Temporally Associated Research Articles

Aplysia giganteatoxicosis in 72 dogs in Western Australia

This study aimed to: (1) confirm a temporal association between exposure to the sea hare Aplysia gigantea and the development of a neurotoxicosis in dogs and (2) further characterise the clinical signs, treatment and outcomes in dogs with this suspected toxicosis. The medical records from four veterinary practices within the Geraldton region of Western Australia were searched for dogs that had been exposed to A. gigantea and subsequently presented to a veterinarian during the period of January 2001 to March 2011. Signalment, exposure history, clinical signs, treatment and outcome were recorded. In total, 72 dogs met the inclusion criteria. Clinical signs included ptyalism, emesis, ataxia, hyperaesthesia, tremors, muscle fasciculations, seizures, nystagmus and respiratory distress; 30 dogs did not have abnormal clinical signs at presentation; 69 dogs were presented during January to April. Treatment included gastrointestinal and dermal decontamination, and supportive management of seizures, tremors and muscle fasciculations. Of the 72 dogs, 65 survived to discharge, 4 died and 3 were euthanased. Information from subsequent examinations was available for 57 dogs and no long-term complications were reported. Exposure to A. gigantea was temporally associated with the development of neuroexcitatory clinical signs in dogs. Gastrointestinal and respiratory signs also occurred in some dogs. Dogs with suspected toxicosis were presented mostly in the months of January to April. The proportion of dogs that died or were euthanased because of worsening clinical signs was approximately 10%.

Seasonality of acute otitis media and the role of respiratory viral activity in children.

Acute otitis media (AOM) occurs as a complication of viral upper respiratory tract infections in young children. AOM and respiratory viruses both display seasonal variation. Our objective was to examine the temporal association between circulating respiratory viruses and the occurrence of pediatric ambulatory care visits for AOM. This retrospective study included 9 seasons of respiratory viral activity (2002 to 2010) in Utah. We used Intermountain Healthcare electronic medical records to assess community respiratory viral activity via laboratory-based active surveillance and to identify children <18 years with outpatient visits and International Classification of Diseases, Ninth Revision codes for AOM. We assessed the strength of the association between AOM and individual respiratory viruses using interrupted time series analyses. During the study period, 96,418 respiratory viral tests were performed; 46,460 (48%) were positive. The most commonly identified viruses were respiratory syncytial virus (22%), rhinovirus (8%), influenza (8%), parainfluenza (4%), human metapneumovirus (3%) and adenovirus (3%). AOM was diagnosed during 271,268 ambulatory visits. There were significant associations between peak activity of respiratory syncytial virus, human metapneumovirus, influenza A and office visits for AOM. Adenovirus, parainfluenza and rhinovirus were not associated with visits for AOM. Seasonal respiratory syncytial virus, human metapneumovirus and influenza activity were temporally associated with increased diagnoses of AOM among children. These findings support the role of individual respiratory viruses in the development AOM. These data also underscore the potential for respiratory viral vaccines to reduce the burden of AOM.

Lipid Resuscitation

Lipid Resuscitation

Hormone concentration changes temporally associated with the hour of transition from preluteolysis to luteolysis in mares

The temporal associations of cortisol, estradiol-17β, and oxytocin with pulses of PGFM at the common hour of transition between preluteolysis and luteolysis was studied in plasma from hourly blood samples in mares ( n = 8). The transitional hour was determined from progesterone concentrations and occurred between 2 PM and 2 AM in all mares. Pulses of PGFM were grouped into those occurring at the last pulse of preluteolysis (preluteolytic pulse), at the hour of transition (transitional), and during luteolysis (luteolytic). The preluteolytic PGFM pulse (45 ± 16 pg/ml at peak) and transitional pulse (42 ± 7 pg/ml) are reportedly less prominent than the first luteolytic pulse (193 ± 36 pg/ml). Cortisol increased ( P < 0.05) between −1 h and 0 h (peak) and then decreased ( P < 0.05) within the hours of the luteolytic PGFM pulse but did not change within the preluteolytic and transitional pulses. Estradiol increased ( P < 0.006) during −3 to 2 h of the luteolytic pulse but not for the other pulses. Oxytocin differed for the hours of the transitional PGFM pulse ( P < 0.02) and the luteolytic pulse ( P < 0.03) but did not differ significantly during the hours of the last preluteolytic pulse. Oxytocin increased ( P < 0.05) between −3 h and 0 h and then decreased ( P < 0.05) within each of the transitional and the luteolytic pulses. The oxytocin results are novel and support the hypothesis that on a temporal basis oxytocin in association with PGF2α accounts for the transition between preluteolysis and luteolysis within a single hour in mares, despite the small transitional PGFM pulse.

