Treated threshold stage 3 versus spontaneously regressed subthreshold stage 3 retinopathy of prematurity: a study of motility, refractive, and anatomical outcomes at 6 months and 36 months

AIM: To compare the visual acuity (VA), spherical equivalent refractive error, motility, and anatomical outcomes in children with treated regressed threshold stage 3 retinopathy of prematurity (ROP) and those with spontaneously regressed subthreshold stage 3 ROP. METHOD: 6 month and 3 year data collected from infants examined between 1989 and 1999 with regressed stage 3 ROP, with or without treatment were retrospectively reviewed. RESULTS: 85 infants were included in this study. 40 eyes received cryotherapy, 81 eyes laser photocoagulation, and 34 eyes had spontaneously regressed subthreshold stage 3 ROP. Grating acuity score > or =2 cycles/degree (c/d) at 6 months was predictive of optotype acuity > or =6/9 in 69% of eyes and a score <2 c/d at 6 months was predictive of acuity < 6/9 in 88% of eyes. Eyes with subthreshold stage 3 ROP were twice as likely to have VA of 6/9 or better at 36 months than the treated eyes. The mean spherical equivalent refractive error at 36 months was -6.5 dioptres (D) (-21.5D to +1.38D) in cryotherapy treated eyes, -2.4D (-13D to +4D) in the laser group, and -0.22D (-9D to +2.25D) in the subthreshold group. Eyes within the treated groups were more myopic than the eyes within the spontaneously regressed group (p = 0.005). At 36 months, 42 out of the 85 infants (that is, 49%) had strabismus (44% in the cryotherapy group, 26% in the laser group, and 25% in the subthreshold group). There was a statistically significant association between the presence of strabismus and anisometropia (p = 0.016) and strabismus and intraventricular haemorrhage (IVH) (p = 0.005). There was a statistically significant difference in the incidence of strabismus between mild and moderate and severe grade IVH (p = 0.01). Eight out of 40 eyes in the cryotherapy group and six out of the 81 eyes in the laser group developed macular ectopia. None of the eyes in the spontaneously regressed group had macular dragging. CONCLUSIONS: In this study, the grating acuity at 6 months was a good predictor of the 3 year optotype acuity in all groups. Eyes with spontaneously regressed subthreshold stage 3 ROP were associated with better vision at 3 years of age and a lesser degree of myopia compared to the treated groups. Strabismus developed predominantly in the treated groups and was frequently associated with neurological damage and/or anisometropia. The spontaneously regressed subthreshold stage 3 group had a better anatomical outcome compared to the groups in which the retinopathy regressed following treatment.     

Age-related trends in gene expression in the chemosensory-nasal mucosae of senescence-accelerated mice

We have utilized high-density GeneChip oligonucleotide arrays to investigate the use of the senescence-accelerated mouse (SAM) as a biogerontological resource to identify patterns of gene expression in the chemosensory-nasal mucosa. Gene profiling in chronologically young and old mice of the senescence-resistant (SAMR) and senescence-prone (SAMP) strains revealed 133 known genes that were modulated by a three-fold or greater change either in one strain or the other or in both strains during aging. We also identified known genes in our study which based on their encoded proteins were identified as aging-related genes in the aging neocortex and cerebellum of mice as reported by Lee et al. (2000) [Nat. Genet. 25 (2000) 294]. Changes in gene profiles for chemosensory-related genes including olfactory and vomeronasal receptors, sensory transduction-associated proteins, and odor and pheromone transport molecules in the young SAMR and SAMP were compared with age-matched C57BL/6J mice. An analysis of known gene expression profiles suggests that changes in the expression of immune factor genes and genes associated with cell cycle progression and cell death were particularly prominent in the old SAM strains. A preliminary cellular validation study supported the dysregulation of cell cycle-related genes in the old SAM strains. The results of our initial study indicated that the use of the SAM models of aging could provide substantive information leading to a more fundamental understanding of the aging process in the chemosensory-nasal mucosa at the genomic, molecular, and cellular levels.     

