Immunologic Difference between Hypersensitivity to Mosquito Bite and Hemophagocytic Lymphohistiocytosis Associated with Epstein-Barr Virus Infection

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, virus-triggered immune disease. Hypersensitivity to mosquito bite (HMB), a presentation of Chronic Active Epstein-Barr Virus infection (CAEBV), may progress to HLH. This study aimed to investigate the immunologic difference between the HMB episodes and the HLH episodes associated with EBV infection. Immunologic changes of immunoglobulins, lymphocyte subsets, cytotoxicity, intracellular perforin and granzyme expressions, EBV virus load and known candidate genes for hereditary HLH were evaluated and compared. In 12 HLH episodes (12 patients) and 14 HMB episodes (4 patients), there were both decreased percentages of CD4+ and CD8+ and increased memory CD4+ and activated (CD2+HLADR+) lymphocytes. In contrast to HMB episodes that had higher IgE levels and EBV virus load predominantly in NK cells, those HLH episodes with virus load predominantly in CD3+ lymphocyte had decreased perforin expression and cytotoxicity that were recovered in the convalescence period. However, there was neither significant difference of total virus load in these episodes nor candidate genetic mutations responsible for hereditary HLH. In conclusion, decreased perforin expression in the HLH episodes with predominant-CD3+ EBV virus load is distinct from those HMB episodes with predominant-NK EBV virus load. Whether the presence of non-elevated memory CD4+ cells or activated lymphocytes (CD2+HLADR+) increases the mortality rate in the HLH episodes remains to be further warranted through larger-scale studies.     

Dronedarone for Recurrent Ventricular Tachycardia: A Real Alternative?

Sustained ventricular tachycardia (VT) is an important cause of morbidity and sudden death in patients with dilated cardiomyopathy. Although ICD effectively terminate VT episodes and improve survival, shocks reduce quality of life, and episodes of VT predict increased risk of heart failure and death despite effective therapy. Patients suffering recurrent VT episodes remain a challenge. Antiarrhytmic therapy reduces VT episodes, but it is associated with serious adverse events, and disappointing efficacy. Catheter ablation has emerged as an important option to control recurrent VT, but major procedure-related complications, and even death, are still issues to concern. And even with these armamentaria, some patients still have recurrent VT episodes and ICD shocks. We report on a patient with non-ischemic dilated cardiomyopathy and recurrent ventricular tachycardia resistant to multiple antiarrhytmic agents, in whom dronedarone was effective in completely suppressing ventricular tachycardia episodes.     

Microbial Translocation Contribute to Febrile Episodes in Adults with Chemotherapy-Induced Neutropenia

In this study we sought to determine the contribution of microbial translocation to febrile episodes with no attributable microbiological cause (Fever of Unknown Origin, FUO) in an adult febrile neutropaenic cohort. Endotoxin concentrations were measured with the chromogenic Limulus Amoebocyte Assay and used as a direct measure of bacterial products whilst soluble CD14 (sCD14), measured with ELISA was selected as an indicator of the early host response to endotoxins. Endotoxin concentrations in this cohort were generally elevated but did not differ with the presentation of fever. Further stratification of the febrile episodes based on the microbiological findings revealed significantly (p = 0.0077) elevated endotoxin concentrations in FUO episodes compared with episodes with documented bacterial and viral findings. sCD14 concentrations were however, elevated in febrile episodes (p = 0.0066) and no association was observed between sCD14 concentration and microbiological findings. However, FUO episodes and episodes with Gram-negative bacteraemia were associated with higher median sCD14 concentrations than episodes with Gram-positive bacteraemia (p = 0.030). In conclusion, our findings suggest that in the absence of microbiological findings, microbial translocation could contribute to febrile episodes in an adult neutropaenic cohort. We further observed an association between prophylactic antibiotic use and increased plasma endotoxin concentrations (p = 0.0212).     

General Practice Observed: Survey of General Practice Records

A study of a sample of records from eight general practices showed that 10% of patients'' ages were not recorded, that 99% of males had no indication of their marital state, and 60% did not have an occupation recorded. In recording of disease episodes a diagnosis was recorded in a little over half of the episodes and was the only recorded item in 10% of records. The recording of the therapeutic agent used was the most frequently recorded item, occurring in 70% of episodes, but the amount prescribed was recorded in only one-quarter of the episodes and the dosage in less than one-fifth. Less than half of the episodes had any symptoms recorded and only one-third had a physical sign recorded.     

