings include a birth prevalence of 1.94 per 1000 live births for cleft lip with/without palate in the Philippines. Recurrence rates in siblings for nonsyndromic clefts of the lip and palate were 23 per 1000 for cleft lip with or without cleft palate, and 14 per 1000 for cleft palate only. The percentage of clefts associated with multiple anomalies was 21% at birth and 6% for individuals examined during the screening process, providing evidence for a high postnatal death rate. These data provide groundwork for additional etiologic studies including segregation analysis and molecular genetic studies involving linkage or association, as well as for studies of environmental contributions to clefting such as vitamin deficiencies. Preliminary molecular analysis using an association approach is reported in a companion paper. The findings suggest a high incidence of cleft lip and palate in native-born Filipinos.

Abnormalities, Multiple↗

PubMed1995

The effect of very early cleft palate closure on the need for ventilation tubes in the first years of life.

The otologic consequences associated with cleft palates are well known. Closure of palatal clefts within the first weeks of life has many potential benefits, including improved feeding and cosmesis. The potential otologic benefits of very early closure are not known. Eighteen newborns have undergone closure of their palatal clefts within the first month of life with subsequent otolaryngology follow-up through our craniofacial center. Thirteen (72%) of the 18 still required placement of ventilation tubes during their first 3 years of life because of persistent effusion (for more than 120 days) or recurrent infection (more than four episodes in 6 months or more than six episodes in 12 months). Very early cleft palate closure may not significantly alter the need for ventilation tubes in children with palatal clefts.

Cleft Palate↗

PubMed1994

Postnatal testing for unusual genodermatoses.

A wide variety of unusual genodermatoses may be encountered by physicians during training or later in their practice. We have briefly described some of these and have outlined laboratory studies that may aid in their diagnosis.

Albinism↗

PubMed1988

Use of a latissimus dorsi myocutaneous flap for closure of an orocutaneous fistula of the cheek.

The latissimus dorsi myocutaneous flap can be used successfully for external cover in the cheek region when the nature of the defect precludes the use of other local or regional flaps. It is exceedingly useful when a large amount of well-vascularized tissue is needed. The flap is extremely reliable and versatile as a one-stage reconstruction. Its major drawbacks are its bulkiness and the necessity to reposition the patient intraoperatively.

Back↗

PubMed1975

Biology of infections of split thickness skin grafts.

The purpose of this study was to identify determinants of split thickness skin graft infection. The bacterial count of the experimental wounds was proportional to the incidence of infection in split thickness skin grafts. When the wound was heavily contaminated with 107 organisms, infection developed under most grafts. Graft take frequently occurred in wounds subjected to a lower level of inoculum. The importance of bacterial counts as a determinant of potential skin graft infection was also suggested by a clinical study. We now routinely use quantitative bacterial counts to identify the granulating wounds that are ready for grafting. The type of organism played no significant role in the development of infection.

Animals↗