Baker V. Arbor Drugs, Inc.: pharmacists beware of voluntarily assuming the duty to protect against harmful drug interactions.
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Drug Interactions↗
Biomedical subjects
M F Smith
Publications and source records attributed to M F Smith.
Percutaneous multielectrode endocardial mapping during ventricular tachycardia in the swine model.
BACKGROUND: Identification of critical areas within the ventricular tachycardia circuit is a prerequisite for catheter ablation. Currently, mapping during ventricular tachycardia, usually performed with standard catheters, is difficult and time-consuming and can be used only in patients with hemodynamically stable tachycardia. METHODS AND RESULTS: A total of 43 pigs underwent closed-chest induction of myocardial infarction. A basket-shaped catheter carrying 64 electrodes was deployed in the left ventricle during normal sinus rhythm. Unipolar pacing at 3 mA was successful in 78% of the basket catheter electrodes, demonstrating good electrode-tissue contact. Hemodynamic and echocardiographic measurements did not reveal any significant interference with myocardial or valvular function during or after catheter deployment. One hundred eighteen episodes of monomorphic ventricular tachycardia were induced in 28 pigs through right ventricular stimulation, 81 of which were mapped and analyzed. Ventricular tachycardia mapping was rapid, requiring only several beats and < 10 seconds to complete. Presystolic potentials, a possible target for ablation, were identified in 58% of the tachycardia episodes mapped. Pathological examination revealed only minor valvular and endocardial catheter-induced lesions immediately after mapping and none a month later. CONCLUSIONS: The multielectrode catheter enables rapid and safe percutaneous endocardial mapping of ventricular tachycardia in the swine model. Exploration of the clinical potential of the multielectrode catheter seems warranted.
Animals↗
IL-4-induced expression of the IL-1 receptor antagonist gene is mediated by STAT6.
IL-4 alone or in cooperation with LPS can induce the expression of the gene encoding the secreted-type IL-1 receptor antagonist (sIL-1ra) in mononuclear phagocytes. To determine the nuclear signaling mechanisms involved in this response, the region flanking the transcription start site of the human sIL-1ra gene was placed upstream of the luciferase reporter gene, and the function of specific sequence elements was analyzed following transient transfection in the macrophage-like cell line RAW264.7. A region located between -250 and -200 bases relative to the transcription start site was necessary for response to IL-4 alone and for cooperation between IL-4 and LPS. This 50-bp region contains two inverted repeat elements that represent potential binding sites for members of the signal transducer and activator of transcription (STAT) gene family (STAT-binding elements (SBEs)). Site-directed mutagenesis of the distal SBE abolished IL-4 responsiveness, and multiple copies of this motif were able to confer IL-4 sensitivity to luciferase expression in the context of a heterologous (herpes virus thymidine kinase) promoter. Mutation of the proximal SBE in the intact IL-1ra promoter had little or no effect on response to IL-4, and this sequence motif was inactive when examined alone. Electrophoretic mobility shift assays using an oligonucleotide corresponding to the distal SBE identified a single binding activity that was detected in nuclei within 15 min of IL-4 treatment and that was recognized by Ab to STAT6. These results indicate that IL-4-induced STAT6 is required for IL-4-induced transcriptional activation of the sIL-1ra gene.
Animals↗
Debate over NHS-wide network is centered on wrong issue.
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Computer Communication Networks↗
Data protection, health care, and the new European directive.
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Computer Security↗
Ontogenies of messenger RNA encoding tissue inhibitor of metalloproteinases 1 and 2 within bovine periovulatory follicles and luteal tissue.
Tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) are important regulators of extracellular matrix remodeling and also possess growth factor activity. The objective of these studies was to characterize TIMP-1 and TIMP-2 mRNA expression by bovine periovulatory follicles/ corpora hemorrhagica (Experiment 1) and luteal tissue (Experiment 2). In Experiment 1, beef heifers (n = 27) were ovariectomized at-16 (n = 6), 0 (n = 5), 8 (n = 3), 16 (n = 4), 24 (n = 4), or 48 (n = 5) hr relative to a gonadotropin-releasing hormone induced gonadotropin surge (40 hr after prostaglandin F2 alpha-induced luteolysis). Total cellular RNA was isolated from the large steroidogenically active follicle or corpus hemorrhagicum obtained from each animal, and the expression of TIMP-1 and TIMP-2 mRNA was subsequently examined by northern and dot blot analysis. The expression of TIMP-1 or TIMP-2 mRNa did not differ in preovulatory follicles collected at -16 vs. 0 hr. Concentrations of both TIMP-1 and TIMP-2 mRNA (picograms per microgram of tissue DNA) were increased (P < 0.05) at 8 hr postgonadotropin surge, had declined to presurge levels by 24 hr (P < 0.05), and were increased (P < 0.05) in corpora hemorrhagica collected at 48 hr after a gonadotropin surge. In Experiment 2, corpora lutea were collected from beef heifers on Days 4, 10, 15 (n = 4 each), or 19 (n = 3) postestrus (Day 0 = estrus). Concentrations of TIMP-1 mRNA (picograms per microgram of tissue DNA) were greater in corpora lutea collected on Day 4 (P < 0.05) vs. Day 10, 15, or 19. Concentrations of TIMP-2 mRNA increased (P < 0.05) from Day 4 to 15 and decreased (P < 0.05) by Day 19. We conclude that: 1) during the periovulatory period, the ontogenies of TIMP-1 and TIMP-2 mRNA expression are similar, whereas 2) during luteal phase, TIMP-1 mRNA expression is maximal during the early luteal phase, whereas concentrations of TIMP-2 mRNA peak during the midluteal phase. TIMP-1 and TIMP-2 may play important roles in the regulation of extracellular matrix remodeling during the periovulatory period and the subsequent luteal phase.
Animals↗
Ontogeny and regulation of luteinizing hormone receptor messenger ribonucleic acid within the ovine corpus luteum.
Although LH regulates corpus luteum (CL) function and LH receptor (LHR) binding has been characterized within ovine CL, changes in LHR mRNA expression have not been documented. The objectives here have been to assess relative amounts of LHR mRNA in ovine CL throughout the estrous cycle and during luteolysis by ribonuclease protection analysis. In experiment 1, LHR mRNA was quantified within CL collected on Days 3, 7, 10, 13, and 16 post-estrus (n = 3, 4, 4, 3, and 4, respectively). LHR mRNA differed throughout the luteal phase (p < 0.01), with higher concentrations found during the midluteal phase (Days 10 and 13) than during the early (Day 3) or late (Day 16) luteal phase (p < or = 0.05). In experiment 2, LHR mRNA content was determined within pools of Day 10 small (n = 4) or large (n = 4) luteal cells. Relative amounts of LHR mRNA were not different (p = 0.1) in small (2.23 +/- 0.22 relative units) vs. large (1.62 +/- 0.22 relative units) luteal cells. In experiment 3, CL were collected at 0, 6, 12, or 24 h after injection of 15 mg prostaglandin F2 alpha) on Day 10 post-estrus (n = 4, 4, 3, and 4, respectively). LHR mRNA content fell during PGF2 alpha-induced luteolysis (p < 0.002), decreasing significantly by 6 h (1.76 vs. 1.10 relative units; p < or = 0.05). By 24 h, levels were approximately 60% of those detected within 0-h controls (1.76 vs. 0.79 relative units; p < 0.05). These results indicate that changes in LHR mRNA during the luteal phase correlates well with previously reported changes in LHR binding. After PGF2 alpha administration, LHR mRNA falls earlier than the reported drop in LHR binding sites occurs.
Animals↗
Immunolocalization of tissue inhibitor of metalloproteinases-1 within ovine periovulatory follicular and luteal tissues.