COMBINING SELECTIVE EPISODES TO ESTIMATE LIFETIME NONLINEAR SELECTION

Studies measuring natural selection acting via different components of fitness may provide insight into such central questions in evolutionary biology as the evolution of life histories and sexual dimorphism. It is often desirable to combine estimates of selection at different episodes to understand how they interact to produce total lifetime selection. When selective episodes are sequential, total directional selection may be calculated by summing directional selection across episodes. However, it is unclear whether lifetime nonlinear (e.g., stabilizing, disruptive, or correlational) selection may be similarly calculated using estimates of quadratic selection from sequential episodes. Here, I show that lifetime quadratic selection depends not only upon the sum total of quadratic selection across episodes but also upon the pattern of directional selection across episodes. In certain cases, the effects of directional selection across episodes may cancel one another, leading to no net directional selection but strong stabilizing selection. This result suggests that true stabilizing selection may be more common than previously thought, especially when the entire life cycle is considered. The equations derived here are easily applicable to empirical data, as is illustrated both with a simulated dataset and with a reanalysis of a study of quadratic selection in dark‐eyed juncos.     

Circadian Variation of Myocardial Ischemia in Patients with Stable Coronary Artery Disease

The circadian variation of myocardial ischemia detected during 24-h ambulatory electrocardiographic monitoring (AEM) was analyzed in 123 patients with stable angina pectoris, positive exercise test, and angiographically proven coronary artery disease. A total of 437 ischemic episodes (ST-segment depression ≥ 1 mm and duration ≥ 1 min) were observed; 333 (76%) episodes remained asymptomatic, and only 104 (24%) episodes were accompanied by anginal pain. Ischemic episodes predominantly occurred during the morning hours, between 6 a.m. and noon, and another smaller peak was observed in the afternoon, between 4 and 5 p.m.; this diurnal pattern was influenced neither by the extent of coronary artery disease nor the degree of left ventricular dysfunction. The circadian variation was restricted to the 345 (78%) ischemic episodes preceded by increases in heart rate; the 92 (22%) episodes without prior heart rate changes occurred randomly throughout the day. The morning peak in ischemic episodes was not associated with less myocardial oxygen supply; in contrast, heart rate profile showed parallel increases during the morning and afternoon hours, indicating elevated myocardial demand during these periods. Ischemia-related ventricular arrhythmias were concentrated during the morning hours, but their overall prevalence was low–28 (6%) of 437 ischemic episodes. These findings may provide further insight into the pathomechanisms of acute clinical events in patients with coronary artery disease, since the circadian variation of myocardial ischemia is very similar to that observed for the onset of myocardial infarction and sudden cardiac death.     

Circadian Variation of Myocardial Ischemia in Patients with Stable Coronary Artery Disease

The circadian variation of myocardial ischemia detected during 24-h ambulatory electrocardiographic monitoring (AEM) was analyzed in 123 patients with stable angina pectoris, positive exercise test, and angiographically proven coronary artery disease. A total of 437 ischemic episodes (ST-segment depression ≥ 1 mm and duration ≥ 1 min) were observed; 333 (76%) episodes remained asymptomatic, and only 104 (24%) episodes were accompanied by anginal pain. Ischemic episodes predominantly occurred during the morning hours, between 6 a.m. and noon, and another smaller peak was observed in the afternoon, between 4 and 5 p.m.; this diurnal pattern was influenced neither by the extent of coronary artery disease nor the degree of left ventricular dysfunction. The circadian variation was restricted to the 345 (78%) ischemic episodes preceded by increases in heart rate; the 92 (22%) episodes without prior heart rate changes occurred randomly throughout the day. The morning peak in ischemic episodes was not associated with less myocardial oxygen supply; in contrast, heart rate profile showed parallel increases during the morning and afternoon hours, indicating elevated myocardial demand during these periods. Ischemia-related ventricular arrhythmias were concentrated during the morning hours, but their overall prevalence was low-28 (6%) of 437 ischemic episodes. These findings may provide further insight into the pathomechanisms of acute clinical events in patients with coronary artery disease, since the circadian variation of myocardial ischemia is very similar to that observed for the onset of myocardial infarction and sudden cardiac death.     

