Biomedical subjects

Alan T Davis

Publications and source records attributed to Alan T Davis.

13 recordsLinked to original sources

PubMed2006

The effect of traumatic brain injury upon the concentration and expression of interleukin-1beta and interleukin-10 in the rat.

BACKGROUND: Using a model of traumatic brain injury (TBI) in the rat, this study was undertaken to characterize the short-term biochemical changes of IL-1beta, IL-10, and tumor necrosis factor TNF-alpha to determine whether injury in the brain elicits a systemic cytokine response. METHODS: Sprague-Dawley rats were subjected to a TBI using a weight-drop model and then killed at various time points after injury. Samples of blood, brain, and liver were recovered and analyzed for concentrations of IL-1beta, IL-10, and TNF-alpha as well as IL-1beta and IL-10 mRNA expression in liver and brain. RESULTS: In brain, IL-1beta increased in the first hour after injury, peaked at 8 hours, and declined during the final 16 hours. IL-10 quickly increased during the first 4 hours and then gradually rose over the last 20 hours. Analysis of liver showed no upregulation of these markers and plasma IL-1beta and IL-10 were unchanged compared with controls. Although not upregulated in brain, TNF-alpha showed a statistically significant (p < 0.05) rise in plasma from 14 +/- 16 pg/mL at 20 minutes to 91 +/- 28 pg/mL at 24 hours. CONCLUSION: Using a model of TBI, we have demonstrated that there is a rise in both IL-1beta and IL-10 in the injured rat brain within the first 24 hours after injury without a corresponding rise in either plasma or liver. Therefore, it appears as if two strong indicators of brain injury severity are expressed and possibly carry out their actions solely in the brain.

Animals↗

PubMed2006

Radiation exposure in trauma patients.

BACKGROUND: Trauma patients are exposed to a large amount of ionizing radiation. Radiologic examinations may include a multitude of plain films, computed tomography scans, and/or fluoroscopic examination. Previous studies have assessed radiation exposure to staff members at trauma centers, and in pregnant trauma patients. The purpose of the current study is to evaluate the amount of radiation to which trauma patients are exposed in a Level I trauma center. METHODS: The study used a prospective cohort design. All patients for whom a trauma code was activated between the months of September 2004 and July of 2005 were eligible to be enrolled in the study. Upon arrival to the trauma bay, a dosimeter badge, that measures ionizing radiation, was attached to a Velcro bracelet on the wrist of the patient. The badges were removed at the time of discharge from the hospital and analyzed. RESULTS: Data were collected on 224 patients (167 adults, 57 pediatric). The median amount of radiation exposure to all patients equaled 68 MREM (Interquartile range 31-181). A significant increase in the median amount of radiation exposure was found in patients with orthopedic injuries (107 MREM vs. 45 MREM), an Injury Severity Score (ISS) >15 (107 MREM vs. 46 MREM), a length of stay >than 1 week (105 MREM vs. 65 MREM), age >18 (82 MREM vs. 44 MREM), and when >11 radiologic procedures were performed (127 MREM vs. 46 MREM). CONCLUSION: Trauma patients are being exposed to high amounts of radiation. Patients with orthopedic injuries, and those more severely injured, are at an increased risk. Further precautions to limit radiation exposure in this population are needed.

Adult↗

PubMed2005

In cerebrospinal fluid ER chaperones ERp57 and calreticulin bind beta-amyloid.

The beta-amyloids (abetas) are the major components of the plaque observed in the brains of patients with Alzheimer's disease. The conundrum is that although they are produced in everyone during the posttranslational processing in the endoplasmic reticulum (ER) of the amyloid precursor protein (APP), deposits are only observed in the elderly. Our work suggests that normals have a carrier protein(s) keeping them in solution. Based on immunoblotting studies of cerebrospinal fluid (CSF) from normals, we find that the bulk of the abetas are bound to the ER chaperones, ERp57 and calreticulin, suggesting that these may be carrier proteins which prevent aggregation of the abetas and that the deposits are due to faulty ER posttranslational processing of APP with the failure to form this complex. If membrane protein synthesis is similarly affected, it could explain the neuronal dysfunction characteristic of Alzheimer's disease.

