Insulin-like growth factor I administration in young rats with acute renal failure

The outcome of ischemic acute renal failure (IARF) is better in young than adult rats. Insulin-like growth factor I (IGF-I) treatment may increase mortality of adult rats with IARF, probably because of an exaggerated inflammatory response. We report the response to IGF-I therapy in young rats with IARF. Male rats, aged 28+/-1 days, with IARF were given subcutaneous IGF-I, 50 microg/100 g at 0, 8, and 16 h after reperfusion (IGF) or were untreated (ARF). Sham-operated rats were used as controls. At 2 and 7 days after ischemia, serum urea nitrogen and histological damage score, cell proliferation, apoptosis, neutrophil infiltration, and IGF-I receptor mRNA in kidneys were analyzed. The degree of renal failure, mortality rate, histological damage, cell proliferation, and neutrophil infiltration were not different between IGF-I and ARF rats. Hence, short-term IGF-I treatment did not modify the course of IARF in young rats.     

Propofol-ketamine versus propofol-fentanyl for outpatient laparoscopy: comparison of postoperative nausea,emesis, analgesia,and recovery

STUDY OBJECTIVE: To compare postoperative nausea, emesis, analgesia, and recovery between propofol-ketamine and propofol-fentanyl in outpatient laparoscopic tubal ligations with general anesthesia. STUDY DESIGN: Prospective, randomized, blinded study. SETTING: Tertiary-care women's hospital. PATIENTS: 120 ASA physical status I and II ambulatory patients scheduled for elective laparoscopic tubal ligation. INTERVENTIONS: Patients were randomized to two groups to receive either ketamine (1-1.5 mg/kg) or fentanyl (3-5 microg/kg). MEASUREMENTS: Measured variables included total dose of ketamine, fentanyl, propofol, and operating time. Vital signs, pain visual analog scale scores (VAS), nausea VAS, presence of emesis, treatment for nausea and vomiting, pruritus, sedation, and presence of dreaming were recorded on postanesthesia care unit (PACU) admission, PACU discharge, stepdown unit admission, and hospital discharge. Results are expressed as means +/- SD or medians and analyzed using t-test, Chi-square, or Mann-Whitney (p < 0.05). MAIN RESULTS: No differences were noted with respect to propofol dose, operating times, pain or nausea VAS scores, emesis, treatment for nausea and vomiting, pruritus, and sedation on PACU admission, PACU discharge, stepdown unit admission, and hospital discharge. The ketamine group had a higher heart rate, required more pain medication, and had a higher frequency of dreaming on PACU admission than the fentanyl group. These differences became insignificant on PACU discharge. CONCLUSIONS: For outpatient laparoscopic tubal ligations with general anesthesia, propofol-ketamine does not improve postoperative nausea, emesis, analgesia or recovery compared with the propofol-fentanyl combination.     

Keratocyte density of central human cornea after laser in situ keratomileusis

PURPOSE: To determine changes in keratocyte density in the first year after laser in situ keratomileusis (LASIK). DESIGN: Prospective interventional cohort study. METHODS: Seventeen eyes of 11 patients received LASIK with a planned 180-microm flap to correct refractive errors between -2.0 diopters and -11.0 diopters. Images of the full-thickness cornea were obtained by using confocal microscopy in vivo before LASIK and at 1 week, 1, 3, 6, and 12 months after LASIK. Bright objects (that resembled keratocytes) in images without motion blur were manually counted by one observer. Cell densities were determined in anterior and posterior halves of the stromal flap, anterior and posterior halves of the layer 100 microm-thick immediately deep to the ablation (retroablation layer), and in the posterior third of the stroma. The region of stroma that was ablated (as measured 1 month after LASIK) was omitted from the preoperative analysis. RESULTS: Keratocyte density in the anterior flap was 28,978 +/- 5849 cells/mm(3) (mean +/- SD) pre-LASIK, and was decreased at all postoperative examinations, but the difference was not significant until 12 months after LASIK (22% decrease). Keratocyte densities in the posterior flap were 20,397 +/- 4215 cells/mm(3) pre-LASIK and were decreased by 20%-40% at all postoperative examinations 1 week to 1 year after LASIK. Keratocyte densities in the anterior half of the retroablation layer were 16,605 +/- 3595 cells/mm(3) pre-LASIK and decreased by 16%-30% between 3 and 12 months after LASIK. Keratocyte densities in the posterior half of the retroablation layer and posterior stroma did not change. CONCLUSIONS: Keratocyte densities in the posterior flap and anterior retroablation layer (regions adjacent to the lamellar cut) decrease at 1 week and 3 months, respectively, after LASIK and remain decreased in these regions at 12 months after LASIK. In the anterior flap, keratocyte density decreases 1 year after LASIK. The long-term effects of these cellular deficits, if any, require further study.     