Role of neuropeptide Y in the regulation of gonadotropin releasing hormone system in the forebrain of Clarias batrachus (Linn.): immunocytochemistry and high performance liquid chromatography-electrospray ionization-mass spectrometric analysis

Although the importance of neuropeptide Y (NPY) in the regulation of gonadotropin releasing hormone (GnRH) and reproduction has been highlighted in recent years, the neuroanatomical substrate within which these substances might interact has not been fully elucidated. Present work was undertaken with a view to define the anatomical-physiological correlates underlying the role exercised by NPY in the regulation of GnRH in the forebrain of the teleost Clarias batrachus. Application of double immunocytochemistry revealed close associations as well as colocalizations of the two peptides in the olfactory receptor neurons (ORNs), olfactory nerve fibers and their terminals in the glomeruli, ganglion cells of nervus terminalis, medial olfactory tract, fibers in the area ventralis telencephali/pars supracommissuralis and cells as well as fibers in the pituitary. NPY containing axons were found to terminate in the vicinity of GnRH cells in the pituitary with light as well as electron microscopy. Double immunoelectron microscopy demonstrated gold particles for NPY and GnRH colocalized on the membrane and in dense core of the secretory granules in the cells distributed in all components of the pituitary gland. To assess the physiological implication of these observations, NPY was injected via the intracranial route and the response of GnRH immunoreactive system was evaluated by relative quantitative morphometry as well as high performance liquid chromatography (HPLC) analysis. Two hours following NPY (20 ng/g body weight) administration, a dramatic increase was observed in the GnRH immunoreactivity in the ORNs, in the fibers of the olfactory bulb (163%) and medial olfactory tract (351%). High performance liquid chromatography-electrospray ionization-mass spectrometric analysis confirmed the immunocytochemical data. Significant rise in the salmon GnRH (sGnRH)-like peptide content was observed in the olfactory organ (194.23%), olfactory bulb (146.64%), telencephalon+preoptic area (214.10%) and the pituitary (136.72%) of the NPY-treated fish. However, GnRH in the hypothalamus was below detection limit in the control as well as NPY-treated fish. Present results suggest the involvement of NPY in the up-regulation of sGnRH containing system at different level of neuraxis extending from the olfactory epithelium to the pituitary in the forebrain of C. batrachus.     

CSF cytokine levels in preterm infants may reflect systemic inflammation and are independent of gestation

Background

Among preterm infants, high concentrations of inflammatory mediators in cerebrospinal fluid (CSF) are associated with poor outcome. Previous studies have not indicated whether CSF concentrations of inflammatory mediators are associated with important confounders such as gestational age.

Aims

To examine associations between CSF concentrations of inflammatory mediators and gestational age, maternal features suggestive of inflammation, characteristics of the CSF sample or the presence of a systemic inflammatory response.

Study design and subjects

Aliquots of CSF obtained during routine investigation of potential sepsis among infants born before 35 weeks gestation were assayed for 17 mediators of inflammation using a fluorescent multi-bead analyser. Other information was collected from routine clinical records.

Results

39 infants were assessed. CSF levels of mediators of inflammation were not correlated with gestational age. CSF red blood cell counts were correlated with CSF concentrations of IL-6, GM-CSF and IL-17 (each p < 0.003). CSF lactate was correlated with CSF concentrations of IL-1β, IL-6, GM-CSF, G-CSF, IFN-γ and MIP-1β. CSF concentrations of IL-1β, IL-6, G-CSF, TNF-α and IFN-γ were higher in infants with a raised CRP within 24 h of delivery (each p < 0.003).

Conclusions

CSF concentrations of inflammatory mediators most probably reflect inflammatory pathologies and are not influenced by gestational age. They may also, however, reflect contamination with blood or systemic inflammation. CSF concentrations of inflammatory mediators may not provide a specific indicator of CNS inflammation.     