Effect of hypoxic episode number and severity on ventilatory long-term facilitation in awake rats.

Episodic hypoxia induces a persistent augmentation of respiratory activity, termed long-term facilitation (LTF). Phrenic LTF saturates in anesthetized animals such that additional episodes of stimulation cause no further increase in LTF magnitude. The present study tested the hypothesis that 1) ventilatory LTF also saturates in awake rats and 2) more severe hypoxia and hypoxic episodes increase the effectiveness of eliciting ventilatory LTF. Minute ventilation was measured in awake, male Sprague-Dawley rats by plethysmography. LTF was elicited by five episodes of 10% O(2) poikilocapnic hypoxia (magnitude: 17.3 +/- 2.8% above baseline, between 15 and 45 min posthypoxia, duration: 45 min) but not 12 or 8% O(2). LTF was also elicited by 10, 20, and 72 episodes of 12% O(2) (19.1 +/- 2.2, 18.9 +/- 1.8, and 19.8 +/- 1.6%; 45, 60, and 75 min, respectively) but not by three or five episodes. These results show that there is a certain range of hypoxia that induces ventilatory LTF and that additional hypoxic episodes may increase the duration but not the magnitude of this response.     

Fever in the Neutropenic Patient

A total of 100 consecutive episodes of fever of 101° F (38·3°C) or above in 56 neutropenic patients have been investigated. All the patients had either acute leukaemia or aplastic anaemia. A cause for the fever was found in 68 of these episodes, in 87% of which it was due to infection. The commonest single finding was septicaemia (30 episodes). Only two episodes of fever could be ascribed solely to the underlying malignant disease.Infection should be assumed to be present and the cause of fever in neutropenic patients until proved otherwise.     

Sulfisoxazole Chemoprophylaxis and Recurrent Otitis Media

Sulfisoxazole, 75 mg per kg per day, was administered for 13 weeks to all children with otitis media recurring at a rate of at least once every other month. The first 26 patients began prophylaxis during the months of January and February of 1979. To compare rates of otitis media with those in children not receiving concurrent prophylaxis during the same season, a matched control was randomly chosen as a child who began prophylaxis on the day nearest that when a study patient completed prophylaxis. The rates of otitis media during this same period were determined as the number of episodes per patient-month. Of the 26 treated patients, 11 had 16 episodes of otitis media in 72 patient-months (0.22 episodes per patient-month), in contrast to the 26 untreated patients who had 63 episodes in the same period (0.88 episodes per patient-month). This 75% reduction in incidence was statistically significant by X² analysis (P<.005). The two groups of children were comparable in age, sex, nursery school attendance, family history of allergy and number of episodes in the three months preceding chemoprophylaxis. These findings support the short-term chemoprophylactic use of sulfisoxazole for recurrent otitis media.     

Effects of heart isolation,voltage-sensitive dye,and electromechanical uncoupling agents on ventricular fibrillation

We tested whether the interventions typically required for optical mapping affect activation patterns during ventricular fibrillation (VF). A 21 x 24 unipolar electrode array (1.5 mm spacing) was sutured to the left ventricular epicardium of 16 anesthetized pigs, and four episodes of electrically induced VF (30-s duration) were recorded. The hearts were then rapidly excised and connected to a Langendorff perfusion apparatus. Four of the hearts were controls, in which 24 additional VF episodes were then mapped. In the remaining 12 hearts, four VF episodes were mapped after isolation, four more episodes were mapped after exposure to the voltage-sensitive dye di-4-ANEPPS, and six more episodes were mapped after exposure to the electromechanical uncoupling agents diacetyl monoxime (DAM; 20 mmol/l, n = 6) or cytochalasin D (CytoD; 10 micromol/l, n = 6). VF episodes were separated by 4 min. VF activation patterns were quantified using custom pattern analysis algorithms. From comparisons with time-corrected control data, all interventions significantly changed VF patterns. Most changes were broadly consistent with slowing and regularization due to loss of excitability. Heart isolation had the largest effect on VF patterns, followed by CytoD, DAM, and dye.     

Patterns of bleeding in adolescents with severe haemophilia A.

