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Biomedical subjects

Michael Shannon

Publications and source records attributed to Michael Shannon.

At least 19 recordsLinked to original sources
PubMed2007

Early predictors of mortality in hemodynamically unstable pelvis fractures.

OBJECTIVES: To determine reliable, early indicators of mortality and causes of death in hemodynamically unstable patients with pelvic ring injuries. DESIGN: This was a retrospective review of a prospective pelvic database. METHODS: In all, 187 hemodynamically unstable patients with pelvic fractures (persistent systolic blood pressure <90 mm Hg after receiving 2 L of intravenous crystalloid) admitted from April 1998 to November 2004 were included. Intervention was Level 1 Trauma Center-Pelvis Fracture standardized protocol. Main outcome measurements were: Injury Severity Score (ISS), Revised Trauma Score (RTS), age, blood transfusion, mortality, and multisystem organ failure (MOF). RESULTS: Group 1 (39 patients) did not survive their injury. Group 2 (148 patients) survived their injury. Fracture pattern (chi(2) = 9.1, P = 0.33), and treatment with angiography/embolization (chi(2) = 0.054, P = 0.84) were not predictive of death. Patients requiring more blood had a statistically significant higher mortality rate. The ISS (t = -5.62, P < 0.001), RTS (t = 6.10, P < 0.001), age >60 years old (chi(2) = 5.4, P = 0.03), and transfusion (t = -2.70, P = 0.010) were statistically significant independent predictors of mortality. A logistic regression analysis and receiver operating characteristic curves indicated that of these variables, RTS was the most predictive independent variable. However, a model including all four variables was superior at predicting mortality. Most deaths were attributed to exsanguination (74.4%) or MOF (17.9%). CONCLUSIONS: Predictors of mortality in pelvis fracture patients should be available early in the course of treatment in order to be useful. Death within 24 hours was most often a result of acute blood loss while death after 24 hours was most often caused by MOF. Improved survival will depend upon the evolution of early hemorrhage control and resuscitative strategies in patients at high mortality risk.

Aged↗
PubMed2006

Understanding the degradation pathway of a poorly water-soluble drug formulated in PEG-400.

VX-497 is a poorly water-soluble compound. It is formulated in PEG-400 and encapsulated in softgel capsules. Although the drug product is stable at refrigerated conditions, many degradation peaks have been observed at accelerated storage conditions. An investigation utilizing high performance liquid chromatography-mass spectrometry (HPLC-MS) was conducted to understand the degradation mechanism of the active pharmaceutical ingredient (VX-497) in PEG-400 formulation. Results revealed that the degradation was mainly caused by the reaction between VX-497 with moisture (hydrolysis) and PEG-400 (PEGylation). The numerous degradation peaks observed in the samples stored at accelerated conditions were PEG adducts covalently attached to portions of the VX-497 molecule, which were confirmed by comparison with synthetic markers. Investigation also found that an impurity, which was present in the VX-497 drug substance, reacted with PEG-400 following the same reaction mechanism, and generated additional impurities in the VX-497 drug product. By changing the process for drug substance synthesis, pure batches of VX-497 were obtained. Furthermore, it was found that the reaction between VX-497 and PEG-400 was temperature and time dependent. When the drug product was manufactured at 45 degrees C and the processing time was controlled, the PEG degradants and by-products were reduced to non-detectable levels, resulting in greatly improved drug product quality. This paper presents an integrated effort among analytical, process, and formulation scientists on how to develop a better drug product by understanding the fundamental issues of the drug product, namely the degradation mechanism.

Capsules↗
PubMed2006

Building a trauma center and system in Tuscany, Italy.

BACKGROUND: Growing evidence supports the premise that adult trauma centers lower the risk of death for severely injured patients. The same principles have been applied to the pediatric population and mounting research suggests that, as in the adult population, gravely injured children have better outcomes at pediatric trauma centers where personnel trained and experienced in the specific needs and unique physiology of injured children provide care. As in the United States, acute traumatic injury represents an important public healthcare concern to the Tuscan regional government whose goal is to maximize clinical outcomes within available resources. In order to address this problem, the Tuscan regional government has created a new and innovative collaboration between the Meyer Pediatric Hospital/University of Florence School of Medicine and the Children's Hospital Boston/Harvard Medical School to build a pediatric trauma center and regional pediatric trauma referral system. GOALS AND OBJECTIVES: This long-term international initiative will seek to develop a demonstration model for pediatric trauma care that may later be replicated elsewhere. The initial goals of the project will focus on expanding the role of the pediatricians working in the emergency department to include the acute care of medical, surgical, orthopedic and multiple trauma patients. This new configuration will closely resemble the single provider model of emergency medical care commonly utilized in the United States. During this transition period to a more broadly trained emergency physician, a multi-disciplinary trauma team will be created and pediatric trauma clinical practice guidelines will be introduced into the emergency department and inpatient care units. Systems measurements will be achieved through a comprehensive quality improvement and risk management program. Ultimately, all Tuscan regional pediatric major trauma will be consolidated at the Meyer Pediatric Hospital in Florence.