In previous studies, tissue inhibitor of metalloproteinases (TIMP)-1 mRNA increased in follicular tissue after the preovulatory gonadotropin surge and was expressed in luteal tissue. However, the localization of TIMP-1 protein within ovine periovulatory follicular and luteal tissues is unknown. The objectives of the present study were to 1) localize TIMP-1 within follicles collected before and after a preovulatory gonadotropin surge and within Day 3 and Day 10 corpora lutea (CL), 2) determine whether TIMP-1 was colocalized to Day 10 luteal cells with oxytocin or TIMP-2, and 3) determine whether TIMP-1 was present within secretory granules of large luteal cells. Ovaries were removed from ewes before (presurge; n = 4) or 12-14 h after (postsurge; n = 5) an LHRH-induced gonadotropin surge (36 h following PGF2 alpha-induced luteolysis; objective 1). Additionally, ovaries containing CL were collected on Days 3 (n = 5; objective 1) and 10 (n = 4, 3, and 2 for objectives 1, 2, and 3, respectively). TIMP-1 immunoreactivity was observed within the granulosa cells of postsurge but not presurge follicles. On Days 3 and 10, TIMP-1 was localized within luteal tissue in a cell-specific manner. On Day 10, many of the cells that were immunopositive for TIMP-1 were judged to be large luteal cells on the basis of morphology (diameter > 22 microns; round nucleus) and colocalization with oxytocin and TIMP-2. Electron microscopy demonstrated that TIMP-1 was localized to secretory granules undergoing exocytosis from Day 10 large luteal cells. These data indicate that TIMP-1 is produced by granulosa cells following a gonadotropin surge and is packaged in secretory granules by large steroidogenic cells of the ovine CL.
Animals↗
Characterization of ovine stem cell factor messenger ribonucleic acid and protein in the corpus luteum throughout the luteal phase.
Stem cell factor (SCF) is a growth factor known to have profound effects on the proliferation, migration, differentiation, and survival of numerous cell types, including those of the ovary. The objectives of the present study were to identify and characterize expression of this growth factor in the ovine corpus luteum (CL). A 952-bp cDNA was amplified from Day 3 (Day 0 = estrus) ovine luteal total cellular (tc) RNA by reverse transcriptase-polymerase chain reaction and determined to encode SCF. Northern analysis of Day 10 luteal poly(A)+ RNA indicated one major transcript of approximately 6.5 kb. SCF mRNA was localized within Day 3 and Day 10 CL by in situ hybridization and was expressed throughout luteal tissue on both days examined. To asses expression throughout the luteal phase, SCF mRNA was quantified by ribonuclease protection assay in tcRNA collected on Day 3, 7, 10, 13, and 16; values did not differ across days (p > 0.10). Similarly, SCF mRNA was quantified in tcRNA isolated from pools of Day 10 large and small steroidogenic cells (n = 4 and 3, respectively); levels did not differ (p > 0.10) between cell types. In addition, SCF protein was detected in CL on Days 3 and 10, and was expressed in a cell-specific manner in cells with morphological characteristics of large and small luteal cells. These data indicate that SCF may be involved in communication among steroidogenic cells and/or between steroidogenic and nonsteroidogenic cells of the CL.
Amino Acid Sequence↗
Messenger ribonucleic acid for insulin-like growth factors-I and -II, insulin-like growth factor-binding protein-2, gonadotropin receptors, and steroidogenic enzymes in porcine follicles.
Several aspects of growth, development, and steroidogenesis in ovarian follicles are controlled by the interaction of insulin-like growth factors (IGF-I and IGF-II) and gonadotropins (LH and FSH). The objective of this study was to determine the developmental stage and location at which mRNA for IGF, IGF-binding protein (IGFBP)-2, gonadotropin receptors, and steroidogenic enzyme genes are expressed within porcine follicles. Ovaries from pigs on Days 10 (n = 3; midluteal phase) and 19 (n = 3; preovulatory phase) of the estrous cycle were collected, frozen, and sectioned. The mRNA for IGF-I, IGF-II, IGFBP-2, LH receptor, FSH receptor, cytochrome P450 side-chain cleavage (P450scc), 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 17 alpha-hydroxylase (P45017 alpha), and aromatase (P450arom) were detected by in situ hybridization, and relative amounts were determined by image analysis. Expression of mRNA for IGF-I and IGF-II was cell specific (granulosa and theca interna cells, respectively) and increased with follicular size. The IGFBP-2 mRNA was expressed in greater amounts for theca interna cells than for granulosa cells. The pattern of expression for LH and FSH receptors diverged as follicles grew. For LH receptor, mRNA was detected in the theca interna cells of small antral follicles and in both the theca interna and granulosa cells of large antral follicles. Amount of LH receptor mRNA increased with follicular diameter. For FSH receptor, mRNA increased as follicles grew to a small antral size. However, FSH receptor mRNA disappeared in large antral follicles on Day 19 of the estrous cycle. Steroidogenic enzyme mRNA for 3 beta-HSD (theca interna cells), P450scc (theca interna cells), P45017 alpha (theca interna cells), and P450arom (granulosa cells) increased with follicular diameter. In summary, coordinated expression of IGF, IGFBP-2, gonadotropin receptors, and steroidogenic enzyme mRNA throughout different stages of follicular development was observed. Changes in mRNA suggested increased IGF-I and -II action and a switch from FSH to LH dependence in porcine preovulatory follicles.