Eighty-two boys with severe haemophilia A who spent some time at Lord Mayor Treloar College during 1973-7 were studied. All episodes of bleeding that occurred during term time were recorded, along with the number of transfusions. The bleeding frequency among these boys, most of them aged 10-17 years, increased steadily from 8,31 episodes/100 days in 1973 to 12,63 episodes/100 days in 1977. At the same time there was a steady fall in bleeding frequency with age. Altogether 24% of bleeding episodes were into the elbow joint, 22% into the knee, and 15% into the ankle. As the boys grew older the proportion of bleeding episodes in the legs declined and that in the arms increased. The overall results reflect the fact that special schools now see only the severest cases of haemophilia. The pattern of bleeding during adolescence suggests that concepts of management of arm bleeding need modifying.     

Elevated birch pollen episodes in Denmark: contributions from remote sources

The purpose of this study was to investigate the relationship between possible long-distance transport of birch pollen and episodes of elevated concentration in Denmark. By analysis of a twenty-six year (1980–2006) time-series of bi-hourly birch pollen counts from two sites (Copenhagen and Viborg) episodes of elevated counts (more than 100 grains) were identified in fewer than 2% of cases. Trajectory analysis showed that such episodes are primarily associated with long-distance transport from Eastern Europe and Scandinavia (43 and 33% of events, respectively); the lowest contribution originated from the British Isles. Long-term episodes (as in 1993 and 2006) occurred when atmospheric conditions favored long-distance transport from several source regions in succession.     

Late pleistocene paleoclimatology: Planktonic foraminiferal analyses of sediment cores from the central North Atlantic

Planktonic foraminiferal analyses of six deep-sea sediment cores from the central North Atlantic east of the Azores Islands between 37°N and 40°N show distinct oscillations in planktonic foramineferal assemblages during the last 300,000 years. A paleoclimatic curve has been constructed using “Total Fauna Analysis” that reveals three glacial and four interglacial episodes. Relatively minor climatic oscillations are superimposed upon the major glacial-interglacial episodes. The paleoclimatic curve is similar to previous paleoclimatic curves from the Atlantic and adjacent areas. Minor paleoclimatic fluctuations are more distinct in paleoclimatic curves from high latitudes of the Atlantic.The faunal assemblages are transitional between subarctic and subtropical assemblages. During portions of the interglacial episodes, the assemblage is dominated by Globorotalia inflata. Neogloboquadrina pachyderma (dextral-coiling) or Globigerina bulloides dominate during the remainder of the interglacial episodes and during the glacial episodes. Glacial episodes are also marked by particularly high frequencies of Globigerina quinqueloba and Globorotalia scitula. Interglacial episodes are also marked by increases in Globorotalia truncatulinoides, Globigerinoides ruber, and Globigerinella aequilateralis.The planktonic foraminiferal faunal oscillations in the cores are complex and cannot be entirely explained by temperature variation. Other parameters such as salinity, nutrients and biological competitin must influence the faunal oscillations.The faunas suggest no major planktonic foraminiferal faunal boundaries migrated across the area between 37°N and 40°N in the central North Atlantic during the last 300,000 years.     

大鼠局灶性脑缺血后扩布性阻抑的发作及电针对其影响

目的：观察Wistar大鼠局灶性脑缺血后扩布性阻抑（SD）的发作情况及缺血后电针的影响。方法：线检法闭塞大鼠大脑中动脉,制备局灶性脑缺血模型。用神经电生理、神经病理等方法检测局灶性脑缺血后3h内SD发作情况及电针“合谷”穴（LI4）对SD的影响。结果：电针可减少局灶性脑缺血时SD的发作。结论：电针减少局灶性脑缺血时SD的发作,可能与电针缩小局灶性脑梗塞体积有关。     

Control of REM sleep: an aspect of the regulation of physiological homeostasis.