Exploring the Temporal Association between Young People's Alcohol Consumption Patterns and Violent Behavior

Alcohol consumption patterns such as binge drinking have routinely been associated with interpersonal assault amongst young people. Examining how drinking patterns are temporally associated with violent behavior during adolescence and young adulthood further develops an understanding of this relationship. This study employs data from the Offending Crime and Justice Survey in England and Wales, offering insight into young people's drinking and offending behavior. A cross-sectional model examines the extent to which binge drinking is associated with the likelihood of committing assault in the same year. An earlier measure of binge drinking (in the previous year) was subsequently used to examine the influence on later violent behavior. Evidence that the pattern of drinking is associated with violent offending, as well as a contemporaneous association between binge drinking and violence in the same year, supports the existing literature in the field and suggests that frequent acute intoxication is a temporally proximal risk factor for the increased propensity of committing interpersonal assault offenses. However, there is no evidence found in the current study to suggest that earlier measures of binge drinking frequency are associated with increased propensity for later violent offending. Furthermore, current findings do not suggest that the association between binge drinking and the propensity for violence is moderated by gender, thus suggesting interventions aimed at reducing violent offending ought to address binge drinking in both males and females.

The role of lower extremity joint powers in successful stair ambulation

Ascending stairs is an important functional activity that is affected by lower extremity pathology including amputation. Although several studies have demonstrated stair ascent is more challenging than level ground walking, our understanding of the mechanics remains limited. The purpose of this study was to determine the association between lower extremity joint power generation and vertical COM acceleration (COMA) during stair ascent. Twenty-two healthy individuals underwent a biomechanical gait assessment while walking up a 16-step instrumented staircase. The association between the peak joint powers and peak COMA during stance were assessed with respect to timing and magnitude. With respect to timing, peak ankle joint power was highly correlated with peak COMA (R2=0.93), while peak knee and hip joint powers demonstrated limited association with COMA (R2=0.41 and 0.08, respectively). Only the magnitude of peak ankle power was associated with peak COMA (R2=0.3).Significant temporal and magnitude associations between peak ankle joint power and peak COMA suggest ankle power is a key contributor to COMA. Although peak knee joint power and COMA are temporally associated, the association is weaker and the occurrence of peak joint knee power is nearly 10% after peak COMA, suggesting knee joint power plays a lesser role in COMA. These combined findings indicate the role of trail limb ankle plantarflexors should be recognized in the stair ascent cycle definition and demonstrate the potential importance of a power generated by the ankle plantarflexors to normalize stair ascent performance following lower extremity amputation.

The temporal association of sphenoid sinus mucosal thickening on MR imaging with pituitary apoplexy

Pituitary apoplexy is an infrequent but potentially devastating complication in patients with pituitary adenomas. Previous studies have cited an association between MR visualized sphenoid sinus mucosal thickening and apoplexy. However, uncertainties still remain on the significance and temporal association of this finding with pituitary apoplexy. We provide a clinical study that better delineates this temporal association and also provides histopathologic data for sinus thickening compared to control subjects. We report on two patients who received serial MR scans leading to the diagnosis of pituitary apoplexy. Patient 1 demonstrated new sphenoid sinus mucosal thickening with the onset of apoplexy. Patient 2 had progressive thickening of sphenoid sinus mucosa from presentation to repeat scanning demonstrating apoplexy. Both patients underwent transsphenoidal resection of their pituitary adenomas with pathology demonstrating inflamed sphenoid sinus mucosa. Sphenoid sinus mucosal thickening, as demonstrated on MRI, is temporally associated with pituitary apoplexy, likely as an acute and precedent finding.