Aging↗

PubMed2005

Recombinant factor VIIa for the treatment of severe postoperative and traumatic hemorrhage.

BACKGROUND: The aim of this study was to determine the dose of recombinant factor VIIa (rFVIIa) that has been used in our institution to successfully control hemorrhage in trauma and postoperative patients. METHODS: This was an 8-month retrospective cohort study of 13 patients with acute hemorrhage and no known history of coagulopathic disorders. RESULTS: Administration of factor VIIa resulted in the cessation of life-threatening hemorrhage at dosages approximately one half those recommended for the management of hemophilia. After administration, there was a significant decrease in the total blood-product transfusion requirement (P <0.05). CONCLUSIONS: The use of factor VIIa in patients with life-threatening hemorrhage is a safe and effective therapeutic modality when used as an adjunct to standard interventions for control of severe hemorrhage. Lower-dose regimens were as successful as higher-dose regimens previously reported. The results of this respective study of 13 patients suggests that recombinant factor VIIa therapy for control of life-threatening hemorrhage as an adjunct to standard interventions can be successful at doses <90 mg/kg.

Adult↗

PubMed2005

Early tracheostomy versus late tracheostomy in the surgical intensive care unit.

BACKGROUND: This study's purpose was to determine if early tracheostomy (ET) of severely injured patients reduces days of ventilatory support, the frequency of ventilator-associated pneumonia (VAP), and surgical intensive care unit (SICU) length of stay (LOS). METHODS: This 2-year retrospective review included 185 SICU patients with acute injuries requiring mechanical ventilation and tracheostomy. ET was defined as 7 days or less, and late tracheostomy (LT) as more than 7 days. RESULTS: The incidence of VAP was significantly higher in the LT group, relative to the ET group (42.3% vs. 27.2%, respectively; P <.05). Acute Physiology and Chronic Health Evaluation II scores, hospital and SICU LOS, and the number of ventilator days were significantly higher in the LT group. CONCLUSIONS: In patients who required prolonged mechanical ventilation, there was significant decreased incidence of VAP, less ventilator time, and lower ICU LOS when tracheostomy was performed within 7 days after admission to the SICU.

Adolescent↗

PubMed2005

Carnitine deficiency and supplementation do not affect the gene expression of carnitine biosynthetic enzymes in rats.

Starved male weanling rats supplemented with 20 mmol/L pivalate in their drinking water exhibit significantly depressed concentrations of carnitine in tissues and plasma. In addition, pivalate supplementation has been linked with increased renal and hepatic trimethyllysine hydroxylase (TMLH) activity, whereas carnitine supplementation has been associated with significantly decreased hepatic gamma-butyrobetaine hydroxylase (BBH) activity. The purpose of this study was to determine whether pivalate or carnitine supplementation affects the activity and genetic expression of 2 enzymes of carnitine (Cn) biosynthesis, TMLH and BBH, expressed as mRNA abundance, relative to the abundance of beta-actin mRNA. Male weanling rats were administered the control treatment (C; n = 6), the pivalate treatment (P; n = 7), or the pivalate treatment plus supplemental dietary carnitine (P+Cn; n = 7). Rats in group P had elevated renal TMLH activity, relative to the other groups (P < 0.05). The groups did not differ in the abundance of renal or hepatic TMLH or BBH mRNA. A previously unreported finding was the quantifiable level of renal BBH mRNA, which was verified by direct sequencing of the BBH cDNA product amplified from kidney RNA. The groups did not differ in renal BBH mRNA abundance and renal BBH enzyme activity was not detected. Thus, the alterations in enzyme activities in the pivalate-treated rats are not regulated at the transcriptional level, and are apparently related to post-transcriptional effects on the enzymes themselves.

