Case Report: A Rare Presentation of NSAID-Induced Secondary Membranous Nephropathy in a Pediatric Patient.

Background: Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults, but it is responsible for <5% of nephrotic syndrome cases in children. MN has primary and secondary forms. Secondary MN is caused by viral infections, autoimmune diseases like lupus, or drugs. Non-steroid anti-inflammatory drug (NSAID)-induced secondary MN is rarely described in the pediatric population. Thus, the clinical presentation and time to recovery are vastly unknown in the pediatric subgroup. Clinical Presentation: We report a case of a 15-year-old female who presented with acute onset of nephrotic range proteinuria, significant hypoalbuminemia, hyperlipidemia, and lower extremity edema related to the presence of nephrotic syndrome. She had a history of ibuprofen use periodically for 6 months before presentation because of menstrual cramps and intermittent lower abdominal pain. After the presentation, we performed a renal biopsy that reported stage 1-2 MN, likely secondary. The phospholipase A2 receptor (PLA2R) antibody on the blood test and PLA2R immune stain on the renal biopsy sample were negative. We performed a comprehensive evaluation of the viral and immune causes of secondary MN, which was non-revealing. She had stopped ibuprofen use subsequent to the initial presentation. She was prescribed ACE inhibitor therapy. After 6 months of ACE inhibitor treatment, the proteinuria had resolved. Conclusion: Proteinuria can last for several weeks when NSAID induces secondary MN and nephrotic syndrome. With the widespread use of NSAIDs prevalent in the pediatric community, further studies are needed to evaluate and study the role of NSAIDs in this condition.

HIV Knowledge and Preferences for HIV Prevention Among Older Adults Living in the Community.

The purpose of this study was to explore HIV/AIDS knowledge, perceived HIV susceptibility and severity, as well as barriers and facilitators to HIV prevention in primary care settings. Data were collected through both survey and semi-structured interviews. A total of 145 adults over the age of 50 participated in the study. We found that most older adults are willing to have discussions about HIV with their health care provider, however, they are waiting for their provider to broch the topic. The study findings also indicate that older adults need additional education regarding HIV/AIDS, particularly older adults need education about methods of transmission of HIV. Based on the results of this study, it is clear that changes to HIV-related policies and practices must take place to facilitate HIV prevention in primary care settings for older adults.

On the Error State Selection for Stationary SINS Alignment and Calibration Kalman Filters-Part II: Observability/Estimability Analysis.

This paper presents the second part of a study aiming at the error state selection in Kalman filters applied to the stationary self-alignment and calibration (SSAC) problem of strapdown inertial navigation systems (SINS). The observability properties of the system are systematically investigated, and the number of unobservable modes is established. Through the analytical manipulation of the full SINS error model, the unobservable modes of the system are determined, and the SSAC error states (except the velocity errors) are proven to be individually unobservable. The estimability of the system is determined through the examination of the major diagonal terms of the covariance matrix and their eigenvalues/eigenvectors. Filter order reduction based on observability analysis is shown to be inadequate, and several misconceptions regarding SSAC observability and estimability deficiencies are removed. As the main contributions of this paper, we demonstrate that, except for the position errors, all error states can be minimally estimated in the SSAC problem and, hence, should not be removed from the filter. Corroborating the conclusions of the first part of this study, a 12-state Kalman filter is found to be the optimal error state selection for SSAC purposes. Results from simulated and experimental tests support the outlined conclusions.

Neurodegeneration and Glial Response after Acute Striatal Stroke: Histological Basis for Neuroprotective Studies.

