A 16-year-old with abdominal pain.
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Abdominal Pain↗
Biomedical subjects
M F Smith
Publications and source records attributed to M F Smith.
Gonadotropin induction of ovulation and corpus luteum formation in young estrogen receptor-alpha knockout mice.
Estrogen receptor-alpha (ERalpha) knockout (ERalphaKO) female mice are infertile. Initially, they exhibit normal follicular development, but by 4-5 wk of age, they begin to develop hemorrhagic ovarian cysts. Follicles in adult ERalphaKO female mice progress to the graafian stage, but there are no corpora lutea (CL). To test whether ERalpha is required for ovarian folliculogenesis, ovulation, and CL formation, eCG and hCG were used to ovulate 3- to 5-wk-old ERalphaKO and wild-type (WT) sibling mice. Gonadotropin administration resulted in ovulation in both ERalphaKO and WT mice. Gonadotropin-treated ERalphaKO females that ovulated produced 7.09 +/- 0.77 oocytes per mouse, whereas gonadotropin-treated WT female mice had 16.17 +/- 0.84 oocytes. Surprisingly, ruptured ERalphaKO ovarian follicles developed into CL that had normal morphology. Gonadotropin-treated ERalphaKO mice had 3-fold higher concentrations of serum progesterone than did control ERalphaKO mice that had been administered saline rather than gonadotropins. Thus, the CL in gonadotropin-treated ERalphaKO mice appeared to be steroidogenically functional. On the basis of these findings, ovarian folliculogenesis, ovulation, and CL formation can occur in the absence of ERalpha, although to a lesser extent than in WT mice.
Animals↗
The prolonged duration of rocuronium in Chinese patients.
We compared the potency and duration of action of rocuronium in Chinese and Caucasian patients during general anesthesia. Thirty-six women (18 Caucasian and 18 Chinese) and 36 children (18 Caucasian and 18 Chinese) were evaluated during the administration of propofol/fentanyl anesthesia. Patients in each age group were randomized into three subgroups to receive single doses of 0.06, 0. 12, or 0.18 mg/kg rocuronium (adults) or 0.12, 0.18, or 0.24 mg/kg rocuronium (children). Neuromuscular blockade was assessed by electromyography of the adductor pollicis after train-of-four (TOF) stimulation of the ulnar nerve. Dose response curves were constructed when maximum neuromuscular depression of the first twitch of the train (T(1)) was obtained. A second bolus dose of rocuronium was then administered to a total dose of 0.6 mg/kg. The times of spontaneous recovery to T(1) 10%, 25%, and 90% of control and to TOF 0.25, 0.50, and 0.70 were recorded. For both adults and children, recovery occurred later in Chinese than in Caucasian patients (P<0.05 for T(1) of 10%, 25%, 75%, and 90% and TOF to 0.7). The 50% effective dose was smaller in Chinese adults (125+/-63 vs. 159+/-66 microg/kg) and Chinese children (171+/-43 vs. 191+/-46 microg/kg) than in Caucasian adults and children, but the difference was not statistically significant. In adults, time to 25% T(1) recovery was 43+/-13 min in Chinese patients and 33+/-10 min in Caucasian patients (P<0.05). The corresponding values were more rapid for children: 30+/-10 and 24+/-6 min (P<0.05). We conclude that the recovery from rocuronium neuromuscular blockade was longer in Chinese compared with Caucasian patients and in adults compared with children.
Adolescent↗
Development of an estrus synchronization protocol for beef cattle with short-term feeding of melengestrol acetate: 7-11 synch.