Effect of myopic laser in situ keratomileusis on epithelial and stromal thickness: a confocal microscopy study

PURPOSE: To determine changes in central epithelial and stromal thickness in human corneas in vivo after laser in situ keratomileusis (LASIK). DESIGN: Prospective, nonrandomized, comparative trial. PARTICIPANTS: Eighteen eyes of 12 patients received LASIK (performed using the VISX Star laser [VISX, Santa Ana, CA]) with a planned 180- micro m flap (created using an automated Hansatome microkeratome [Bausch & Lomb, Irvine, CA]) to correct refractive errors between -2.0 diopters (D) and -11.0 D. METHODS: Corneas were examined by using confocal microscopy in vivo before LASIK and at 1 week and 1, 3, 6, and 12 months after LASIK. Epithelial thickness was the distance between images of the surface epithelium and subbasal nerve plexus or, when nerves were not visible, the subbasal peak (if present in the light intensity profile). Total flap thickness was the distance between images of the surface epithelium and interface debris (or peak), and total stromal thickness was the distance between images of the most anterior keratocytes and endothelium. MAIN OUTCOME MEASURES: Corneal epithelial and stromal thickness. RESULTS: Epithelial thickness before LASIK was 46 +/- 5 micro m (mean +/- standard deviation) and increased 22% by 1 month after LASIK (56 +/- 5 micro m; P = 0.01). Thereafter, epithelial thickness did not change, but remained thicker at 12 months after LASIK (54 +/- 8 micro m) than before LASIK (P = 0.02). Total flap thickness at 1 month after LASIK was 160 +/-28 micro m and did not change thereafter. Changes in total stromal thickness between 1 and 12 months after LASIK were not significant. CONCLUSIONS: The central corneal epithelium was thicker in the first year after LASIK than before LASIK. There was no change in central stromal thickness between 1 month and 12 months after LASIK.     

Quantification of interpoint topographic correlations of threshold values in glaucomatous visual fields

PURPOSE: The authors sought to quantify neighboring and distant interpoint correlations of threshold values within the visual field in patients with glaucoma. METHODS: Visual fields of patients with confirmed or suspected glaucoma were analyzed (n = 255). One eye per patient was included. Patients were examined using the 32 program of the Octopus 1-2-3. Linear regression analysis among each of the locations and the rest of the points of the visual field was performed, and the correlation coefficient was calculated. The degree of correlation was categorized as high (r(2) > 0.66), moderate (0.66 > or = r(2) > 0.33), or low (r(2) < or = 0.33). The standard error of threshold estimation was calculated. RESULTS: Most locations of the visual field had high and moderate correlations with neighboring points and with distant locations corresponding to the same nerve fiber bundle. Locations of the visual field had low correlations with those of the opposite hemifield, with the exception of locations temporal to the blind spot. The standard error of threshold estimation increased from 0.6 to 0.9 dB with an r(2) reduction of 0.1. CONCLUSION: Locations of the visual field have highest interpoint correlation with neighboring points and with distant points in areas corresponding to the distribution of the retinal nerve fiber layer. The quantification of interpoint correlations may be useful in the design and interpretation of visual field tests in patients with glaucoma.     

Neuroprotective effects of brimonidine against transient ischemia-induced retinal ganglion cell death: a dose response in vivo study