Stroke is a leading cause of death and neurological disability worldwide and striatal ischemic stroke is frequent in humans due to obstruction of middle cerebral artery. Several pathological events underlie damage progression and a comprehensive description of the pathological features following experimental stroke in both acute and chronic survival times is a necessary step for further functional studies. Here, we explored the patterns of microglial activation, astrocytosis, oligodendrocyte damage, myelin impairment, and Nogo-A immunoreactivity between 3 and 30 postlesion days (PLDs) after experimental striatal stroke in adult rats induced by microinjections of endothelin-1 (ET-1). The focal ischemia induced tissue loss concomitant with intense microglia activation between 3 and 14 PLDs (maximum at 7 PLDs), decreasing afterward. Astrocytosis was maximum around 7 PLDs. Oligodendrocyte damage and Nogo-A upregulation were higher at 3 PLDs. Myelin impairment was maximum between 7 and 14 PLDs. Nogo-A expression was higher in the first week in comparison to control. The results add important histopathological features of ET-1 induced stroke in subacute and chronic survival times. In addition, the establishment of the temporal evolution of these neuropathological events is an important step for future studies seeking suitable neuroprotective drugs targeting neuroinflammation and white matter damage.

Uptake of the Perinatal Society of Australia and New Zealand perinatal mortality audit guideline.

BACKGROUND: Deficiencies in investigation and audit of perinatal deaths result in loss of information thereby limiting strategies for future prevention. The Perinatal Society of Australia and New Zealand (PSANZ) developed a clinical practice guideline for perinatal mortality in 2004. AIMS: To determine the current use and views of the PSANZ guideline, focussing on the investigation and audit aspects of the guideline. METHODS: A telephone survey was conducted of lead midwives and doctors working in birth suites of maternity hospitals with over 1000 births per annum in Australia and New Zealand. RESULTS: Sixty-nine of the 78 eligible hospitals agreed to participate. A total of 133 clinicians were surveyed. Only 42% of clinicians surveyed were aware of the guideline; more midwives than doctors were aware (53 vs 28%). Of those, only 19% had received training in their use and 33% reported never having referred to them in practice. Implementation of even the key guideline recommendations varied. Seventy per cent of respondents reported regularly attending perinatal mortality audit meetings; midwives were less likely than doctors to attend (59 vs 81%). Almost half (45%) of those surveyed reported never receiving feedback from these meetings. The majority of clinicians surveyed agreed that all parents should be approached for consent to an autopsy examination of the baby; however, most (86%) reported the need for clinician training in counselling parents about autopsy. CONCLUSIONS: Effective implementation programmes are urgently required to address suboptimal uptake of best practice guidelines on perinatal mortality audit in Australia and New Zealand.

Brote de enfermedad alimentaria en la localidad de El Huecú, provincia de Neuquén / Foodborne disease outbreak in El Huecú community, province of Neuquén

En febrero de 2006 ocurrió un brote epidémico de gastroenteritis aguda de origen alimentario, en ocasión de un festejo popular en una pequeña localidad de la provincia de Neuquén, Argentina. Aproximadamente 800 personas participaron de un almuerzo en las instalaciones del Gimnasio Municipal, y unas tres horas después de finalizado, cerca de 150 asistentes consultaron al hospital local, afectados por síndrome gastroentérico agudo. Se realizó una investigación epidemiológica caso-control a través de un muestreo representativo no probabilístico. Los resultados epidemiológicos establecieron un brote de ETA a fuente común, con una relación caso-control de 1:1,8. Los principales síntomas fueron cólicos abdominales (88%), vómitos (73,5%) y diarrea (60%). La torta que se sirvió en ese evento fue identificada como el alimento causal (OR 9,79; IC 95%; 2,66-36,00; valor p = 0,0001), sujeto a condiciones higiénico-sanitarias insatisfactorias en los diferentes procesos de elaboración, conservación y manipulación. De una porción de la torta se aisló una cepa de Staphylococcus aureus subespecie aureus, coagulasa positiva, enterotoxigénica, con un recuento de 2,4x10(6) UFC/g, y también se aisló este microorganismo de tres muestras de manos y narinas de personas involucradas en la preparación y el servicio. Las cepas aisladas de un operador y de la torta portaron el gen sea y presentaron el mismo patrón de SmaI-PFGE. Se atribuyó el brote de ETA a la contaminación durante el proceso de preparación de la torta consumida durante ese almuerzo popular, lo que podría estar relacionado con deficiencias en aspectos higiénicos y con la falta de refrigeración y de mantenimiento de la cadena de frío.