Streptococcal Upper Respiratory Tract Infections and Exacerbations of Tic and Obsessive-Compulsive Symptoms: A Prospective Longitudinal Study

The objective of this blinded, prospective, longitudinal study was to determine whether new group A β hemolytic streptococcal (GABHS) infections are temporally associated with exacerbations of tic or obsessive-compulsive (OC) symptoms in children who met published criteria for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). A group of children with Tourette syndrome and/or OC disorder without a PANDAS history served as the comparison (non-PANDAS) group. Consecutive clinical ratings of tic and OC symptom severity were obtained for 31 PANDAS subjects and 53 non-PANDAS subjects. Clinical symptoms and laboratory values (throat cultures and streptococcal antibody titers) were evaluated at regular intervals during a 25-month period. Additional testing occurred at the time of any tic or OC symptom exacerbation. New GABHS infections were established by throat swab cultures and/or recent significant rise in streptococcal antibodies. Laboratory personnel were blinded to case or control status, clinical (exacerbation or not) condition, and clinical evaluators were blinded to the laboratory results. No group differences were observed in the number of clinical exacerbations or the number of newly diagnosed GABHS infections. On only six occasions of a total of 51 (12%), a newly diagnosed GABHS infection was followed, within 2 months, by an exacerbation of tic and/or OC symptoms. In every instance, this association occurred in the non-PANDAS group. This study provides no evidence for a temporal association between GABHS infections and tic/OC symptom exacerbations in children who meet the published PANDAS diagnostic criteria.

Temporal Associations Between Thoracic Volume Overload and Malignant Ventricular Arrhythmias: A Study of Intrathoracic Impedance

Acute exacerbations of heart failure (HF) are believed to trigger malignant ventricular arrhythmias, but the temporal association between fluid accumulation and ventricular arrhythmias has not been evaluated in an objective manner. We hypothesized that increased intrathoracic fluid accumulation in patients with HF, as measured by an index of intrathoracic impedance, is associated with an increased risk of ventricular arrhythmias. We analyzed interrogations in a cohort of 96 patients with left ventricular dysfunction (EF ≤ 35%) with devices that monitor intrathoracic impedance (OptiVol fluid index). Treated episodes of ventricular tachycardia or fibrillation (VT/VF) were adjudicated and stratified according to predetermined fluid index thresholds (OptiVol indices of 15, 30, 45, 60 Ω-days). VT/VF episodes occurred in 16 patients (17%). VT/VF was more common on days when the fluid index was elevated using threshold values of 15, 30, and 45 Ω-days (P = 0.006, 0.04, 0.02, respectively). There were no differences in the percent of time above any threshold between patients with and without VT/VF. In patients with HF who develop VT/VF, volume overload, as detected by an index incorporating changes in intrathoracic impedance, was temporally associated with malignant ventricular tachyarrhythmias.

Socioeconomic associations of improved maternal, neonatal, and perinatal survival in Qatar