3-Hydroxysteroid Dehydrogenases↗
Dose responses for neostigmine and edrophonium as antagonists of mivacurium in adults and children.
BACKGROUND: Reversal of neuromuscular blockade induced with pancuronium, d-tubocurarine, or doxacurium is achieved using smaller doses of neostigmine in adults than in children. Also, pancuronium- and doxacurium-induced blockade is reversed with smaller doses of edrophonium in children than in adults. The purpose of this study was to compare the spontaneous and neostigmine- and edrophonium-assisted recovery of mivacurium-induced neuromuscular block in adults and children. METHODS: Fifty-four adults, aged 40.1 +/- 10.9 yr, and 54 children, aged 4.9 +/- 0.7 yr, physical status ASA 1-2, were studied during propofol/fentanyl/nitrous oxide anesthesia. A Datex relaxograph was used to monitor the electromyographic response of the adductor pollicis to train-of-four stimulation of the ulnar nerve every 10 s. After induction of anesthesia, 0.2 mg x kg(-1) intravenous mivacurium was administered followed by an infusion to maintain 90-95% T1 block. At the end of surgery, one of four doses of neostigmine (5, 10, 20, and 50 micrograms x kg(-1)) or edrophonium (100, 200, 400, and 1,000 micrograms x kg(-1)) or placebo was given, by random allocation, when T1 had recovered to 10%. Values of T1 and train-of-four were measured for 10 min. RESULTS: Spontaneous recovery proceeded more rapidly in children than in adults. At 10 min, T1 had recovered to 97 +/- 2% (SD) in children compared with 69 +/- 11% in adults and train-of-four to 84 +/- 5% versus 30 +/- 13% (P<0.0001). In children, 10 min after reversal, recovery of T1 and train-of-four was not different from control after edrophonium and was enhanced only by the larger doses of neostigmine. In adults, recovery was accelerated by both edrophonium and neostigmine. Five minutes after reversal, recovery was improved by either drug in adults and in children. CONCLUSIONS: Spontaneous recovery from mivacurium- induced neuromuscular block is more rapid in children than in adults. Ten minutes after attempted reversal, recovery is accelerated by edrophonium and usually by neostigmine in adults but not in children. Thus, when reversal is required, edrophonium may be preferred to neostigmine.
Adult↗
Residual block after mivacurium with or without edrophonium reversal in adults and children.
BACKGROUND: The rapid recovery from mivacurium- induced neuromuscular block has encouraged omission of its reversal. The purpose of this study was to determine, in children and in adults, whether failure to reverse mivacurium neuromuscular block was associated with residual neuromuscular block on arrival in the postanesthesia care unit. METHODS: In 50 children, aged 2-12 yr, and 50 adults, aged 20-60 yr, anesthesia was induced and maintained with propofol and fentanyl, and neuromuscular block was achieved by an infusion of mivacurium, to maintain one or two visible responses to train-of-four (TOF) stimulation of the ulnar nerve. At the end of surgery, mivacurium infusion was stopped, and 10 min later, reversal was attempted with saline or 0.5 mg x kg(-1) edrophonium by random allocation. On arrival in the postanesthesia care unit, a blinded observer assessed patients clinically and by stimulation of the ulnar nerve with a Datex electromyogram in the uncalibrated TOF mode. RESULTS: Children arrived in the postanesthesia care unit 8.2 +/- 3-4 min after reversal of neuromuscular block and showed no sign of weakness, either clinically or by TOF stimulation. Although TOF ratio was greater in children who had received edrophonium (1.00 +/- 0.05 vs. 0.93 +/- 0.01, P<0.01), TOF was >0.7 in all children. Adults arrived in the postanesthesia care unit 12.9 +/- 5.3 min after reversal of neuromuscular block(P<0.01 vs. children). Six in the saline group demonstrated weakness (two required immediate reversal of neuromuscular block, and TOF was <0.7 in four others), compared with TOF <0.7 in only one of the edrophonium group (P<0.05). CONCLUSIONS: This study demonstrated that, in adults, failure to reverse mivacurium neuromuscular block was associated with an increased incidence of residual block. Such weakness was not observed in children receiving similar anesthetic and neuromuscular blocking regimens.