In the summer of 2006, an epidemic outbreak of acute gastrointestinal illness related to food consumption occurred in a small town in the province of Neuquén, Argentina. During a popular feast, approximately 800 local residents attended lunch held in the facilities of the Municipal Gymnasium. About three hours later, nearly 150 attendees sought medical assistance at the local hospital due to acute gastroenteritis. A case-control epidemiological investigation was conducted using representative non-probability sampling. The epidemiological investigation showed a common-source foodborne disease outbreak with a case-control ratio of 1:1.8. The main symptoms were abdominal cramps (88%), vomiting (73.5%) and diarrhea (60%). The cake was identified as the source of infection (OR 9.79; IC 95%, 2.66-36.00; p = 0.0001), and unsatisfactory hygienic conditions in food production, conservation and handling steps were identified. Coagulase positive, enterotoxigenic Staphylococcus aureus, subspecies aureus was detected in a piece of cake, with a count of 2.4x10(6) CFU/g, and in samples from the hands and nostrils of three people involved in food preparation and service. The strains isolated from both the cake and one of the food handlers carried the sea gene, and presented the same SmaI-PFGE pattern. The foodborne disease outbreak was considered to be due to contamination in the preparation process of the cake consumed at the feast, which was related to inadequate hygienic conditions, lack of refrigeration and cold chain disruption.

[Foodborne disease outbreak in El Huecú community, province of Neuquén]. / Brote de enfermedad alimentaria en la localidad de El Huecú, provincia de Neuquén.

In the summer of 2006, an epidemic outbreak of acute gastrointestinal illness related to food consumption occurred in a small town in the province of Neuquén, Argentina. During a popular feast, approximately 800 local residents attended lunch held in the facilities of the Municipal Gymnasium. About three hours later, nearly 150 attendees sought medical assistance at the local hospital due to acute gastroenteritis. A case-control epidemiological investigation was conducted using representative non-probability sampling. The epidemiological investigation showed a common-source foodborne disease outbreak with a case-control ratio of 1:1.8. The main symptoms were abdominal cramps (88%), vomiting (73.5%) and diarrhea (60%). The cake was identified as the source of infection (OR 9.79; IC 95%, 2.66-36.00; p = 0.0001), and unsatisfactory hygienic conditions in food production, conservation and handling steps were identified. Coagulase positive, enterotoxigenic Staphylococcus aureus, subspecies aureus was detected in a piece of cake, with a count of 2.4 x 10(6) CFU/g, and in samples from the hands and nostrils of three people involved in food preparation and service. The strains isolated from both the cake and one of the food handlers carried the sea gene, and presented the same Smal-PFGE pattern. The foodborne disease outbreak was considered to be due to contamination in the preparation process of the cake consumed at the feast, which was related to inadequate hygienic conditions, lack of refrigeration and cold chain disruption.

Association between beta2-glycoprotein I gene polymorphisms and pediatric SLE and antiphospholipid antibodies.

Antibodies against phospholipids (PL) and PL-binding proteins have been causally implicated in antiphospholipid syndrome (APS). Mutations in the fifth domain of the beta2-glycoprotein I (beta2GPI) protein, a putative PL-binding site, may play a critical role in APS pathogenesis. The purpose of this study was to identify associations between beta2GPI mutations and both antiphospholipid antibodies (aPL) and their associated clinical manifestations in a pediatric and adolescent cohort and to search for novel mutations. Genetic analysis of beta2GPI was performed in 58 youths with systemic lupus erythematosus (SLE) and/or aPL, to identify known polymorphisms at amino acids 247 and 306 as well as novel mutations in exon 7 of the beta2GPI gene, and their association with aPL-associated clinical manifestations. Our results demonstrate an association between substitution of Val for Leu at AA247 (L247V) of beta2GPI and both the development of aPL (P = 0.05) and aPL-associated clinical manifestations (P = 0.03) among pediatric patients. The odds ratio associated with risk of aPL-associated clinical manifestations for the homozygous VV polymorphism was 5.5 (CI 1.3-23, P = 0.03) for the overall cohort, and 4.75 (CI 0.66-55.49, P = 0.06) after adjusting for ethnicity. The association was not significant after stratifying for SLE versus non-SLE. Association between the VV genotype at amino acid 247 of beta2GPI and clinical disease supports a genetic cause for APS among children and adolescents. Neither novel exon 7 beta2GPI mutations or the previously described C306G polymorphism was identified in this pediatric cohort.