This retrospective study analyzed the temporal association between socioeconomic development indices and improved maternal, neonatal, and perinatal survival in the State of Qatar over a period of 35 years (1974–2008). We explored the association between reduction in poverty, improvement in maternal education, and perinatal health care on the one hand, and increased maternal, neonatal, and perinatal survival on the other hand. Yearly mortality data was ascertained from the perinatal and neonatal mortality registers of the Women’s Hospital and the national database in the Department of Preventive Medicine at Hamad Medical Corporation in Doha. A total of 323,014 births were recorded during the study period. During these 35 years, there was a remarkable decline (P < 0.001) in Qatar’s neonatal mortality rate from 26.27/1000 in 1974 to 4.4/1000 in 2008 and in the perinatal mortality rate from 44.4/1000 in 1974 to 10.58/1000 in 2008. Qatar’s maternal mortality rate remained zero during 1993, 1995, and then in 1998–2000. The maternal mortality rate was 11.6/100,000 in 2008. For the rest of the years it has been approximately 10/100,000. Across the study period, the reduction in poverty, increase in maternal education, and improved perinatal health care were temporally associated with a significant improvement in maternal, neonatal, and perinatal survival. The total annual births increased five-fold during the study period, with no negative impact on survival rates. Neonatal mortality rates in Qatar have reached a plateau since 2005. We also conducted a substudy to assess the association between improvements in survival rates in relation to health care investment. For this purpose, we divided the study period into two eras, ie, era A (1974–1993) during which major health care investment was in community-based, low-cost interventions, and era B (1994–2008) during which the major health care investment was in high-technology institutional interventions. Although from 1974–1993 (era A) the per capita health expenditure increased by only 19% as compared with a 137% increase in 1994–2008 (era B). The decline in neonatal and perinatal mortality rates was three times steeper during era A than in era B. The decline in neonatal and perinatal mortality rates was also significant (P < 0.001) when analyzed separately for era A and era B. We concluded that across the 35-year period covered by our study, the reduction in poverty, increased maternal education, and improved perinatal health care were temporally associated with improved maternal, neonatal, and perinatal survival in the State of Qatar. From the subanalysis of era A and era B, we concluded that low-cost, community-based interventions, on the background of socioeconomic development, have a stronger impact on maternal, neonatal, and perinatal survival as compared with high-cost institutional interventions.

Temporal association of elevations in serum cardiac troponin T and myocardial oxidative stress after prolonged exercise in rats

The objective of this study was to determine if prolonged exercise resulted in the appearance of cardiac troponin T (cTnT) in serum and whether this was associated with elevated levels of myocardial oxidative stress. Forty-five male Sprague-Dawley rats were randomized into four groups and killed before (PRE-EX), immediately (0HR), 2 (2HR) and 24h (24HR) after a 3-h bout of swimming with 5% body weight attached to their tail. In all animals serum cTnT was assayed using 3rd generation electrochemiluminescence. In homogenized heart tissue myocardial malondialdehyde (MDA), a marker of lipid peroxidation, glutathione (GSH), and a non-enzymatic estimate of total antioxidant capacity (T-AOC) were assessed spectrophotometrically. At PRE-EX cTnT was undetectable in all animals. At 0HR (median, range: 0.055, 0.020-0.100) and 2HR post-exercise (0.036, 0.016-2.110) cTnT was detectable in all animals (P<0.05). At 24HR post-exercise cTnT was undetectable in all animals. An elevation in MDA was observed 0HR (mean±SD: 1.7±0.2nmolmgpro(-1)) and 2HR (1.6±0.3nmolmgpro(-1)) post-exercise compared with PRE-EX (1.3±0.2nmolmgpro(-1); P<0.05). The antioxidant response to this challenge was a significant (P<0.05) decrease in GSH 2HR and 24HR post-exercise. Despite this T-AOC did not alter across the trial (P>0.05). The results indicated that prolonged and strenuous exercise in rats resulted in an elevation in cTnT, a biomarker of cardiomyocyte damage, in all animals 0HR and 2HR after exercise completion. The time course of cTnT elevation was temporally associated with evidence of increased lipid peroxidation in the rat heart.

Erythropoietin-Associated CFU-E Expansion: A Novel Mechanism Responsible for Erythroid Recovery Following Sublethal Radiation.

