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Biomedical subjects

W Garrett

Publications and source records attributed to W Garrett.

At least 19 recordsLinked to original sources
PubMed2003

IL-1 beta induces COX2, MMP-1, -3 and -13, ADAMTS-4, IL-1 beta and IL-6 in human tendon cells.

Overuse injuries and trauma in tendon often involve acute or chronic pain and eventual matrix destruction. Anti-inflammatory drugs have been used as a treatment, however, the cellular and molecular mechanisms of the destructive processes in tendon are not clearly understood. It is thought that an inflammatory event may be involved as an initiating factor. Mediators of the inflammatory response include cytokines released from macrophages and monocytes. Interleukin-1 beta (IL-1 beta) is a candidate proinflammatory cytokine that is active in connective tissues such as bone and cartilage. We hypothesized that tendon cells would express receptors and respond to IL-1 beta in an initial "molecular inflammation" cascade, that is, connective tissue cell expression of cytokines that induce matrix destructive enzymes. This cascade results in expression of matrix metalloproteinases (MMPs) and aggrecanases that may lead to matrix destruction. Normal human tendon cells from six patients were isolated, grown to quiescence and treated with human recombinant IL-1 beta in serum-free medium for 16 h. Total RNA was isolated and mRNA expression assessed by semiquantitative RT-PCR. IL-1 beta (1 nM) induced mRNAs for cyclooxygenase 2 (COX2), MMP-1, -3, -13 and aggrecanase-1 as well as IL-1 beta and IL-6, whereas mRNAs for COX1 and MMP-2 were expressed constitutively. The IL-1 beta-treated tendon cells released prostaglandin E(2) (PGE(2)) in the medium, suggesting that the inducible COX2 catalyzed this synthesis. Induction of PGE(2) was detectable at 10 pM IL-1 beta. IL-1 beta also stimulated MMP-1 and -3 protein secretion. Induction of MMP-1 and -3 was detectable at 10 pM IL-1 beta. Post-injury or after some other inciting events, exogenous IL-1 beta released upon bleeding or as leakage of local capillaries may drive a proinflammatory response at the connective tissue cell level. The resulting induction of COX2, MMP-1 and -3 may underscore a potential for nonlymphocyte-mediated cytokine production of MMPs that causes matrix destruction and a loss of tendon biomechanical properties. Endogenous IL-1 beta might contribute to the process through a positive feedback loop by stimulating expression and accumulation of MMPs in the tendon matrix.

ADAM Proteins↗
PubMed2002

Postnatal mammary ductal growth: three-dimensional imaging of cell proliferation, effects of estrogen treatment, and expression of steroid receptors in prepubertal calves.

Cows may provide insights into mammary development that are not easily obtained using mouse models. Mammary growth in control and estrogen-treated calves was investigated to evaluate general patterns of proliferation and relationship to estrogen receptor (ER) expression. After in vivo labeling with bromodeoxyuridine (BrdU), serial histological sections of mammary tissue were used to generate three-dimensional reconstructions. BrdU-labeled cells were present throughout the highly branched terminal ducts. ER and progesterone receptors (PR) were colocalized in nuclei of ductal epithelial cells. However, basal cells and epithelial cells that were located in the central region of epithelial cords and those that lined the lumen of patent ducts were ER- and PR-negative, as were stromal cells. Cells along the basal portion of the epithelium were not myoepithelial. ER in mammary epithelial cells but not stromal cells is analogous to patterns in human breast but contrasts with localization in murine mammary gland. After estrogen stimulation, 99% of BrdU-labeled (and Ki67-labeled) epithelial cells were ER-negative. Data suggest that proliferation in response to estrogen treatment was initiated within ER-positive epithelial cells of the developing mammary gland and the signal was propagated in paracrine fashion to stromal elements and ER-negative epithelial cells.

Animals↗
PubMed2000

Ultrastructural and karyotypic examination of in vitro produced bovine embryos developed in the sheep uterus.