Regulation of human villous trophoblast by insulin-like growth factors and insulin-like growth factor-binding protein-1.

Many studies have implicated the insulin-like growth factors (IGFs) and insulin-like growth factor-binding protein-1 (IGFBP-1) in the control of the feto-maternal interface of human pregnancy, but many of the data are from cell lines derived from primary trophoblast or from extravillous trophoblast. We have obtained highly enriched villous cytotrophoblast (VCT) from first trimester and term human placentae, and investigated the effects of IGF-I, IGF-II and phosphoisoforms of IGFBP-1. First trimester villous trophoblast cells were regulated by all these factors. IGF-II increased cell numbers 3.5-fold after 96 h in culture, and IGF-I had less effect (1.5-fold increase) (both P<0.05). IGF-II also had a greater effect on the levels of matrix metalloproteinase (MMP)-2 and MMP-9. Phosphorylated and non-phosphorylated iso-forms of IGFBP-1 added alone increased cell numbers and MMP levels (P<0.05). IGFBP-1 did not modify the effects of IGF-II on cell numbers or on MMP production. Term VCT numbers and MMP production in vitro were unaffected by IGFs (P>0.05). Cell numbers were increased only by 100 nM IGFBP-1 isoforms (P<0.05), whereas MMP levels released from term cells were optimally increased by 1-10 nM IGFBP-1. Overall, our data show that IGFs regulate only first trimester, but not term, VCT. IGFBP-1 regulates VCT from both gestations, but the effects are concentration and end-point specific. In particular, first trimester cell numbers are more affected by low levels of IGFBP-1, whereas high levels of IGFBP-1 are needed to increase MMP and the converse applies to term VCT; low levels of IGFBP-1 have more effect on MMP levels.

What patients want to know before they have cataract surgery.

AIMS: To investigate what patients want to know before undergoing cataract surgery. METHODS: A written questionnaire was answered by 190 patients prior to cataract surgery. RESULTS: The five pieces of preoperative information rated most important were: chance of visual improvement; when vision would improve; overall risk of losing vision from the operation; effect of not having the operation, and the types of serious complications. When asked "should you be warned of a serious complication if it has a risk of happening", 93.5% said yes to a risk of 1 in 50 and 62.4% to 1 in 1000. Written information was requested by 85.7%. There were few differences between the sexes, and between those having their first or second operation. CONCLUSIONS: Patients most wanted to know benefits and risks, even very small risks. Written information should be provided to ensure coverage and reinforce verbal information.

A fast system for reporting the Farnsworth-Munsell 100-hue colour vision test.

We have developed a system for rapidly reporting the Farnsworth-Munsell (FM) 100-hue test using a personal computer and a bar code scanner. The computer generated report duplicates the conventional manual report of the FM 100-hue test so is very familiar to ophthalmologists and optometrists. The new system has proved to be of great assistance both in saving time and in eliminating arithmetic errors in the scoring calculations. The scanner technique produces two reports, one for each eye, within 4 min of the patient completing the test. This compares with the 60 min required by the conventional manual reporting system. In addition, it also gives a statistical analysis of the results in accordance with Verriest norms. The program is very versatile and user friendly, achieving a standard not present in the other FM 100-hue computerised systems currently available. As a consequence it makes this valuable diagnostic test much more accessible to patients and clinicians.

A comparison of two patient-friendly ERG electrodes.