Abstract 1483Poster Board I-506Although the synthesis of two million red blood cells every second is essential for the maintenance of steady state levels of blood cells as well as our well-being, very little is known about the sensitivity of the erythroid lineage to injury or its kinetics and mechanisms of recovery. A novel multispectral imaging flow cytometry analysis utilizing the AMNIS ImageStream and functional colony assays were utilized to study the response of the erythroid lineage in C57Bl/6 mice following 4 Gray whole body irradiation. BrdU cell cycle analysis and erythropoietin ELISA assays were also utilized to investigate erythroid recovery after radiation injury. Two days post-radiation, all erythroid progenitors and precursors in the marrow were severely depleted. Over the next week, early-stage progenitors (BFU-E) only made a partial recovery. In marked contrast, late-stage progenitors (CFU-E) dramatically expanded in numbers at 5-6 days post-radiation to greater than 200% of normal. These CFU-E subsequently generated a wave of erythroid precursors that culminated in the emergence of circulating reticulocytes beginning at 8-9 days post-radiation. Rapid expansion of the CFU-E compartment was associated with an increase in cell cycling. CFU-E expansion was also temporally associated with an acute 20-fold increase in circulating levels of erythropoietin (EPO). Additionally, exogenous EPO administration at 4 days post-radiation resulted in further expansion of CFU-E 2 days later. Interestingly, erythroid progenitors and precursors were not found in the spleen after radiation, indicating that recovery of the erythroid lineage after direct marrow injury is not associated with extramedullary erythropoiesis. We conclude that erythroid progenitors and precursors, unlike circulating erythrocytes, are exquisitely sensitive to clastogenic insults such as radiation. Furthermore, we conclude that the acute recovery of erythropoiesis following sublethal radiation injury is centered on profound expansion and robust cycling of CFU-E. The temporal association of this CFU-E expansion both with the endogenous upregulation and with the exogenous administration of EPO suggests that CFU-E expansion is due primarily to erythropoietin stimulation. We hypothesize CFU-E expansion in the marrow may represent a novel adaptive mechanism of the erythroid lineage to acute injury. Overall, a more thorough understanding of radiation-induced erythroid injury and recovery will ultimately lead to new treatments to protect and mitigate the hematopoietic system from clastogenic agents such as radiation and chemotherapy. Disclosures:No relevant conflicts of interest to declare.

Evolutionary Patterns of Eastern Equine Encephalitis Virus in North versus South America Suggest Ecological Differences and Taxonomic Revision

The eastern equine encephalitis (EEE) complex consists of four distinct genetic lineages: one that circulates in North America (NA EEEV) and the Caribbean and three that circulate in Central and South America (SA EEEV). Differences in their geographic, pathogenic, and epidemiologic profiles prompted evaluation of their genetic diversity and evolutionary histories. The structural polyprotein open reading frames of all available SA EEEV and recent NA EEEV isolates were sequenced and used in evolutionary and phylogenetic analyses. The nucleotide substitution rate per year for SA EEEV (1.2 x 10(-4)) was lower and more consistent than that for NA EEEV (2.7 x 10(-4)), which exhibited considerable rate variation among constituent clades. Estimates of time since divergence varied widely depending upon the sequences used, with NA and SA EEEV diverging ca. 922 to 4,856 years ago and the two main SA EEEV lineages diverging ca. 577 to 2,927 years ago. The single, monophyletic NA EEEV lineage exhibited mainly temporally associated relationships and was highly conserved throughout its geographic range. In contrast, SA EEEV comprised three divergent lineages, two consisting of highly conserved geographic groupings that completely lacked temporal associations. A phylogenetic comparison of SA EEEV and Venezuelan equine encephalitis viruses (VEEV) demonstrated similar genetic and evolutionary patterns, consistent with the well-documented use of mammalian reservoir hosts by VEEV. Our results emphasize the evolutionary and genetic divergences between members of the NA and SA EEEV lineages, consistent with major differences in pathogenicity and ecology, and propose that NA and SA EEEV be reclassified as distinct species in the EEE complex.

Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines

Because of the advent of a new influenza A H1N1 strain, many countries have begun mass immunisation programmes. Awareness of the background rates of possible adverse events will be a crucial part of assessment of possible vaccine safety concerns and will help to separate legitimate safety concerns from events that are temporally associated with but not caused by vaccination. We identified background rates of selected medical events for several countries. Rates of disease events varied by age, sex, method of ascertainment, and geography. Highly visible health conditions, such as Guillain-Barré syndrome, spontaneous abortion, or even death, will occur in coincident temporal association with novel influenza vaccination. On the basis of the reviewed data, if a cohort of 10 million individuals was vaccinated in the UK, 21.5 cases of Guillain-Barré syndrome and 5.75 cases of sudden death would be expected to occur within 6 weeks of vaccination as coincident background cases. In female vaccinees in the USA, 86.3 cases of optic neuritis per 10 million population would be expected within 6 weeks of vaccination. 397 per 1 million vaccinated pregnant women would be predicted to have a spontaneous abortion within 1 day of vaccination.