Animals↗

PubMed2004

Animate advanced laparoscopic courses improve resident operative performance.

BACKGROUND: The use of animate training laboratories have been touted as an important part of a surgical resident's training. This study determines if there was any benefit in resident performance and whether that benefit persisted. METHODS: Twelve senior surgical residents attended a course in advanced laparoscopy with didactic and laboratory components. The residents' skills were tested by having them perform a laparoscopic fundoplication before, immediately after, and 6 months after the course. The procedure was videotaped, and divided into stages that were timed and scored by a single, masked observer. RESULTS: Overall performance score was 35.7 +/- 2.5 for the pretest, improving to 16.5 +/- 1.2 (P <0.05) immediately after the course, and 23.7 +/- 5.1 (P <0.05) at 6 months. Significant improvements were seen with trocar insertion, crural closure, division of short gastric arteries, and fundoplication. CONCLUSIONS: The data presented demonstrate significant and persistent improvement in laparoscopic operative skills as a result of focused laboratory skill training.

Adult↗

PubMed2004

Induction of apoptosis by antisense CK2 in human prostate cancer xenograft model.

Protein serine/threonine kinase CK2 (formerly casein kinase 2) is a ubiquitous protein kinase that plays key roles in cell growth, proliferation, and survival. We have shown previously that its molecular down-regulation induces apoptosis in cancer cells in culture. Here, we have employed a xenograft model of prostate cancer to extend these studies to determine whether antisense CK2alpha evokes a similar response in vivo. A single dose of antisense CK2alpha oligodeoxynucleotide given directly into the PC3-LN4 xenograft tumor in nude mouse induced a dose- and time-dependent tumor cell death in vivo. The tumor was completely resolved at the higher tested dose of the antisense. Cell death was due to apoptosis and correlated with a potent down-regulation of the CK2alpha message and loss of CK2 from the nuclear matrix in the xenograft tissue as well as in cancer cells in culture. These observations accorded with several of the earlier studies indicating that loss of CK2 from the nuclear matrix is associated with induction of apoptosis. Comparison of the effects of antisense CK2alpha oligodeoxynucleotide on cancer versus normal or noncancer cells showed that the concentration of antisense CK2alpha that elicited extensive apoptosis in tumor cells in culture or xenograft tumors in vivo had a relatively small or minimal effect on noncancer cells in culture or on normal prostate gland subjected to orthotopic injection of antisense oligodeoxynucleotide in vivo. The basis for the difference in sensitivity of cancer versus noncancer cells to antisense CK2alpha is unknown at this time; however, this differential response under similar conditions of treatment may be significant in considering the potential feasibility of targeting the CK2 signal for induction of apoptosis in cancer cells in vivo. Although much further work will be needed to establish the feasibility of targeting CK2 for cancer therapy, to our knowledge, this is the first report to provide important new evidence as an initial "proof of principle" for the potential application of antisense CK2alpha in cancer therapy, paving the way for future detailed studies of approaches to targeting CK2 in vivo to induce cancer cell death.

Animals↗

PubMed2003

Cell cycle dependent regulation of protein kinase CK2 signaling to the nuclear matrix.