Adult↗
Differential gene expression within the ovine corpus luteum: identification of secreted protein acidic and rich in cysteine as a major secretory product of small but not large luteal cells.
Limited information is available regarding secretory proteins of the corpus luteum (CL), and the potential local role these proteins may play in control of luteal function. An ovine small luteal cell complementary DNA library was immunologically screened with a polyclonal antiserum generated against small cell secretory proteins. A relatively abundant complementary DNA (approximately 2.1 kb) encoding a calcium binding glycoprotein Secreted Protein Acidic and Rich in Cysteine (SPARC) was isolated. Production of SPARC protein by ovine luteal cells was confirmed by immunoprecipitating it from labeled culture medium. Expression of SPARC messenger RNA (mRNA) was examined within CL collected on days 3, 7, 10, 13, and 16 post estrus (n = 4, 4, 4, 3, and 4 respectively), and within pools of purified small (n = 3) and large (n = 4) luteal cells by Northern and dot blot analysis. Amounts of SPARC mRNA increased during the early luteal phase, peaked by day 7 (P < 0.05) and subsequently declined on days 10 and 13 (P < 0.05). SPARC mRNA content was significantly higher in the small than in the large cells (P < 0.003). In situ hybridization showed that SPARC mRNA was localized to the thecal layer of Graafian follicles and to day 3 and day 10 CL. Within CL, immunohistochemistry indicated that SPARC protein was associated with small luteal cells (spindle shaped, avg = 17 microM in diameter) but not with large cells. This specific localization to small cells was confirmed by colocalization of SPARC with 3 beta-hydroxysteroid dehydrogenase. We conclude that SPARC is a major secretory product of small steroidogenic luteal cells of the ovine CL. As SPARC is known to modulate many aspects of tissue reorganization, expression by small luteal cells may play a role in regulation of CL maturation.
3-Hydroxysteroid Dehydrogenases↗
Telemedicine and safety.
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Computer Communication Networks↗
Use of oversized bandage soft contact lenses in the management of early hypotony following filtration surgery.
BACKGROUND AND OBJECTIVE: Initial overdrainage following filtration surgery can be frustrating to manage. The authors reviewed the records of 10 patients with early postoperative hypotony following filtration surgery who were treated with application of an oversized 17.0-mm bandage soft contact lens (BSCL). PATIENTS AND METHODS: Nine eyes had undergone trabeculectomy with either mitomycin-C or 5-fluorouracil intraoperative application, and one eye had undergone tenonectomy 4 years following trabeculectomy. On postoperative day 1, seven eyes were hypotonous, and three other eyes became hypotonous following suture removal or lysis. An oversized 17.0-mm BSCL was placed immediately following the diagnosis of hypotony on all eyes except one, which had the BSCL applied after 24 hours of observation. RESULTS: In 9 of 10 cases intraocular pressure rose 5 to 12 mm Hg following placement of the BSCL. During a 6- to 18-months follow-up, all successfully treated eyes had final intraocular pressures of 5 to 11 mm Hg, with extensive low to moderate height blebs. CONCLUSION: Oversized BSCLs can be a useful tool in the management of early hypotony following filtration surgery.
Aged↗
Injection of autologous blood for bleb leaks in New Zealand white rabbits.
PURPOSE: Bleb leaks after trabeculectomy with antimetabolites can be recalcitrant to therapy. Peribleb autologous blood injections are a moderately successful new treatment modality for such leaks. However, it is unclear what mechanism the injections work to achieve leak resolution. METHODS: A randomized, prospective study in the rabbit model was undertaken to evaluate further the clinical and histologic effects of peribleb autologous blood injection after leak induction in mitomycin-C exposed blebs, compared to controls that received only peribleb balanced salt solution injections. RESULTS: In the blood-treated eyes, all bleb leaks healed. Control eyes either demonstrated persistent bleb leaks with shallow anterior chambers or failed blebs that were Seidel negative. Histologic results were remarkable for increased peribleb cellularity and collagen deposition in the blood-treated eyes, compared to controls. CONCLUSIONS: Peribleb autologous blood injections are associated with bleb leak resolution, increased peribleb cellularity, and collagen deposition in the rabbit model.