An estrus synchronization protocol (7-11 Synch) was developed to synchronize the first follicular wave and timing of ovulation in postpartum beef cows. In Exp. 1, follicular development and timing of ovulation in response to the following protocol were evaluated. Beef heifers (n = 12) and cows (n = 6), at random stages of the estrous cycle, were fed melengestrol acetate (MGA; .5 mg x animal(-1) x d(-1)) for 7 d and injected with PGF2alpha (PG; 25 mg) on the last day of MGA. A second injection of PG was administered 11 d after cessation of MGA. After the second injection of PG, estrus was synchronized in 6/12 heifers and 3/6 cows. The interval to estrus in heifers and cows was 54 and 64 h, respectively (P > .10). All animals exhibiting estrus ovulated first-wave follicles. Animals that failed to respond to the second injection of PG were in estrus later than 6 d after cessation of MGA and had corpora lutea that were unresponsive to the injection of PG. Based on the variation in interval to estrus following the first PG injection on the last day of MGA feeding in Exp. 1, an injection of GnRH (100 microg) was added to the protocol 4 d after the cessation of MGA to ensure ovulation or luteinization of dominant follicles and synchronization of first-wave follicular development. This revised protocol was termed "7-11 Synch." In Exp. 2, two estrus synchronization protocols were compared. Multiparous beef cows were stratified by breed and postpartum interval and randomly assigned to the 7-11 Synch (n = 44) or Select Synch protocols (GnRH injection followed by PG injection 7 d later; n = 45). Timing of estrus after the last PG injection (0 h) ranged from 42 to 102 h in the 7-11 Synch group and -30 to 114 h in the Select Synch group. Eight cows (18%) in the Select Synch group exhibited estrus 30 h before to 18 h after PG. Synchronized estrus peaked between 42 and 66 h after the last PG injection, and a maximum number of cows were in estrus at 54 h for both treatment groups. Synchrony of estrus from 42 to 66 h was greater (P < .05) in 7-11 Synch (91%: 41/44) than in Select Synch cows (69%: 31/45). Artificial insemination pregnancy rate from 42 to 66 h was greater (P < .05) in the 7-11 Synch group (66%: 29/44) than in the Select Synch group (40%: 18/45). In summary, the 7-11 Synch protocol improved synchrony of estrus without reducing fertility. This protocol has potential future application for fixed-time AI in beef cattle production systems.
Animals↗
Enhanced short-term plasmid transfection of filtration surgery tissues.
PURPOSE: To quantify and localize plasmid transfection of filtration surgery tissues using two delivery techniques. METHODS: Full-thickness filtering procedures were performed on eyes of New Zealand albino rabbits. In 10 eyes, naked plasmid DNA in saline was either injected beneath Tenon's capsule at the filtration site or absorbed into a collagen shield that was then placed external to the sclerostomy and under the Tenon's capsule. Forty-eight hours after surgery, levels of the reporter gene, chloramphenicol acetyltransferase (CAT) were measured in samples of ocular tissues. In two additional eyes, the ss-galactosidase (ss-GAL:) reporter gene expression was localized histologically. RESULTS: Injection of plasmid DNA in saline vehicle into the filtration bleb produced readily detectable CAT activity in bleb tissue (conjunctiva, Tenon's capsule, and sclera) whereas CAT activity was nearly undetectable in samples of the cornea, iris-ciliary body, and tissues located opposite the bleb site. Delivery of the plasmid DNA into the bleb through a collagen shield increased CAT activity 30-fold over injection of plasmid in saline (2711 +/- 567 mU/mg versus 92 +/- 38 mU/mg). ss-Gal activity was imaged only in the region of the bleb, and microscopic examination showed ss-Gal activity localized to Tenon's capsule fibroblasts, with minimal ss-Gal activity observed in inflammatory cells or scleral fibroblasts. CONCLUSIONS: Transfection of filtration tissues is enhanced by absorption of naked DNA into a collagen shield. Furthermore, transfection is localized to the fibroblasts and inflammatory cells of the filtration bleb site. Gene therapy using naked plasmid DNA and a simple collagen shield delivery vehicle may be useful for regulating wound healing after glaucoma surgery.
Animals↗
Roles of intracellular calcium and NF-kappa B in the Clostridium difficile toxin A-induced up-regulation and secretion of IL-8 from human monocytes.
