Biomedical subjects

Matthew C Davis

Publications and source records attributed to Matthew C Davis.

5 recordsLinked to original sources

PubMed2006

Use of thromboelastograph and factor VII for the treatment of postoperative bleeding in a pediatric patient on ECMO after cardiac surgery.

This report describes a case of possibly fatal bleeding treated successfully with an "overdose" of recombinant factor VII (rFVII; Novo7). A 3.5-year-old boy had surgery for aortic stenosis and aortic arch repair and was placed on extracorporeal membrane oxygenation (ECMO) after a prolonged cardiopulmonary bypass time (CPB); there was subsequent failure to wean from CPB because of right ventricular failure. Subsequently, a severe coagulopathy developed, and despite large volume transfusions with blood and blood products, this was unresolved. Thromboelastograph (TEG) measurements were obtained, and on the advice of the Hematology Department, Novo7 (recommended dose: 15-30 microg/kg) was administered at a dose of 200 microg/kg because of the severity of the bleeding. TEG was repeated, and a further dose of Novo7 was administered at 500 microg/kg; a further TEG after 15 minutes showed normalization, and the remaining bleeding was treated surgically. The patient was weaned from ECMO 48 hours later and was subsequently discharged home with no further problems. Novo7 in an "overdose" can apparently correct major coagulopathy even in patients on ECMO support with no dire effects on the ECMO circuit or the patient in a life-threatening scenario.

Aorta, Thoracic↗

PubMed2005

Are we improving after 10 years of humanitarian paediatric cardiac assistance?

BACKGROUND: Paediatric cardiovascular services are frequently absent or poorly developed in many countries around the world. Our foundation made 83 trips in support of cardiovascular services between April 1993 and March 2003 to help alleviate this problem. In this study, we present an analysis of our results over these period of 10 years. METHODS: We performed a review of all available records relating to the trips, including patient databases, audited financial statements, donated product inventory lists, lists of team members, and follow-up data from the host sites concerning the state of the patients treated. RESULTS: We made 83 trips to 14 countries, 40 of these being in Central Europe, 5 in Eastern Europe, 10 in Caribbean, and Central America, 18 in South America, 9 in Asia, and 1 in the Middle East. In the first 5 years, we made 23, as opposed to 60 in the second 5 years, this difference being significant (p less than 0.01). The total number of primary operations performed over 10 years was 1,580. The number of procedures performed yearly increased over the two intervals from 97.0 plus or minus 32.7 to 219.0 plus or minus 41.7, p less than 0.002. The probability of survival between the periods increased from 84.6 to 93.3 per cent, and this was also significantly different (p less than 0.001). Overall, the rate of survival for the period of 10 years was 90.5 per cent. Moreover, the value of services donated to support each trip also differed significantly, decreasing from 105,900 dollars plus or minus 14,581 dollars for the first period to 54,617 dollars plus or minus 11,425 dollars for the second period (p less than 0.001). CONCLUSIONS: Improving paediatric cardiac services in under-served countries requires significant financial and personnel commitments, but can produce reasonable outcomes.

Altruism↗

PubMed2004

Synthesis and biological evaluation of novel curcumin analogs as anti-cancer and anti-angiogenesis agents.