The ideal electroretinography (ERG) electrode does not exist. In deciding which electrode should be used in clinical practice the capacity to provide reproducible waveforms, maximal amplitudes and minimal irritation to the patient's eyes are the most important characteristics. This study tested two patient friendly electrodes, the gold foil (CH Electrodes, UK) and the H-K loop (Avanta, Slovenia). Seventeen normal volunteers were subjected to three standard measurements namely flash ERGs under photopic and scotopic conditions and the transient pattern ERG (PERG). Each test followed the guidelines set by the International Society for Clinical Electrophysiology of Vision (ISCEV). It was found that the mean values of the flash ERG a and b wave amplitudes and the PERG P50 and N95 amplitudes from the gold foil electrodes were approximately a factor of two larger than those from the H-K loop. In addition most of the subjects (13/17) felt less discomfort with the gold foil electrodes. We reached the conclusion that gold foil electrodes are the electrode of choice because they provide good patient comfort, reasonably high amplitudes and relatively reproducible results.

The regulation of arachidonic acid metabolism in human first trimester trophoblast by cyclic AMP.

Human trophoblast cells are known to release a range of arachidonic acid metabolites into culture medium, including cyclo-oxygenase, lipoxygenase and epoxygenase products. In this study we investigated the effects of dibutyryl cyclic AMP (db cAMP) on arachidonic acid metabolism in human first trimester trophoblast cells, and also determined the distribution of metabolites between intracellular and extracellular compartments. db cAMP increased intracellular levels of radioactivity within 2 min, and extracellular levels of radioactivity were increased after 30 min. These changes were reflected in increased levels of arachidonic acid metabolites in both compartments, indicating that arachidonic acid was metabolised. db cAMP increased intracellular levels of 5,6-epoxyeicosatrienoic acid (5,6-EpETrE) within 2 min of addition to cultured cells. No changes were detected after 5-10 min, but substantial changes were found 30 min after the addition of db cAMP. The dihydroxyeicosatrienoic acid (DiHETrE) breakdown products also increased with similar kinetics. In contrast, levels of 14,15-EpETrE increased after 5-10 min.

The production of progesterone and 5,6-epoxyeicosatrienoic acid by human granulosa cells.

Previous investigations have implicated epoxygenase metabolites of arachidonic acid in the control of steroidogenesis in luteinised granulosa cells. The aim of this study was to assess this hypothesis further. We first determined the responsiveness of the cells in vitro to three different stimuli, namely luteinising hormone (LH), interleukin-1beta (IL-1beta), and dibutyryl cyclic AMP (db. cyclic AMP). Their effects were time-dependent, in that progesterone production from cells incubated for 3 days prior to stimulation responded strongly to db. cyclic AMP, to a lesser extent to LH and not to IL-1beta. After 6 days of preincubation, all three stimuli increased progesterone production, and this preincubation period was used in the remainder of the study.LH and IL-1beta increased the intracellular levels of 5,6-epoxyeicosatrienoic acid (5,6-EpETrE) maximally after 10 min, whereas db. cyclic AMP had a more rapid effect within 2-5 min. There were no changes in levels of 14,15-epoxyeicosatrienoic acid (14,15-EpETrE), indicating that the effect was specific. Levels of dihydroxy derivatives of arachidonic acid were also increased, suggesting rapid metabolism of 5,6-EpETrE to inactive 5,6-DiHETrE. The effects of 5,6-EpETrE on progesterone production were transient, which may be due to the lability of this compound in solution, and limited passage into the granulosa-luteal cell cytoplasm. These results support a role for 5,6-EpETrE in the production of progesterone by human granulosa-luteal cells.

Evaluation of ketorolac (Toradol) with varying amounts of codeine for postoperative extraction pain control.

This study analyzes the combination of oral ketorolac 10 mg with varying amounts of codeine phosphate, and the postoperative pain relief that developed from these combinations. Five groups of patients were administered the codeine/ketorolac combinations. Variations of the combinations were analyzed to ascertain if an optimal analgesic ratio existed. All controllable variables involved with the surgical procedure were held constant to allow for better evaluation of postoperative pain. Results obtained from 67 patients indicated that the best pain relief was achieved with a combination of 10 mg ketorolac and 15 mg codeine phosphate. Codeine alone provided adequate analgesia, but the addition of ketorolac reduced the patients' perceived side effects. The presence of codeine in the analgesic combination was also shown to reduce the number of days that the patient required the medication postoperatively. Reducing the duration of medication use postoperatively may also minimize the possible side effects of ketorolac and codeine, which could develop with extended periods of use.