This study examined whether development of bovine in vitro produced (IVP) blastocysts in the sheep uterus resulted in morphologically and karyotypically normal elongation stage bovine blastocysts. Seven day IVP bovine blastocysts, resulting from either in vitro maturation and fertilization, nuclear transfer (NT), or parthenogenic activation, were surgically transferred at the blastocyst stage into sheep uteri. Sheep were sacrificed after 7-9 days, and blastocysts were flushed from their uteri. One of each kind of IVP bovine blastocyst was recovered from sheep uteri for analysis by transmission electron microscopy, and nine NT blastocysts were used to establish cell cultures that were analysed for chromosome complement. TEM analysis of in vivo-derived elongation stage bovine and ovine blastocysts was done for comparative purposes. Most ultrastructural features of the 13-19 day blastocysts were similar to earlier stage blastocysts except that distinct alternative mitochondrial morphologies were found between epiblast and trophectoderm cells. Monociliated cells, presumably nodal cells, were observed in the bovine epiblast and hypoblast, and retrovirus-like particles were elaborated by cells in these same areas. Development in the sheep uterus of IVP bovine blastocysts resulted in the presence of crystalloid bodies in the trophectoderm cells, and apoptotic and necrotic cells were observed in the epiblast tissue. Thus, in vivo incubation in the sheep uterus allowed nearly normal development to the elongated blastocyst stage and may be useful for assessment of NT bovine blastocyst developmental competence. Cell cultures derived from the NT blastocysts had normal chromosome complements suggesting that activation by ionomycin and 6-dimethyl-aminopurine did not cause detrimental changes in ploidy in those blastocysts that developed.

Animals↗
PubMed2000

Bovine blastocyst-derived trophectoderm and endoderm cell cultures: interferon tau and transferrin expression as respective in vitro markers.

Continuous cultures of bovine trophectoderm (CT-1 and CT-5) and bovine endoderm (CE-1 and CE-2) were initiated and maintained on STO feeder cells. CT-1 and CT-5 were derived from the culture of intact, 10- to 11-day in vitro-produced blastocysts. CE-1 and CE-2 were derived from the culture of immunodissected inner cell masses of 7- to 8-day in vitro-produced blastocysts. The cultures were routinely passaged by physical dissociation. Although morphologically distinct, the trophectoderm and endoderm both grew as cell sheets of polarized epithelium (dome formations) composed of approximately cuboidal cells. Both cell types, particularly the endoderm, grew on top of the feeder cells for the most part. Trophectoderm cultures grew faster, relative to endoderm, in large, rapidly extending colonies of initially flat cells with little or no visible lipid. The endoderm, in contrast, grew more slowly as tightly knit colonies with numerous lipid vacuoles in the cells at the colony centers. Ultrastructure analysis revealed that both cell types were connected by desmosomes and tight junctional areas, although these were more extensive in the trophectoderm. Endoderm was particularly rich in rough endoplasmic reticulum and Golgi apparatus indicative of cells engaged in high protein production and secretion. Interferon tau expression was specific to trophectoderm cultures, as demonstrated by reverse transcription-polymerase chain reaction, Western blot, and antiviral activity; and this property may act as a marker for this cell type. Serum protein production specific to endoderm cultures was demonstrated by Western blot; this attribute may be a useful marker for this cell type. This simple coculture method for the in vitro propagation of bovine trophectoderm and endoderm provides a system for assessing their biology in vitro.

Animals↗
PubMed1999

What is the optimal dose of intramuscular ketamine for pediatric sedation?

OBJECTIVE: The optimal dose of i.m. ketamine for ED procedural sedation in children is not known. The authors wished to quantify the dose-response of ketamine with respect to sedation adequacy, time to discharge, and adverse effects in order to identify an optimal dose. METHODS: The study was a consecutive case series of 1,022 children < or = 15 years of age given i.m. ketamine in the EDs of a university medical center and an affiliated county hospital over a nine-year period. Adequacy of sedation, time to discharge, and adverse effects were compared with dose administered. RESULTS: Doses in the sample averaged 3.96+/-0.69 mg/kg, with a range of 0.48 to 9.09 mg/kg. Children judged to be adequately sedated received higher doses compared with those inadequately sedated (3.94+/-0.44 mg/kg vs 3.77+/-0.49 mg/kg, p=0.041), and a nonsignificant trend was noted toward uniformly adequate sedation with increasing dose (< or =91% at <4.00 mg/kg, 93% at 4.00-4.49 mg/kg, and 100% at > or = 4.50 mg/kg). No significant difference or trend in time to discharge or adverse effects was noted between the children receiving <4.00 mg/kg and those receiving > or = 4.00 mg/kg of ketamine, and the study had power (alpha=0.05, beta=0.20) to detect a 9-minute difference in times to discharge, a 3.3% difference in rates of airway complications, a 5.6% difference in rates of emesis, and a 12.3% difference in rates of recovery agitation. CONCLUSION: Ketamine doses of 4 to 5 mg/kg i.m. produced adequate sedation in 93%-100% of children, suggesting that this dosing range may be optimal for ED procedural sedation. No difference in time to discharge or adverse effects was observed for lower or higher doses.

Anesthetics, Dissociative↗
PubMed1998

Intramuscular ketamine for pediatric sedation in the emergency department: safety profile in 1,022 cases.