Temporal association of large granular lymphocytosis, neutropenia, proviral load, and FasL mRNA in cats with acute feline immunodeficiency virus infection

During acute feline immunodeficiency virus-C PGammar (FIV-C-PG) infection, we observed that cats develop large granular lymphocyte (LGL) lymphocytosis concurrent with a marked neutropenia that is temporally associated with the rise and fall of FIV-C-PG proviral loads. LGLs, generally considered to be analogous to natural killer (NK) cells, can also be highly cytolytic CD8/CD57 T cells. Neutropenia has been reported during acute human immunodeficiency virus (HIV-1) infection, but there is a paucity of information describing the pathogenesis of this condition. During HIV-1 infection, LGLs have been shown to be both CD16 + NK cells and CD8 +/CD57 + T cells, but an association with neutropenia has not been described. However, neutropenia with concurrent LGL lymphocytosis has been demonstrated in both LGL leukemia and common variable immunodeficiency syndrome in people, and in both syndromes, an increase in soluble Fas ligand (FasL) has been associated with neutrophil apoptosis leading to neutropenia. Flow cytometric analysis demonstrated increases in CD56 and CD8 peripheral blood cell surface expression during acute FIV-C-PG infection. Expression of FasL mRNA was increased at the same time points as these peripheral hematologic abnormalities, and also decreased as FIV-C-PG proviral load reached set point. We describe an interesting temporal association between innate immune responses and viral load during acute FIV-C-PG infection, which has similarities to HIV-1 infection and other immune dyscrasias of people, and which may contribute to the neutropenia and LGL lymphocytosis during FIV-C-PG infection.

Cerebral angioedema associated with enalapril

Cerebral angioedema associated with enalapril

Disruption of the periovulatory LH surge by a transient increase in circulating 17β-estradiol at the time of ovulation in mares

The mechanism for a reported temporal association between ovulation and a transient disruption in the periovulatory increase in LH concentrations was studied in nine mares treated with human chorionic gonadotropin when the preovulatory follicle was ≥32 mm. Examinations for ovulation detection and blood collection were done at 2-h intervals and the results were retrospectively centralized to ovulation (Hour 0). Concentrations of LH began to increase ( P < 0.03) rapidly at Hour −18, decreased ( P < 0.04) between Hours 0 and 6, and again increased ( P < 0.0001) after Hour 12. A progressive decrease ( P < 0.0001) in estradiol between Hours −30 and 24 was interrupted temporarily by an increase ( P < 0.01) between Hours −2 and 0 and a decrease ( P < 0.007) between Hours 0 and 2. Results indicated that a disruption and depression in the periovulatory LH surge occurred at the time of detected ovulation in mares and was temporally associated with a transient increase in estradiol during an overall progressive decline. The disruption in LH concentrations is attributable to the estradiol increase, based on a reported negative effect of estradiol on LH. The source of the circulating estradiol was likely from the discharge of estradiol-laden follicular fluid into the abdomen during ovulation and rapid absorption of estradiol into the circulation.