Ultrastructure of the early human feto-maternal interface co-cultured in vitro.

BACKGROUND: The study was designed to investigate the ultrastructural features of the early human feto-maternal interface when generated by in-vitro co-culture, and compare these with findings reported previously from human pregnancies. METHODS: Placental villi and decidua parietalis tissues from 8-12 week pregnancies were co-cultured in vitro over a 4-day period. The co-incubations were ended at 24 h intervals and processed for electron microscopical studies, and for immunocytochemistry using anti-cytokeratin antibody (CAM 5.2) for trophoblast. RESULTS: Loss of the syncytium at points of contact with the decidual stroma, cytotrophoblast column formation, differentiation and invasion of extravillous trophoblast (EVT) cells into the decidual stroma over the 4-day period of co-culture were observed. Cellular components, such as actin filaments, microtubules, glycogen granules and lamellipodic processes found in EVT cells were consistent with active cellular locomotion. CONCLUSIONS: These ultrastructural studies emphasize the usefulness of this model in investigating the formation of the feto-maternal interface of human pregnancy. The recruitment of cytotrophoblast to the syncytium by a process involving fusion of the intervening plasma membranes, and the migration of EVT cells causing little or no damage to the surrounding decidual cells, resemble in-vivo data.

Predicting the refractive outcome after cataract surgery: the comparison of different IOLs and SRK-II v SRK-T.

AIM: To determine any differences between the predictive abilities of the IOL calculation formulas of SRK-II and SRK-T and to compare these using two different IOL types. METHODS: A prospective, consecutive, single surgeon clinical trial was conducted on 400 consecutive patients who received routine, standardised phacoemulsification cataract surgery. 200 had cataract surgery and had the Alcon MZ30BD, a 5.5 mm one piece PMMA IOL, and another 200 cases used the Chiron C11UB, a silicone plate haptic IOL. The data used optimised A-constants. The measures were preoperative axial length and keratometry, IOL implanted, and refractive error at 4-6 weeks postoperatively. RESULTS: There was no significant difference between the predictive abilities of SRK-II or SRK-T. For the Alcon and Chiron lens respectively, prediction errors using SRK-II were <0.5 dioptres in 58% and 70% and for <1.0 dioptres in 84% and 92%. These differences were statistically significant (chi(2), p=0.02). CONCLUSION: There are differences in the predictability of refractive outcomes between intraocular lens styles.

The effects of a cytokine suppressive anti-inflammatory drug on the output of prostaglandin E(2) and interleukin-1 beta from human fetal membranes.

Fetal membranes are a primary source of prostaglandins and pro-inflammatory cytokines implicated in human parturition, so the inhibition of inflammatory pathways may be of benefit in pregnancies complicated by premature labour. We have therefore investigated the effects of a cytokine-suppressant anti-inflammatory drug (CSAID) on the output of prostaglandin E(2) (PGE(2)) and interleukin (IL)-1 beta from human fetal membranes in vitro. Bacterial endotoxin increased the expression of mRNA for IL-1 beta and type-2 cyclo-oxygenase (COX-2), and there were corresponding increases in the output of IL-1 beta protein and PGE(2). The CSAID decreased IL-1 beta protein, COX-2 expression and PGE(2) output, but not mRNA for IL-1 beta, indicating a post-translational effect on the production of IL-1 beta and a transcriptional affect on COX-2, with an overall reduction in PGE(2). These findings are consistent with the effects of CSAIDs in other systems, and indicate that they are of possible use in premature labour.

PTPRC (CD45) is not associated with the development of multiple sclerosis in U.S. patients.

A C-->G nucleotide transition in exon 4 of PTPRC (encoding protein-tyrosine phosphatase receptor-type C, also known as CD45) was recently reported to be genetically associated with the development of multiple sclerosis (MS). We performed an extensive evaluation of this polymorphism using large family-based and case-control comparisons. Overall, we observed no evidence of genetic association between the PTPRC polymorphism and MS susceptibility or disease course.