Protein kinase CK2 is a ubiquitous protein serine/threonine kinase that is involved in cell growth and proliferation as well as suppression of apoptosis. Several studies have suggested that the kinase plays a role in cell cycle progression; however, changes in enzyme activity during phases of cell cycle have not been detected. Nuclear matrix is a key locus for CK2 signaling in the nucleus. We therefore examined CK2 signaling to the nuclear matrix in distinct phases of cell cycle by employing synchronized ALVA-41 prostate cancer cells. Removal of serum from the culture medium resulted in G0/G1 arrest, and a reduction in the nuclear matrix-associated CK2 activity which was rapidly reversed on addition of serum. Arresting the cells in G(0)/G(1) phase with hydroxyurea and subsequent release to S phase by serum gave similar results. Cells arrested in the G(2)/M phase by treatment with nocodazole demonstrated an extensive reduction in the nuclear matrix-associated CK2 which was reversed rapidly on addition of serum. Changes in the immunoreactive CK2 protein were concordant with the activity data reflecting a dynamic trafficking of the kinase in distinct phases of cell cycle. Under the same conditions, CK2 activity in total cellular lysate remained essentially unaltered. These results provide the first direct evidence of discrete modulations of CK2 in the nuclear matrix during the cell cycle progression. Inducible overexpression of CK2 in CHO cells yielded only a modest increase in CK2 activity even though a significant increase in expression was apparent at the level of CK2 alpha-specific message. Stably transfected ALVA-41 cells, however, did not show a significant change in CK2 levels despite increased expression at the message level. Not surprisingly, both types of the stably transfected cells failed to show any alteration in cell cycle progression. Distribution of the CK2 activity in the cytosolic versus nuclear matrix fractions in normal cells appears to be different from that in the cancer cells such that the ratio of nuclear matrix to cytosolic activity is much higher in the latter. Considering that nuclear matrix is central to several nuclear functions, this pattern of intracellular distribution of CK2 may have implications for its role in the oncogenic process. Published 2003 Wiley-Liss, Inc.

Animals↗

PubMed2002

Heat shock mediated modulation of protein kinase CK2 in the nuclear matrix.

Nuclear matrix, a key structure in the nuclear framework, appears to be a particularly responsive target during heat shock treatment of cells. We have previously shown that nuclear matrix is a preferential target for protein kinase CK2 signaling in the nucleus. The levels of CK2 in the nuclear matrix undergo dynamic changes in response to altered growth status in the cell. Here, we have demonstrated that CK2 targeting to the nuclear matrix is profoundly influenced by treatment of the cells to temperatures higher than 37 degrees C. Rapid increase in the nuclear matrix association of CK2 is observed when cells are placed at temperatures of 41 and 45 degrees C. This effect at 45 degrees C was higher than at 41 degrees C, and was time-dependent. Also, different cell lines behaved in a qualitatively similar manner though the quantitative responses differed. The modulations in the nuclear matrix associated CK2 in response to heat shock appear to be due to trafficking of the enzyme between cytosolic and nuclear compartments. In addition, it was noted that isolated nuclei subjected to heat shock also responded by a shuttling of the intrinsic CK2 to the nuclear matrix compartment. These results suggest that modulations in CK2 in the nuclear compartment in response to the heat stress occur not only by a translocation of the enzyme from the cytoplasmic compartment to the nuclear compartment, but also that there is a redistribution of the kinase within the nuclear compartment resulting in a preferential association with the nuclear matrix. The results support the notion that CK2 association with the nuclear matrix in response to heat shock may serve a protective role in the cell response to stress.

Casein Kinase II↗

PubMedDate not supplied

A randomized trial of endoscopic and fluoroscopic placement of postpyloric feeding tubes in critically ill patients.

BACKGROUND: Early postpyloric feeding is considered the accepted method of nutrition support in critically ill patients. Endoscopic and fluoroscopic techniques are associated with the highest percentage of successful placement. The purpose of this study was to compare endoscopic vs fluoroscopic placement of postpyloric feeding tubes in critically ill patients. METHODS: This is a randomized prospective clinical trial. Forty-three patients were randomized to receive feeding tubes by endoscopic or fluoroscopic technique. All procedures were performed at the bedside in the critical care unit. A soft small-bore nonweighted feeding tube was used in all cases. Successful placement was confirmed by either an abdominal x-ray for endoscopic technique or a fluoroscopic radiograph for fluoroscopic technique. RESULTS: Postpyloric feeding tubes were successfully placed in 41 of 43 patients (95%). The success rate using endoscopic technique was 96% (25 of 26), whereas the rate using fluoroscopy was 94% (16 of 17). The average time of successful placement was 15.2 +/- 2.9 (mean +/- SEM) minutes for endoscopic placement and 16.2 +/- 3.2 minutes for fluoroscopic placement, which was not statistically significant (p > .05). CONCLUSIONS: Endoscopic and fluoroscopic placement of postpyloric feeding tubes can safely and accurately be performed at the bedside in critically ill patients. Our results showed no significant difference in the success rate or time of placement between endoscopic vs fluoroscopic placement of postpyloric feeding tubes.