Telomere length dynamics differ in foetal and early post-natal human leukocytes in a longitudinal study

Haemopoietic stem cells (HSC) undergo a process of self renewal to constantly maintain blood cell turnover. However, it has become apparent that adult HSC lose their self-renewal ability with age. Telomere shortening in peripheral blood leukocytes has been seen to occur with age and it has been associated with loss of HSC proliferative capacity and cellular ageing. In contrast foetal HSC are known to have greater proliferative capacity than post-natal stem cells. However it is unknown whether they undergo a similar process of telomere shortening. In this study we show a more accentuated rate of telomere loss in leukocytes from pre term infants compared to human foetuses of comparable age followed longitudinally for 8–12 weeks in a longitudinal study. Our results point to a difference in HSC behaviour between foetal and early postnatal life which is independent of age but may be influenced by events at birth itself. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Antibodies to hepatitis C virus in autologous blood donors

Hepatitis C virus (HCV) is the major cause of posttransfusion hepatitis. Two anti-HCV enzyme immunoassay (EIA) kits and one recombinant immunoblot assay (RIBA) were used to test serum samples of 1476 donations from 692 autologous blood donors to assess the prevalence of anti-HCV and its relationship to transfusion history. Of all autologous blood donations, 23 (1.6%) reacted when tested with one EIA kit and 29 (2.0%) reacted when tested by the other EIA kit. Of the autologous donors, 12 (1.78%) reacted by the first EIA kit and 14 (2.02%) by the second. Discrepancies in the EIA results from different donations by the same donor were seen in seven donors. The RIBA was positive or indeterminate in 33 percent of the EIA-reactive donations and in 41 percent of EIA-reactive donors. All RIBA-positive and -indeterminate samples reacted with both EIA kits. There was no significant difference in the EIA-reactive rates of autologous and first-time homologous blood donors. Previously transfused autologous blood donors had a higher anti-HCV EIA-reactive rate than nontransfused autologous donors, but the difference was not significant. In regard to hepatitis C, the use of autologous blood for homologous transfusion appears to be as safe as the use of blood from first-time homologous donors. Universal testing of previously transfused patients for hepatitis C appears premature at this time. Discrepant anti-HCV EIA results from different donations from the same individual have implications regarding donor deferral.     

Population pharmacokinetics of enfuvirtide in HIV-1-infected pediatric patients over 48 weeks of treatment

The objective of this study was to characterize the population pharmacokinetics of enfuvirtide in HIV-1-infected children and adolescents. HIV-infected patients received combination antiretroviral therapy, including enfuvirtide 2.0 mg/kg subcutaneously, twice daily. Serial and trough blood samples were collected up to 48 weeks. NONMEM was used for population pharmacokinetic analysis. Enfuvirtide exposure was calculated from individual parameter estimates derived from the final model. A total of 218 samples from 43 patients were included in the analysis. Enfuvirtide plasma concentration-time data were described by a 1-compartment model with first-order absorption and elimination. The addition of each subject's actual body weight as a covariate affected CL/F but not V/F or K(a). The population CL/F, V/F, and K(a) for a 33-kg reference patient was 1.31 L/h, 2.31 L, and 0.105 h(-1), respectively. The final model was CL/F (L/h) = 1.31 . (body weight/33 [kg])(0.721). Age did not affect enfuvirtide exposure. These results confirm the appropriateness of body weight-based pediatric enfuvirtide dosing.     

Immunohistochemical localization and biochemical changes in catalase and superoxide dismutase during metamorphosis in the olfactory system of frog Microhyla ornata

Amphibian metamorphosis is characterized by rapid tissue remodeling and drastic changes in the body structure and function. Like other organs, olfactory system also undergoes a dramatic rearrangement as the animal experiences transition from aquatic to terrestrial habitat. Reactive oxygen species (ROS) are known to play an important role during anuran metamorphosis and role of antioxidant enzymes like catalase and superoxide dismutase (SOD) are believed to play a major role in these processes. Therefore, we hypothesize that antioxidant enzymes in the olfactory system may undergo changes that reflect metamorphic processes. Immunohistochemical study revealed the presence of catalase and SOD in the olfactory receptor neurons and also granular reaction in olfactory epithelium of medial diverticulum during metamorphosis. Catalase and SOD immunoreactivity were seen in the epithelium of lateral diverticulum, vomeronasal organ as metamorphosis proceeds and in the apical lining of olfactory epithelium of adult frog. Biochemical study showed that catalase activity gradually increases in the olfactory system from metamorphic stage 40-46 and adult, while SOD activity decreases from stage 40 to 46 and increases in adult. Thus, the localization and relative levels of catalase and SOD during metamorphosis in the olfactory system suggests that these enzymes may be involved in protection from oxidative damage.