STUDY OBJECTIVE: To determine the safety of intramuscular ketamine when administered by emergency physicians for pediatric procedures in accordance with a defined protocol. METHODS: We assembled a consecutive case series of children aged 15 years or younger who were given ketamine in the emergency departments of a university medical center and an affiliated county hospital over a 9-year period. A protocol for ketamine use (4 mg/kg, intramuscularly) was followed. Treating physicians were instructed to complete data forms recording complications and adequacy of sedation concurrent with patient care. Subsequent chart review was used to determine indications, adjunctive drugs, time to discharge, and adverse reactions for all patients. RESULTS: Intramuscular ketamine was administered 1,022 times, mainly for laceration repair and fracture reduction. Physicians completed data forms for 431 of treated children (42%). Transient airway complications occurred in 1.4%: airway malalignment (n = 7), laryngospasm (n = 4), apnea (n = 2), and respiratory depression (n = 1). All were quickly identified and treated without intubation or sequelae. Emesis occurred in 6.7%, without evidence of aspiration. Mild recovery agitation occurred in 17.6%, moderate to severe agitation in 1.6%. No child required hospitalization for complications caused by ketamine. Ketamine produced acceptable sedation in 98% of patients. The median time from injection to emergency department discharge was 110 minutes for children given a single dose of ketamine. CONCLUSION: Intramuscular ketamine may be administered safely by emergency physicians to facilitate pediatric procedures in accordance with a defined protocol and with appropriate monitoring. Ketamine is highly effective, has a wide margin of safety, does not require intravenous access, and uniquely preserves protective airway reflexes.

Adolescent↗
PubMed1998

Intravenous ketamine for pediatric sedation in the emergency department: safety profile with 156 cases.

OBJECTIVES: To determine the safety of i.v. ketamine when administered by emergency physicians (EPs) for pediatric procedures, and to contrast the sedation characteristics of the i.v. and i.m. routes. METHODS: The study was a retrospective consecutive case series of children aged < or =15 years given i.v. ketamine in the EDs of a university medical center and an affiliated county hospital over a 9-year period. A protocol for ketamine was used by treating physicians. Records were reviewed for adverse effects, indication, dosing, adjunctive drugs, inadequate sedation, and time to release. Results were contrasted with previously reported data for the i.m. route. RESULTS: During the study period i.v. ketamine was administered 156 times, primarily for laceration repair and fracture reduction. Transient apnea and respiratory depression occurred in one patient each; both were quickly identified and were without sequelae. Laryngospasm or aspiration was not noted in any children. There were 6 children with emesis and 2 with mild agitation during recovery. The median time from initial dose to ED release was 103 minutes (25th to 75th percentiles 76 to 146 minutes). The i.v. and i.m. routes were comparable in terms of adverse effects, inadequate sedation, and time to release. CONCLUSION: I.v. ketamine can be administered safely by EPs to facilitate pediatric procedures when used in a defined protocol. The sedation characteristics of the i.v. and i.m. routes appear comparable.

Adolescent↗
PubMed1997

The effect of intensity windowing on the detection of simulated masses embedded in dense portions of digitized mammograms in a laboratory setting.

The purpose of this study was to determine whether intensity windowing (IW) improves detection of simulated masses in dense mammograms. Simulated masses were embedded in dense mammograms digitized at 50 microns/pixel, 12 bits deep. Images were printed with no windowing applied and with nine window width and level combinations applied. A simulated mass was embedded in a realistic background of dense breast tissue, with the position of the mass (against the background) varied. The key variables involved in each trial included the position of the mass, the contrast levels and the IW setting applied to the image. Combining the 10 image processing conditions, 4 contrast levels, and 4 quadrant positions gave 160 combinations. The trials were constructed by pairing 160 combinations of key variables with 160 backgrounds. The entire experiment consisted of 800 trials. Twenty observers were asked to detect the quadrant of the image into which the mass was located. There was a statistically significant improvement in detection performance for masses when the window width was set at 1024 with a level of 3328. IW should be tested in the clinic to determine whether mass detection performance in real mammograms is improved.

Analysis of Variance↗
PubMed1997

Impact of a management assessment centre in developing proficient health managers.

There is growing use of management assessment centres within parts of New South Wales Health. The present study examined outcome benefits from managers who participated in the Australasian Management Competencies Assessment Centre, some 123 staff from one rural and one metropolitan area health service. Results confirmed greater use of personal development plans and increased attendance at continuing professional development among participants compared with like managers who had not participated. The paper argues strongly in favour of widespread use of management competencies assessment centres as a way to implement planned cultural change.

Adult↗
PubMed1996

Local anesthesia in outpatient knee arthroscopy: a comparison of efficacy and cost.