Boston↗
PubMed2005

Bench to bedside: Pharmacogenomics, adverse drug interactions, and the cytochrome P450 system.

As physicians attempt to improve the quality of health care, one area of particular concern has been preventable medical errors from adverse drug interactions. The cytochrome P450 family of enzymes has been implicated in a large number of these preventable, adverse drug interactions. This report reviews the basic biochemistry and pharmacogenomics underlying the reactions catalyzed by the cytochrome P450 family of enzymes. An emphasis is placed on the phenotypic variations within a population and the resulting clinical effects. In addition, six members of the cytochrome P450 superfamily that are responsible for the metabolism of the majority of pharmaceutical agents are profiled in detail. These enzymes, CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2, are reviewed with regard to their phenotypic variation in the population and the resulting clinical and therapeutic implications.

Adolescent↗
PubMed2005

Use of hemoglobin raffimer for postoperative life-threatening anemia in a Jehovah's Witness.

PURPOSE: To describe the successful treatment of acute, life-threatening anemia with the oxygen therapeutic agent, hemoglobin (Hb) raffimer. CLINICAL FEATURES: A 53-yr-old female Jehovah's Witness developed severe anemia following total hip replacement. Due to prior patient directive, red blood cells were not transfused. Tachycardia, hypotension, electrocardiographic abnormalities and mental status changes developed with a nadir Hb concentration of 3.2 g x dL(-1). Hb raffimer is a purified, cross-linked, human Hb solution developed as a substitute for red blood cell Hb. After obtaining informed consent as well as Food and Drug Administration and Institutional Review Board approval for compassionate use, 2 L of Hb raffimer (Hemolink, Hemosol, Inc., Toronto, ON, Canada) were administered along with ferrous sulfate and epoetin alfa therapy. The patient's Hb level rose to 5.5 g x dL(-1) with resolution of symptoms. To allow recovery of red blood cell mass while maintaining Hb level > 4.5 g x dL(-1), additional 1000 mL doses of Hb raffimer were administered on postoperative days three, five and seven (total dose = 500 g Hb). The patient developed no serious adverse events related to treatment with Hb raffimer. By postoperative day 14, the patient's Hb level increased to 6.5 g x dL(-1) with a hematocrit of 23%. The patient was discharged. CONCLUSIONS: Use of Hb raffimer as a bridge to recovery of this patient's red blood cell mass may have prevented adverse clinical outcome. Because this product is a purified Hb solution devoid of other cellular components, it may be accepted as therapy by patients who, due to religious conviction, refuse allogeneic red blood cell transfusion.

Anemia↗
PubMed2005

The Internet and psychoactive substance use among innovative drug users.

OBJECTIVE: The Internet contains an extraordinary amount of information on the recreational use of psychoactive substances. We investigated the effect of the Internet on the drug-use knowledge, attitudes, and behaviors of adolescents. METHODS: Cross-sectional survey of adolescents being managed for substance abuse. RESULTS: Of 12 patients (9 male, 3 female) who had used the Internet to learn about psychoactive substances, 100% reported that Internet-based information had affected the ways in which they had used psychoactive substances. Of the 12 respondents, 8 described adopting behaviors intended to minimize the risks associated with psychoactive substance use. Respondents also reported changes in the use of a wide variety of illicit substances as well as over-the-counter and prescription pharmaceuticals. Examiners assessed whether quotations demonstrated that respondents' knowledge, attitudes, and behaviors toward psychoactive substance use were affected by Internet information. Despite the subjective nature of the research question, there was a highly significant agreement between coders. CONCLUSIONS: Web-based data on psychoactive substances seem to influence a broad range of drug-use behaviors in adolescents. Information on the ways that the Internet is being used by this vulnerable population should be considered in the design of Web sites to prevent the initiation and use of psychoactive substances.

Adolescent↗
PubMed2005

Infant methemoglobinemia: the role of dietary nitrate in food and water.

Infants for whom formula may be prepared with well water remain a high-risk group for nitrate poisoning. This clinical report reinforces the need for testing of well water for nitrate content. There seems to be little or no risk of nitrate poisoning from commercially prepared infant foods in the United States. However, reports of nitrate poisoning from home-prepared vegetable foods for infants continue to occur. Breastfeeding infants are not at risk of methemoglobinemia even when mothers ingest water with very high concentrations of nitrate nitrogen (100 ppm).

Humans↗
PubMed2004

A multidisciplinary approach to restoring an acquired palatal defect using distraction osteogenesis: a clinical report.