Critical Care↗

PubMedDate not supplied

Hyperemesis gravidarum and fetal outcome.

BACKGROUND: Hyperemesis gravidarum (HG) is reported in 0.5-2% of all pregnancies. The purpose of this research was to evaluate the relationship of maternal HG, neonatal birth weight, and birth outcomes. METHODS: This is a prospective cohort study of 45 patients diagnosed, by Fairweather's criteria, with HG compared with 306 non-HG control pregnant patients with singleton pregnancies. Sociodemographic and clinical data were obtained from the pregnant patients. Neonatal data were also collected, including indicators of neonatal wellness. RESULTS: Significantly higher incidences of being nonwhite (33% vs 16%; p < .05) and of attaining post-high school education (60% vs 38%) were noted in the HG group, relative to controls. Mothers in the control group experienced greater gestational weight gain, 14.9 +/- 0.3 kg (mean +/- SEM) relative to mothers in the HG group (10.6 +/- 1.3 kg). Infants from HG pregnancies manifested significantly lower birth weight (3.23 +/- 0.09 kg vs 3.52 +/- 0.03 kg), younger gestational age (38.4 +/- 0.3 weeks vs 39.7 +/- 0.1 weeks), and a greater length of hospital stay (2.9 +/- 0.5 days vs 1.8 +/- 0.1 day), relative to infants from the control group. After undergoing multivariate analysis, HG was a significant predictor of decreased gestational age and increased hospital length of stay. CONCLUSIONS: Infants born of women who had HG are more likely to experience decreased gestational age and increased length of hospital stay. Efficacy of early and aggressive treatment of HG, including nutrition support, in minimizing these outcomes needs to be studied.

Adult↗

PubMedDate not supplied

Carnitine treatment improved quality-of-life measure in a sample of Midwestern hemodialysis patients.

BACKGROUND: Previously, we demonstrated that selected groups of hemodialysis patients might be more likely to have abnormalities of carnitine metabolism. The purpose of the present study was to examine the effects of carnitine therapy in these selected groups of hemodialysis patients on quality-of-life measures and erythropoietin dose. METHODS: This was a double-blind, randomized, controlled trial, in which 50 hemodialysis patients were treated with either 2 g i.v. carnitine or placebo. The treatment period was for 24 weeks. RESULTS: Thirty-four patients (15 in the treatment group) completed the study. The mean age was 69 +/- 15 years, 35% were women, and 44% had diabetes. Mean initial plasma total, free, short-chain acyl and long-chain acyl carnitine concentrations (micromol/L; mean +/- SEM) were 35.9 +/- 1.8, 18.2 +/- 1.1, 11.6 +/- 0.6, and 6.0 +/- 0.3, whereas the plasma acyl-to-free-carnitine ratio was 1.02 +/- 0.05. With respect to the Medical Outcomes Short Form-36 (SF-36), improvements from baseline were noted in the treatment group (n = 13) for role-physical (33.9 +/- 1.9 to 43.2 +/- 3.0, p < .05) and the SF-36 physical component summary score (36.1 +/- 2.7 to 39.7 +/- 2.3, p = .09) relative to changes in the control group (n = 14). The erythropoietin dose over the 24-week period was reduced from baseline in the treatment group relative to the placebo group (-1.62 +/- 0.91 vs 1.33 +/- 0.79 units erythropoietin/dry weight/hemoglobin concentration, respectively, p < .05). CONCLUSIONS: After 24 weeks of i.v. carnitine therapy, SF-36 scores were improved and erythropoietin doses were reduced in hemodialysis patients, relative to the control group.

Aged↗