Clostridium difficile causes an intense inflammatory colitis through the actions of two large exotoxins, toxin A and toxin B. IL-8 is believed to play an important role in the pathophysiology of C. difficile-mediated colitis, although the mechanism whereby the toxins up-regulate the release of IL-8 from target cells is not well understood. In this study, we investigated the mechanisms through which toxin A induces IL-8 secretion in human monocytes. We found that cellular uptake of toxin A is required for the up-regulation of IL-8, an effect that is not duplicated by a recombinant toxin fragment comprising the cell-binding domain alone. Toxin A induced IL-8 expression at the level of gene transcription and this effect occurred through a mechanism requiring intracellular calcium and calmodulin activation. Additionally, the effects of toxin A were inhibited by the protein tyrosine kinase inhibitor genistein, but were unaffected by inhibitors of protein kinase C and phosphatidylinositol-3 kinase. We determined that toxin A activates nuclear translocation of the transcription factors NF-kappa B and AP-1, but not NF-IL-6. NF-kappa B inhibitors blocked the ability of toxin A to induce IL-8 secretion, and supershift analysis indicated that the major isoform of NF-kappa B activated by the toxin is a p50-p65 heterodimer. This study is the first to identify intracellular signaling pathways and transcription factors involved in the C. difficile toxin-mediated up-regulation of IL-8 synthesis and release by target cells. This information should increase our understanding of the pathogenesis of C. difficile colitis and the nature of IL-8 gene regulation as well.
Bacterial Toxins↗
IL-18, a novel immunoregulatory cytokine, is up-regulated in Crohn's disease: expression and localization in intestinal mucosal cells.
IL-18, a novel immunoregulatory cytokine with potent IFN-gamma-inducing activities, may play an important role in Th1-mediated chronic inflammatory disorders. The aim of the present study was to characterize the expression and localization of IL-18 in colonic specimens and isolated mucosal cell populations from patients with Crohn's disease (CD), a prototypic Th1-mediated disorder. Using a semiquantitative RT-PCR protocol, IL-18 mRNA transcripts were found to be increased in freshly isolated intestinal epithelial cells (IEC) and lamina propria mononuclear cells (LPMC) from CD compared with ulcerative colitis (UC) and noninflamed control (cont) patients, and were more abundant in IEC compared with LPMC. Immunohistochemical analysis of surgically resected colonic tissues localized IL-18 to both LPMC (specifically, macrophages and dendritic cells) as well as IEC. Staining was more intense in CD compared with UC and cont, and in involved (inv) vs noninvolved (n inv) areas. Western blot analysis revealed that an 18. 3-kDa band, consistent with both recombinant and mature human IL-18 protein, was found predominantly in CD vs UC intestinal mucosal biopsies; a second band of 24 kDa, consistent with the inactive IL-18 precursor, was detected in n inv areas from both CD and UC biopsies and was the sole form found in noninflamed cont. To our knowledge, this report is the first describing increased expression of IL-18 in a human Th1-mediated chronic inflammatory disease. In addition, our studies further support the concept that IEC and dendritic cells may possess important immunoregulatory functions in both normal, as well as pathological, mucosal immunity.
Adjuvants, Immunologic↗
Schinzel-Giedion syndrome: evidence for a neurodegenerative process.
We report on a case of Schinzel-Giedion syndrome in which serial magnetic resonance (MR) brain-imaging studies demonstrated a progressive neurodegenerative process. These findings in addition to "coarse" facial appearance and skeletal abnormality suggest that a progressive metabolic defect underlies this syndrome. However, results of detailed investigations for metabolic disorder were all normal.
Abnormalities, Multiple↗
The human intracellular interleukin 1 receptor antagonist promoter appropriately regulates gene expression in keratinocytes and gastrointestinal epithelial cells in vivo.
The 4555-bp promoter fragment for intracellular interleukin 1 receptor antagonist (4555-bp icIL-1Ra) has recently been demonstrated to regulate gene expression in a cell-type specific manner in vitro in transient transfection studies. To examine the activity of this promoter in vivo, transgenic mice possessing the 4555-bp promoter coupled to the E. coli lacZ reporter gene were created. Expression of endogenous icIL-1Ra and E. coli lacZ mRNA were examined in different tissues by RT-PCR, RNase protection assay and in situ hybridization. In transgenic mice both endogenous icIL-1Ra and E. coli lacZ were co-expressed by keratinocytes and by epithelial cells in different organs of the digestive system. The transgene was also expressed in the brain in four out of five lines, whereas endogenous icIL-1Ra was not detected in this organ. In contrast, only icIL-1Ra mRNA, but not E. coli lacZ mRNA, was detected in lipopolysaccharide (LPS)-stimulated resident peritoneal macrophages from icIL-1Ra promoter transgenic mice. These results indicate that a 4555-bp promoter fragment of human icIL-1Ra appropriately regulates gene transcription in keratinocytes and gastrointestinal epithelial cells in vivo. However, other as yet unidentified regulatory regions influence icIL-1Ra gene expression in macrophages following LPS stimulation.