Prosthetic and surgical procedures can be applied to rehabilitate acquired palatal defects. Distraction osteogenesis may be used to narrow the defect to facilitate bone and soft tissue closure. This clinical report describes a multidisciplinary approach to the closure of a palatal defect with distraction osteogenesis, comprehensive orthodontic treatment, surgical soft tissue flap reconstruction of the residual soft tissue defect, implant placement in the newly created edentulous ridge, and restoration with an implant-supported prosthesis.

Adult↗
PubMed2004

Effects of 4-methylpyrazole on ethanol neurobehavioral toxicity in CD-1 mice.

OBJECTIVES: 4-Methylpyrazole (4-MP), an alcohol dehydrogenase (ADH) antagonist, is used for the treatment of ethylene glycol and methanol ingestions. However, ethanol is frequently co-ingested by those who ingest these more toxic alcohols. Several in vitro and in vivo studies have shown a decrease in the elimination rate of ethanol after the administration of 4-MP, but none has evaluated the effects of 4-MP administration on the neurobehavioral toxicity of ethanol. This was a study to determine whether ADH blockade with 4-MP prolongs ethanol neurobehavioral toxicity in a murine model. METHODS: D-1 mice were pretreated with 4-MP, with observation of its effect on ethanol dose-response curves. 4-MP (25 mg/kg) or an equal volume of saline was administered intraperitoneally. Ten minutes later, incremental ethanol doses of 1-5 g/kg were administered intraperitoneally. Pretreated and control groups were composed of ten mice each for each dose of ethanol tested. Outcomes for assessing ethanol neurobehavioral toxicity were successful performance on the rotarod test and presence of the righting reflex, two established and validated outcome measures for ethanol-induced neurobehavioral toxicity in mice. RESULTS: The dose of ethanol at which 50% of the animals failed a particular outcome test (toxic dose 50 [TD(50)]) was decreased with 4-MP administration for both the rotarod test and the righting reflex. The TD(50) intergroup differences (control vs. 4-MP) were statistically significant at 60, 120, and 180 minutes (p < 0.05). CONCLUSIONS: Pretreatment with 4-MP significantly prolonged ethanol neurobehavioral toxicity in CD-1 mice, presumably by inhibiting its metabolism by ADH. Further investigation is warranted to evaluate this interaction.

Alcohol-Induced Disorders, Nervous System↗
PubMed2004

Efficacy of an educational Web site for educating physicians about bioterrorism.

OBJECTIVES: To determine whether a Web-based educational intervention improves emergency physicians' knowledge about bioterrorism and to survey physicians' knowledge and sources of information on bioterrorism. METHODS: Prospective randomized controlled trial using pre- and postintervention testing in hospitals. Participants were general and pediatric emergency medicine attending physicians, fellows, and fourth-year emergency medicine residents. All participants completed a pretest and attended a lecture on bioterrorism. Participants were then randomized to the Web intervention group that received continuous access to a bioterrorism educational Web site with weekly exposure to case scenarios of diseases due to biological agents, or the control group. Participants were retested after one and six months and surveyed to identify their sources of information and assess their knowledge. RESULTS: Sixty-three physicians completed the pretest. There was no difference in mean +/- standard deviation (SD) pretest scores between Web intervention (45% +/- 10%) and control (44% +/- 10%) groups (mean difference: 1.9%; 95% confidence interval [CI] = -6.7% to 2.9%). There was no significant difference between pre- and posttest scores among groups at one month (Web intervention 48% +/- 10% vs. control 45% +/- 10%; mean difference: 3.3%; 95% CI = -8.5% to 2.0%) and six months (Web intervention 51% +/- 8% vs. control 47% +/- 9%; mean difference: 3.8%; 95% CI = -8.8% to 1.2%). More than 60% of physicians cited media reports as their primary source of information on bioterrorism and believed that their knowledge of bioterrorism was limited after one month. CONCLUSIONS: Providing physicians information on bioterrorism through simulated cases and continuous access to an educational Web site does not increase knowledge of bioterrorism. Physicians are more likely to use media reports for their primary source of information.

Attitude of Health Personnel↗
PubMed2003

Use of HTR synthetic bone as an augmentation material in conjunction with immediate implant placement: a case report.

Immediate placement of dental implants (DI) in fresh extraction sockets is associated with remaining voids around the DI and often a partial dehiscence or thin facial alveolar plate. Bioplant HTR synthetic bone (HTR) was used as a ridge preservation/augmentation material in conjunction with this method of DI placement. A 61-year-old white woman requiring extraction of tooth 12 opted for immediate DI placement. HTR was used to fill the remaining socket void and enhance the facial ridge width, and primary closure was attempted with sutures. DI uncovering was performed at about 6 months. Measurements were taken to the nearest 0.5 mm of the internal socket width and total site width at DI placement and uncovering. The internal socket width was essentially maintained (6.8 vs 6.6 mm), and the total ridge width showed a change from 8.7 to 9.1 mm. The results of this case suggest that HTR is a useful adjunct in the placement of immediate DIs for the preservation of ridge width.

Alveolar Ridge Augmentation↗