A series of novel curcumin analogs were synthesized and screened for anti-cancer and anti-angiogenesis activities at Emory University and at the National Cancer Institute (NCI). These compounds are symmetrical alpha,beta-unsaturated and saturated ketones. The majority of the analogs demonstrated a moderate degree of anti-cancer activity. Compounds 10, 11, and 14 exhibited a high degree of cytotoxicity in the NCI in vitro anti-cancer cell line screen. In addition, this screen revealed that these compounds inhibit tumor cell growth with a higher potency than the commonly used chemotherapeutic drug, cisplatin. In independent in vitro screens conducted at Emory, the same compounds plus 4, 5, 8, 9, and 13 exhibited a high degree of cytotoxicity to tumor cells. Analogs that were effective in the anti-cancer screens were also effective in in vitro anti-angiogenesis assays. Compounds 4, 9, 11, and 14 were most effective in the anti-angiogenesis assays run at Emory. In the assays conducted by the NCI, compound 14 was almost as potent as the anti-angiogenic drug TNP-470, which has undergone clinical trials. Based on the favorable in vitro anti-cancer and anti-angiogenesis results with 14, further in vivo tests were conducted. This compound effectively reduced the size of human breast tumors grown in female athymic nude mice and showed little toxicity. This data, coupled with the remarkable in vitro data, suggests that compound 14 may potentially be an effective chemotherapeutic agent. As a follow-up, a 3D quantitative structure relationship based on 14 has been developed. It shows a cross-validated r2(q2) and a predictive r2(p2) = 0.71. COMPARE analysis suggests the compound to be a possible RNA/DNA antimetabolite, but also implies that the compound's cytotoxicity may arise from a presently unknown mechanism.

Angiogenesis Inhibitors↗

PubMed2002

Expansion of structure-activity studies of piperidine analogues of 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine (GBR 12935) compounds by altering substitutions in the N-benzyl moiety and behavioral pharmacology of selected molecules.

A series of substituted N-benzyl analogues of the dopamine transporter (DAT) specific compound, 4-[2-(diphenylmethoxy)ethyl]-1-benzylpiperidine were synthesized and biologically characterized. Different 4'-alkyl, 4'-alkenyl, and 4'-alkynyl substituents were introduced in the phenyl ring of the benzyl moiety along with the replacement of the same phenyl ring by the isomeric alpha- and beta-naphthyl groups. Different polar substitutions at the 3'- and 4'-position were also introduced. Novel compounds were tested for their binding affinity at the dopamine, serotonin, and norepinephrine transporter systems in the brain by competing for [(3)H]WIN 35 428, [(3)H]citalopram, and [(3)H]nisoxetine, respectively. Selected compounds were also evaluated for their activity in inhibiting the uptake of [(3)H]dopamine. Binding results demonstrated that alkenyl and alkynyl substitutions at the 4'-position produced potent compounds in which compound 6 with a vinyl substitution was the most potent. In vivo evaluation of three selected compounds indicated that despite their high potency at the DAT, these compounds stimulated locomotor activity (LMA) less than cocaine when tested across similar dose ranges. In a drug discrimination study procedure, none of these three compounds generalized from cocaine in mice trained to discriminate 10 mg/kg cocaine from vehicle. In a 4 h time course LMA experiment, one of our previous lead piperidine derivatives (1a) showed considerable prolonged action. Thus, in this report, we describe a structure-activity relationship study of novel piperidine analogues assessed by both in vitro transporter assays and in vivo behavioral activity measurements.

Animals↗

PubMed2002

Sealer distribution in coronal dentin.

A major cause of tooth discoloration is sealer remnants in the pulp chamber after root canal treatment. The purpose of this study was to assess coronal distribution and color changes of four commonly used sealers placed in the pulp chamber after 2 yr. Fifty extracted premolars were cross-sectioned in the coronal third of the root. The chamber contents were removed, and instrumentation was via the canal; then freshly mixed sealer was placed in each chamber. Sealers evaluated were: AH 26, Kerr Pulp Canal Sealer, Roth 801, and Sealapex. The apical access was sealed with white sticky wax, and the tooth was maintained in a moist environment at 37 degrees C for 2 yr. Teeth were split longitudinally, and digital images of the exposed dentin were made, scrambled, and evaluated blindly by trained evaluators for color changes and for presence of sealer in dentin. There was no measurable penetration of sealer into dentin for all groups and no dentin discoloration occurred. The sealers displayed marked discoloration. At 2 yr, the sealers discolored and remained confined primarily to the pulp chamber.

Bismuth↗