Animals↗
Early and late reversal of rocuronium and vecuronium with neostigmine in adults and children.
UNLABELLED: We investigated the influence of the timing of neostigmine administration on recovery from rocuronium or vecuronium neuromuscular blockade. Eighty adults and 80 children were randomized to receive 0.45 mg/kg rocuronium or 0.075 mg/kg vecuronium during propofol/fentanyl/N2O anesthesia. Neuromuscular blockade was monitored by train-of-four (TOF) stimulation and adductor pollicis electromyography. Further randomization was made to control (no neostigmine) or reversal with 0.07 mg/kg neostigmine/0.01 mg/kg glycopyrrolate given 5 min after relaxant, or first twitch (T1) recovery of 1%, 10%, or 25%. Another eight adults and eight children received 1.5 mg/kg succinylcholine. At each age, spontaneous recovery of T1 and TOF was similar after rocuronium and vecuronium administration but was more rapid in children (P < 0.05). Spontaneous recovery to TOF0.7 after rocuronium and vecuronium administration in adults was 45.7 +/- 11.5 min and 52.5 +/- 15.6 min; in children, it was 28.8 +/- 7.8 min and 34.6 +/- 9.0 min. Neostigmine accelerated recovery in all reversal groups (P < 0.05) by approximately 40%, but the times from relaxant administration to TOF0.7 were similar and independent of the timing of neostigmine administration. Recovery to T1 90% after succinylcholine was similar in adults (9.4 +/- 5.0 min) and children (8.4 +/- 1.1 min) and was shorter than recovery to TOF0.7 in any reversal group after rocuronium or vecuronium administration. Recovery from rocuronium and vecuronium blockade after neostigmine administration was more rapid in children than in adults. Return of neuromuscular function after reversal was not influenced by the timing of neostigmine administration. These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. IMPLICATIONS: These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. Although spontaneous and neostigmine-assisted recovery is more rapid in children than in adults, in neither is return of function as rapid as after succinylcholine administration.
Adult↗
Insights into the mechanism of sustained ventricular tachycardia after myocardial infarction in a closed chest porcine model using a multielectrode "basket" catheter.
INTRODUCTION: Accurate analysis of the arrhythmia substrate is important for successful radiofrequency ablation of sustained ventricular tachycardia (VT) after myocardial infarction (MI). METHODS AND RESULTS: A multielectrode "basket" catheter capable of endocardial recording and pacing was inserted percutaneously into the left ventricle of post-MI swine for analysis of the mechanism of sustained VT. Sustained VT was induced in 42 of 61 pigs that survived an acute MI produced by percutaneous transluminal coronary angioplasty balloon occlusion of the left anterior descending coronary artery and injection of agarose gel beads. A multielectrode "basket" catheter (Constellation) with 64 electrodes was inserted in 35 of these animals for analysis of the VT. Induced VT had a cycle length of 179 +/- 25 msec at control and 230 +/- 43 msec after administration of intravenous procainamide. Presystolic electrical activity was recorded from at least 1 of 32 bipolar pairs of electrodes at a mean 40.7 +/- 23.6 msec prior to QRS onset. Isolated mid-diastolic potentials were recorded in 26 of 35 animals. In 22 animals, there were multiple isolated potentials recorded from adjacent electrode pairs. Isochronal maps demonstrated that these potentials returned to the systolic site of origin. Resetting of sustained VT by single premature ventricular stimuli was observed in 6 of 12 animals. Entrainment with overdrive pacing was seen in 19 of 26 animals with induced VT. Concealed entrainment was observed in ten animals. The mean stimulus to QRS interval was 45 +/- 28 msec. Concealed entrainment was observed from adjacent electrode pairs with different stimulus to QRS intervals. CONCLUSION: These data suggest that sustained VT in this model is due to reentry with an excitable gap. A multielectrode "basket" catheter is useful for analyzing the zone of slow conduction participating in the tachycardia circuit. Such analysis may provide useful information to guide successful catheter ablation of sustained VT after MI.
Animals↗
Effect of anthelmintic treatment on sexual maturation in prepubertal beef heifers.