Mild Head Trauma and Chronic Headaches in Returning US Soldiers

To determine the incidence and types of head or neck trauma and headache characteristics among US Army soldiers evaluated for chronic headaches at a military neurology clinic following a combat tour in Iraq. Head or neck trauma and headaches are common in US soldiers deployed to Iraq. The temporal association between mild head trauma and headaches, as well as the clinical characteristics of headaches associated with mild head trauma, has not been systematically studied in US soldiers returning from Iraq. A retrospective cohort study was conducted with 81 US Army soldiers from the same brigade who were evaluated at a single military neurology clinic for recurrent headaches after a 1-year combat tour in Iraq. All subjects underwent a standardized interview and evaluation to determine the occurrence of head or neck trauma during deployment, mechanism and type of trauma, headache type, and headache characteristics. In total, 33 of 81 (41%) soldiers evaluated for headaches reported a history of head or neck trauma while deployed to Iraq. A total of 18 (22%) subjects had concussion without loss of consciousness and 15 (19%) had concussion with loss of consciousness. Ten subjects also had an accompanying traumatic neck injury. No subjects had moderate or severe traumatic brain injury. Exposure to blasts was the most common cause of trauma, accounting for 67% of head and neck injuries. Headaches began within one week after trauma in 12 of 33 (36%) soldiers with head or neck injury. Another 12 (36%) reported worsening of pre-existing headaches after trauma. Headaches were classified as migraine type in 78% of soldiers with head or neck trauma. Headache types, frequency, severity, duration, and disability were similar for soldiers with and without a history of head or neck trauma. A history of mild head trauma, usually caused by exposure to blasts, is found in almost half of returning US combat troops who receive specialized care for headaches. In many cases, head trauma was temporally associated with either the onset of headaches or the worsening of pre-existing headaches, implicating trauma as a precipitating or exacerbating factor, respectively. Headaches in head trauma-exposed soldiers are usually migraine type and are similar to nontraumatic headaches encountered at a military specialty clinic.

Self‐limited febrile syndromes temporally associated with the use of propofol for sedation in gastrointestinal endoscopic procedures

To investigate cases of febrile illnesses in patients who received propofol for sedation during gastrointestinal endoscopy. Active case finding for patients who underwent endoscopy between 1 April and 30 May 2007 and suffered unexplained fever, chills, or myalgia within 48 hour after the procedure. We reviewed medications and clinical practices to find factors associated with the reactions. Seventy-four cases at eight facilities in five states were identified yielding a rate of 36 reactions per 1000 procedures, compared with a baseline rate of 0.6 per 1000. The majority of patients experienced self-limited fever (89.2%), chills (73.0%), or myalgia (63.5%). Blood samples from five patients were collected for culture; no organisms grew. All health care facilities that reported cases and fully participated in the investigation (n = 7) had received a common lot of propofol just before recognition of the first case. Bacterial endotoxin and sterility testing on unopened vials from this lot of propofol showed no abnormalities. Cases terminated after facilities stopped using the associated lot of propofol. We found a temporal association between a particular lot of propofol and an outbreak of febrile illnesses at several healthcare facilities performing endoscopy. When propofol is used to sedate patients for endoscopy, fever is a rare outcome and healthcare professionals should investigate clusters of these reactions. Post-procedure surveillance is important to identify possible medication reactions.

Ultrastructural and temporal changes of the microvascular basement membrane and astrocyte interface following focal cerebral ischemia

Microvascular integrity is lost during cerebral ischemia. Detachment of the microvascular basement membrane (BM) from the astrocyte, as well as degradation of the BM, is responsible for the loss of microvascular integrity. However, their ultrastructural and temporal changes during cerebral ischemia are not well known. Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO) for 1, 4, 8, 12, 16, 20, and 48 hr. By using transmission electron microscopy, the proportion of intact BM-astrocyte contacts and electron densities of the BM were measured from five randomly selected microvessels in the ischemic basal ganglia. Their temporal changes and associations with activities of the matrix metalloproteinases (MMPs) were investigated. The intact portion of the BM-astrocyte contacts was decreased significantly within 4 hr and was rarely observed at 48 hr after MCAO. Decreases in the electron density and degradation of the BM were significant 12 hr after MCAO. The intact BM-astrocyte contacts and the mean BM density showed a significant positive correlation (r = 0.784, P < 0.001). MMP-9 activity was correlated negatively with the intact BM-astrocyte contacts (r = -0.711, P < 0.001) and with the BM density (r = -0.538, P = 0.0016). The increase in MMP-9 coincided temporally with the loss of the BM-astrocyte contacts and a decrease in the BM density. Ultrastructural alterations occurring in the microvascular BM and its contacts with astrocyte endfeet were temporally associated in cerebral ischemia. Time courses of their alterations should be considered in the treatment targeted to the microvascular BM and its contact with astrocytes.