Animals↗
Comparison of the Baerveldt glaucoma implant with the double-plate Molteno drainage implant.
OBJECTIVE: To compare the 350-mm2 Baerveldt implant with the double-plate Molteno implant in the treatment of eyes with complicated glaucoma. DESIGN: Retrospective chart review of a consecutive series of drainage implants. SETTING: University-based referral practice. PATIENTS: Thirty-four consecutive patients (37 eyes) undergoing glaucoma drainage device implantation because of uncontrolled, complicated glaucoma. INTERVENTION: Eighteen eyes underwent 350-mm2 Baerveldt implantation and 19 eyes underwent double-plate Molteno implantation. MAIN OUTCOME MEASURES: Intraocular pressure (IOP) control, visual acuity outcome, and complication rate. RESULTS: Mean preoperative IOP was 30.2 mm Hg in the Baerveldt group, with an average of 2.7 antiglaucoma medications, and 28.4 mm Hg in the Molteno group, with an average of 2.4 antiglaucoma medications. With an average follow-up of 11.3 months (range, 5 to 16 months), mean IOP at the final visit was 13.1 mm Hg (range, 7 to 21 mm Hg) in the Baerveldt group, with an average of 1.3 medications, and 13.4 mm Hg (range, 8 to 25 mm Hg) in the Molteno group, with an average of 0.8 medications. Final IOP was between 7 and 19 mm Hg in 16 of 18 Baerveldt eyes and in 17 of 19 Molteno eyes. Visual acuity (when it could be checked) remained stable (+/- 2 Snellen lines) in 17 of 17 eyes in the Baerveldt group and in 17 of 19 eyes in the Molteno group. Complications in the Baerveldt group included two cases (11%) of flat anterior chamber after stent removal, one case (6%) of intermittently symptomatic diplopia, and one case (6%) of endophthalmitis. In the Molteno group there were two graft failures (11%) and one eye (5%) with loss of central field. CONCLUSIONS: Both types of drainage implants provide excellent postoperative IOP control. Early stent removal should be avoided if possible in eyes with Baerveldt implants.
Anterior Chamber↗
Intercellular adhesion molecule-1 promotes neutrophil-mediated cytotoxicity.
BACKGROUND: Interaction of the CD11/CD18 complex on polymorphonuclear neutrophils (PMNs) and intercellular adhesion molecule (ICAM)-1 on endothelium is a critical event in PMN-mediated tissue injury. In addition, increased expression of ICAM-1 on type I pneumocytes has been identified in a variety of pulmonary disorders associated with PMN-induced inflammation. We hypothesized that ICAM-1 up-regulation is sufficient to promote cytotoxicity via activated PMNs. METHODS: The complementary DNA for human ICAM-1 was transfected into Chinese hamster ovarian (CHO) cells, which do not inherently express this adhesion receptor, by using the expression vector CD1.8. Fluorescence-activated cell sorter analysis revealed 62% CHO cell surface expression of ICAM-1. Wild type and transfected CHO cells were labeled with chromium 51 and exposed to quiescent or activated (1 mumol/L phorbol myristate acetate) PMNs for 4 hours. Subsets were pretreated with a monoclonal antibody to ICAM-1. PMN cytotoxicity was determined by specific percent 51Cr release. RESULTS: Incubation of quiescent PMNs with wild type and transfected CHO cells produced nominal cell lysis, 0.5% +/- 0.3% and 0.2% +/- 0.2%, respectively. Activated PMNs produced 13.6% +/- 3.2% versus 1.4% +/- 0.7% cell lysis, comparing transfected with wild type CHO cells, and 0.5% +/- 0.2% cell lysis after pretreatment with a monoclonal antibody to ICAM-1, p < 0.01. CONCLUSIONS: ICAM-1 up-regulation is sufficient to promote cytotoxicity via activated PMNs. This may represent a potential target for attenuating PMN-mediated injury to endothelial and other cell lines, including parenchyma.
Animals↗