Heifers treated with ivermectin at weaning have been reported to reach puberty at a younger age and lighter weight than untreated heifers. We tested the hypothesis that heifers administered ivermectin would respond with earlier follicular development and a greater LH response to a 1-mg estradiol-17beta challenge (E2C) than untreated heifers. Fall-born Angus heifers (n = 32) were randomly assigned on 284 +/- 9 d of age (215.5 +/- 20.8 kg) to receive ivermectin (IVR) or albendazole (ALB), IVR + ALB, or to remain as untreated controls (CONT). Each group (n = 8) was housed separately in adjacent pens throughout the trial and managed to gain .8 kg/heifer on a ration containing 13.2% CP, 58.8% TDN, and 49.9% DM. The CONT heifers received an additional 2.27 kg/heifer of corn silage and 1.59 kg/heifer of corn daily to maintain ADG at comparable levels. Individual body weight was recorded weekly, and nematode eggs per gram (EPG) of feces were measured every 21 d. Ultrasonography was performed on alternate days starting 2 wk prior to E2C to characterize follicular wave patterns. Follicles were separated into classes (C1 [3 to 5 mm], C2 [6 to 9 mm], and C3 [10 mm]) and sizes (largest [LF], second [SLF], third [TLF], and fourth largest follicles [FLF]). The sizes of the regressing dominant follicle 1 (DF1) and the progressing dominant follicle 2 (DF2) were also determined. Serum concentrations of LH were determined from hourly jugular blood samples collected 8 to 24 h after injection of E2C. The IVR + ALB treatment group had more C3 follicles than ALB and CONT (P < .07). The IVR-treated heifers had larger TLF than ALB and CONT (P < .04). The IVR- and IVR + ALB-treated heifers had larger FLF and DF2 than ALB and CONT (P < .1). Least squares means for DF2 were 9.5 +/- .5, 8.0 +/- .4, 9.5 +/- .3 and 8.3 +/- .3 mm, for IVR, ALB, IVR + ALB and CONT, respectively (P = .02 for treatment effect). The E2C-induced serum LH concentration did not differ with respect to treatment. We conclude that heifers administered IVR display increased follicular development, supporting our earlier investigations regarding reduced age at puberty in heifers treated with IVR near weaning.
Animals↗
Cataract surgery in the glaucoma patient: advances and modifications.
Cataract removal in the glaucoma patient is a less arduous task today than it was a decade ago, because of technological advances and modifications in surgical technique. These technological advances include excellent phacoemulsification instrumentation. Useful modifications in surgical technique include the use of combined phacotrabeculectomy with antimetabolite supplementation, when necessary. Anticipated advances in the next decade include superior viscoelastics and the widespread availability of capsular tension rings.
Cataract↗
New aqueous inflow inhibitors.
Several new aqueous inflow inhibitors have been introduced over the past few years. These new agents include two alpha agonists, two topical carbonic anhydrase inhibitors, and a novel combination agent. All of these agent compare favorably with timolol in terms of aqueous suppression, though each has its own relative advantages and disadvantages.
Adrenergic alpha-Agonists↗
Results of another modality for extending glaucoma drainage tubes.
PURPOSE: For a variety of reasons, on rare occasions a surgeon needs to reposition the intraocular portion of a glaucoma drainage implant tube, but finds the tube "too short" to do so. This study describes results of a different technique for "extending" the tube (rather than replacing the entire apparatus). METHODS: Four eyes of four patients required a tube "extender," for either tube tip blockage associated with uncontrolled intraocular pressure (IOP; n = 3), or to avoid total seton replacement after tube "cheesewiring" (n = 1). An extender was fashioned from common angiocatheter material. Postoperative complications, IOP, and need for further surgery were reviewed. RESULTS: None of the four patients required further, more invasive surgery or experienced any related postoperative complications. Final IOP averaged 11.5 +/- 4.2 mmHg (range 6-16 mmHg). CONCLUSION: Tube extension using angiocatheter material is a viable, cost-effective option in these difficult cases, saving the surgeon from having to explant and replace the entire implant.
Aged↗
Regulation of ovarian extracellular matrix remodelling by metalloproteinases and their tissue inhibitors: effects on follicular development, ovulation and luteal function.