The purpose of this study was to investigate the dose-response effects of topically administered brimonidine (BMD) on retinal ganglion cell (RGC) survival, short and long periods of time after transient retinal ischemia. In adult Sprague-Dawley rats, RGCs were retrogradely labeled with the fluorescent tracer fluorogold (FG) applied to both superior colliculi. Seven days later, the left ophthalmic vessels were ligated for 90 min. One hr prior to retinal ischemia, two 5 microl drops of saline alone or saline containing 0.0001, 0.001, 0.01 or 0.1% BMD were instilled on the left eye. Rats were processed 7, 14 or 21 days later and densities of surviving RGCs were estimated by counting FG-labeled RGCs in 12 standard regions of each retina. The following have been found. (1) Seven days after 90 min of transient ischemia there is loss of approximately 46% of the RGC population. (2) topical pre-treatment with BMD prevents ischemia-induced RGC death in a dose-dependent manner. Administration of 0.0001% BMD resulted in the loss of approximately 37% of the RGC population and had no significant neuroprotective effects. Administration of higher concentrations of BMD (0.001 or 0.01%) resulted in the survival of 76 or 90%, respectively, of the RGC population, and 0.1% BMD fully prevented RGC death in the first 7 days after ischemia. (3) Between 7 and 21 days after ischemia there was an additional slow cell loss of approximately 25% of the RGC population. Pre-treatment with 0.1% BMD also reduced significantly this slow cell death. These results indicate that the neuroprotective effects of BMD, when administered topically, are dose-dependent and that the 0.1% concentration achieves optimal neuroprotective effects against the early loss of RGCs. Furthermore, this concentration is also effective to diminish the protracted loss of RGCs that occurs with time after transient ischemia.     

N-acetyltransferase 2 single-nucleotide polymorphisms and risk of gastric carcinoma

OBJECTIVE: To explore whether an association exists between the NAT2 genotype and the risk of developing gastric cancer.METHODS. Ninety-nine patients with gastric adenocarcinoma and 258 healthy subjects were analysed for single-nucleotide polymorphisms at the NAT2 gene locus, which give rise to gene variants known to be associated with slow-acetylation status.RESULTS: The functional NAT2*4 (wild-type) allele is over-represented among patients (40.4% of all allelic variants) compared with control subjects [25.8%, odds ratio (OR) 1.95, 95% confidence interval (CI) 1.36, 2.8]. According to the NAT2 genotype, 69 patients (69.9%) and 119 healthy subjects (46%) were classified as rapid acetylators (OR 2.69, 95% CI 1.6, 4.54).CONCLUSIONS: Our results, which need independent confirmation, suggest that individuals with NAT2 genotypes leading to high levels of NAT2 enzyme activity are at increased risk of developing gastric carcinoma.     

Biochemical characterization of rhinovirus RNA-dependent RNA polymerase

Human rhinoviruses (HRV) represent the single most important causative agent of the common cold. The HRV genome encodes an RNA-dependent RNA polymerase (RdRp) designated 3D polymerase that is required for replication of the HRV RNA genome. We have expressed and purified recombinant HRV-16 3D polymerase to near homogeneity from Escherichia coli transformed with an expression plasmid containing the full-length 460 amino acid HRV-16 3D sequence with a methionine at the N-terminus and a glycine-serine linker followed by a 6-histidine affinity tag at the C-terminus. The purified recombinant protein has rifampicin-resistant activity in a poly(A)-dependent poly(U) polymerase assay while corresponding fractions similarly purified from E. coli transformed with an expression plasmid without the HRV-16 3D sequence showed no activity. The optimal conditions for temperature, pH, divalent cations Mg(2+) and Mn(2+), and KCl were determined. The recombinant protein has RNA polymerase activity on homopolymeric templates poly(A) and poly(C) and heteropolymeric RNA templates primed with either RNA or DNA oligonucleotide primers or self-primed by a copy-back mechanism. A unique, secondary structureless heteropolymeric RNA template that is an efficient substrate was developed to facilitate kinetic characterizations of the enzyme. In the presence of Mg(2+), the enzyme displayed strong base and sugar specificity. However, when Mg(2+) was replaced by Mn(2+) specificity for ribonucleotides was lost, utilization of deoxynucleotides became possible and primer-independent activity was observed on the poly(C) template. Zn(2+) was found to inhibit HRV-16 3D polymerase with an IC(50) as low as 0.6 microM by a mechanism distinct from the magnesium ion stimulation. The activity of this 6His-tagged HRV-16 3D polymerase was compared with that of a recombinant HRV-16 3D polymerase expressed without the 6His-tag and was found to be identical. The availability of recombinant rhinovirus RdRp in a purified form will facilitate the structure-function analysis of this enzyme as well as the identification of specific inhibitors to the rhinovirus 3D polymerase that have therapeutic value in the treatment of the common cold.