This study was performed to compare the efficacy, cost-effectiveness, and safety of general, regional, and local anesthesia when performing outpatient knee arthroscopy. The study consisted of two portions. A retrospective review of 256 outpatient knee arthroscopies was performed. The types of anesthesia used were general endotracheal, regional (epidural or spinal), and local. Comparisons were made between operative procedure, anesthesia procedure time, need for supplemental anesthesia, recovery room time and cost, pharmaceutical cost, and complications. A prospective study consisted of 100 consecutive outpatient knee arthroscopies performed using local anesthesia. Data identical to the retrospective portion were obtained. Visual analog scales were used in a patient questionnaire completed at the first postoperative visit to assess patient satisfaction with local anesthesia. The retrospective data showed similar demographics and operative procedures performed in the three study groups. The difference between operative time and total anesthetic time for the local group was 35 minutes less than for regional, and 23 minutes less than for the general group. These differences were statistically significant (P < or = .05). Total pharmaceutical cost was significantly less for the local group (P < or = .05). Recovery room cost for the local anesthesia group averaged $134 compared with $450 for regional and $527 for general. This difference was significant (P < or = .05). There were 19 complications with general anesthesia, 16 with regional anesthesia, and 2 with local. There were two regional and two local cases that needed subsequent general anesthesia. The prospective data showed nearly identical time and cost data. The patient questionnaire showed nearly universal acceptance and satisfaction with the use of local anesthesia. The use of local anesthesia for outpatient knee arthroscopy is safe, effective, and well accepted. The use of local anesthesia was shown to save a minimum of $400 per case compared with the other anesthetic methods studied.

Adult↗
PubMed1995

Educational and long-term therapeutic intervention in the ED: effect on outcomes in adult indigent minority asthmatics.

Minorities have increased morbidity and mortality rates resulting from asthma. The segment of minorities that is socioeconomically depressed often uses the emergency department (ED) as their primary site of medical care. For these reasons, we provided major long-term therapeutic intervention as well as intensive education in the ED for indigent adult African American asthmatics. We intervened in the cases of 30 patients who were frequent visitors to the ED over the previous 2 years. The intervention consisted of 1 hour of education in the ED before discharge regarding the prevention of asthma, the importance of decreasing inflammation as a means of improving asthma control, self-monitoring with a peak flow meter, and a demonstration of correct inhalation technique with metered-dose inhalers and a spacer device. Further, the intervention included management consistent with recent NIH Guidelines, stressing inhaled corticosteroids. After the intervention in the ED, patients were scheduled for follow-up asthma clinic visits. Outcome measures were ED visits and hospitalizations for 1 year after the ED intervention. Using the same inclusion/exclusion criteria, a retrospective control group of 22 patients for the same time period was compared with the intervention group. Before our intervention, the mean number of ED visits per patient for the previous 2 years was 4.4 +/- 2.7, and after the intervention, 2.6 +/- 2.6 (P < .01). The control group did not show a difference in the number of ED visits (3.4 +/- 2.6 before and 3.5 +/- 2.7 after, P = .96). After the intervention, the mean number of hospitalizations decreased significantly in the study group (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Aromatase inhibitors. Synthesis and biological activity of androstenedione derivatives.

The synthesis and biological evaluation of androstenedione derivatives as inhibitors of estrogen biosynthesis are described. The results show that 4-hydroxy analogues are among the most potent in vitro inhibitors of the series. Esterification of the 4-hydroxy steroids generally reduced activity. Further conjugation of the 3-keto 4-ene system to give 4-hydroxy-4,6-androstadiene-3,17-dione caused more rapid inactivation of aromatase in rat ovarian microsomes than 4-hydroxyandrostenedione. Some compounds exhibited differences in activity when tested for inhibition of human placental microsomes vs. rat ovarian microsomes. The 4-hydroxyandrostenedione derivatives and their nonbulky esters were generally more potent in vitro and in vivo inhibitors than other substituted steroids in the series. Several of the synthesized compounds markedly reduce (50-81%) estrogen levels in rats on proestrus and/or had antifertility action. To date, none of the compounds surpassed the in vivo inhibitory action of 4-hydroxy-4-androstene-3,17-dione or its 4-acetate derivative.

Androstenedione↗
PubMed1976

Placental aging monitored by gray scale echography.

With gray scale ultrasonics echography, it is possible to identify changes in placental anatomy which formerly have been recognized only by examination of the placenta after delivery. By serial examinations these changes can be detected as they occur. The significance of the changes is discussed and an association between the premature appearance of aging of the placenta and a decline in placental function is noted.

Female↗