In most organs, remodelling of tissues after morphogenesis is minimal; however, normal ovarian function depends upon cyclical remodelling of the extracellular matrix (ECM). The ECM has a profound effect on cellular functions and probably plays an important role in the processes of follicular development and atresia, ovulation, and development, maintenance and regression of corpora lutea. Matrix metalloproteinases (MMPs; collagenases, gelatinases, stromelysins and membrane-type MMPs) cleave specific components of the ECM and are inhibited by tissue inhibitors of metalloproteinases (TIMPs). MMPs have been detected at all stages of follicular development and probably modulate follicular expansion or atresia within the ovarian stroma. In addition, increased MMP activity appears to be required for ovulation since follicular rupture occurred in the absence of plasminogen activator activity and inhibitors of MMPs blocked follicular rupture. Development and luteolysis of the corpus luteum are accompanied by extensive remodelling of the ECM. Differentiation and regression of luteal cells are associated with construction and degradation of ECM, respectively. There is increasing evidence that ECM components enhance luteinization; whereas loss of ECM results in luteal cell death. Ovine large luteal cells may be the primary type of cell responsible for controlling the extent of remodelling of luteal ECM since they produce TIMP-1, TIMP-2 and plasminogen activator inhibitor 1. The ratio of active MMPs to TIMPs may be important in maintaining an ECM microenvironment conducive to the differentiation of follicular-derived cells into luteal cells, and maintenance of the phenotype of luteal cells.
Animals↗
Intraocular pressure reduction following phacoemulsification cataract extraction with posterior chamber lens implantation in glaucoma patients.
BACKGROUND AND OBJECTIVE: To evaluate changes in intraocular pressure (IOP) following uneventful phacoemulsification cataract extraction with posterior chamber intraocular lens implantation (Phaco/PC IOL) in primary open-angle glaucoma (POAG) patients. PATIENTS AND METHODS: The authors retrospectively reviewed preoperative and postoperative IOP in 31 consecutive medically-controlled POAG patients who underwent uneventful Phaco/PC IOL. None of the patients had prior intraocular surgery. RESULTS: The mean preoperative IOP in the POAG group was 18.1+/-3.1 mm Hg with patients receiving a mean of 1.7 antiglaucoma medications. With a mean follow-up of 16.4 months, the average postoperative IOP in the POAG group was 15.2+/-2.9 mm Hg (P < .001, Student's t test) with patients receiving a mean of 0.7 antiglaucoma medication (P < .001). CONCLUSION: Phaco/PC IOL may be associated with a significant decrease in IOP in POAG patients, allowing for decreased postoperative antiglaucoma medication.
Aged↗
First-trimester growth and the risk of low birth weight.
BACKGROUND: Previous studies have demonstrated a correlation between first-trimester size and birth weight. It is not known, however, whether low birth weight is related to first-trimester growth. We sought to determine whether the risk of low birth weight and birth weight that was low for gestational age is related to the size of the embryo or the fetus in the first trimester. METHODS: From a data base of ultrasound records of more than 30,000 pregnancies, we identified women who had no important medical problems, a normal menstrual history, and a first-trimester ultrasound scan in which the crown-rump length of the embryo or fetus had been measured. We examined the relation between the outcome of 4229 pregnancies and the difference between the measured and the expected crown-rump length in the first trimester, expressed as equivalent days of growth. RESULTS: A first-trimester crown-rump length that was two to six days smaller than expected was associated with an increased risk (as compared with a normal or slightly larger than expected crown-rump length) of a birth weight below 2500 g (relative risk, 1.8; 95 percent confidence interval, 1.3 to 2.4), a birth weight below 2500 g at term (relative risk, 2.3; 95 percent confidence interval, 1.4 to 3.8), a birth weight below the fifth percentile for gestational age (relative risk, 3.0; 95 percent confidence interval, 2.0 to 4.4), and delivery between 24 and 32 weeks of gestation (relative risk, 2.1; 95 percent confidence interval, 1.1 to 4.0), but not with delivery between 33 and 36 weeks (relative risk, 1.0; 95 percent confidence interval, 0.7 to 1.5). CONCLUSIONS: Suboptimal first-trimester growth may be associated with low birth weight, low birth-weight percentile, and premature delivery.
Birth Weight↗