Since REM sleep is characterized by a suspension of the hypothalamic integration of homeostatic regulations, it has been assumed that the duration of both REM sleep episodes and of the time interval between the end of one episode and the beginning of the following episode may be regulated according to sleep related processes and the homeostatic needs of the organism. A series of studies performed on the rat has shown that REM sleep episodes occur as two basic types: single REM sleep episodes, that are separated by intervals > 3 min and sequential episodes, that are separated by intervals < or = 3 min and appear in a cluster. Moreover, it has been observed that, in this species, a change in REM sleep occurrence is caused by a modification in the number of episodes and not in their duration. With respect to this, sleep deprivation and recovery are characterized by a decrease and an increase, respectively, in the number of sequential REM sleep episodes, but the number of single episodes tends to be kept constant. The central aspects of this kind of regulation have been examined biochemically in the preoptic-anterior hypothalamus, an area involved in the control of autonomic and sleep related processes. The results show that the accumulation of adenosine 3':5'-cyclic monophosphate (cAMP) is impaired, in this region, during sleep deprivation and appears to return to the control levels, during the recovery, with a rate inversely related to the degree of the previous deprivation. Moreover, it has been observed that the systemic administration of DL-propranolol and LiCl reduces cAMP accumulation mainly in the preoptic-anterior hypothalamus; this condition is concomitant with a reduction in REM sleep occurrence.     

The use of screening episodes linked to CIN3 and invasive cancer registrations to study outcomes from the NHS Cervical Screening Programme

Objective: To examine how NHS cervical screening data can be collected and analysed in order to evaluate women’s screening histories as episodes rather than as individual smears. Design: Analysis of routine cervical screening data grouped into screening episodes for a cohort of women regarding episodes starting in a given year. Setting: NHS Cervical Screening Programme. Population: Data from four Health Authorities (now eight Primary Care Trusts) from the NHS Cervical Screening Programme with primary smears (first in an episode) taken between 1 April 1999 and 31 March 2000. Methods: Cytology information obtained from the call/recall (‘Exeter’) computer system was linked to cervical intraepithelial neoplasia (CIN) 3 and invasive cancer outcome information obtained from cancer registries. Screening histories were divided into episodes, each starting with a primary smear that was followed up to episode closure or, for episodes still open followed for an average 4.25 years, from the primary smear. The episode was divided into two parts (up to referral to colposcopy and following the referral). The outcomes of the episodes are described including referral rate to colposcopy and CIN3 and invasive cancer rates by factors such as age. Main outcome measures: Episode histories and rates of referral to colposcopy, CIN3 and invasive cancer. Results: There were 176 923 episodes from 176 319 women (1.003 episodes per woman) followed up to March 2004, the date at which the first phase of information accrual ceased. Of these episodes, 172 100 (97.3%) were closed either by a negative smear referring the woman back to routine recall or by default (defined as no smear recorded within 21 months following a smear requiring an action of repeat or refer to colposcopy). The remaining 4823 (2.7%) of episodes were still open, of which in 3121 (1.8%) the woman had been referred to colposcopy and in 1702 (1.0%) no referral decision had been made. Referral rates to colposcopy varied by age from 5.7% in women aged 20–24 years down to 0.9% in women aged 60–64 years. The overall efficiency of screening was highest for woman aged about 30 years, with a CIN3 detection rate of eight per 1000 women and a positive predictive value (for CIN3 or worse) of referral to colposcopy of 21%. Conclusion: The study has shown that routinely collected NHS cervical screening data can be combined to give information on complete episodes, allowing important performance measures to be studied. We suggest that in future information in the NHS screening system should be structured to facilitate such analysis and to allow cytology and histology information to be readily linked.     

Impact of a Community-Based Lymphedema Management Program on Episodes of Adenolymphangitis (ADLA) and Lymphedema Progression - Odisha State,India

Background

Lymphedema management programs have been shown to decrease episodes of adenolymphangitis (ADLA), but the impact on lymphedema progression and of program compliance have not been thoroughly explored. Our objectives were to determine the rate of ADLA episodes and lymphedema progression over time for patients enrolled in a community-based lymphedema management program. We explored the association between program compliance and ADLA episodes as well as lymphedema progression.

Methodology/Principal Findings

A lymphedema management program was implemented in Odisha State, India from 2007–2010 by the non-governmental organization, Church''s Auxiliary for Social Action, in consultation with the Centers for Disease Control and Prevention. A cohort of patients was followed over 24 months. The crude 30-day rate of ADLA episodes decreased from 0.35 episodes per person-month at baseline to 0.23 at 24 months. Over the study period, the percentage of patients who progressed to more severe lymphedema decreased (P-value  = 0.0004), while those whose lymphedema regressed increased over time (P-value<0.0001). Overall compliance to lymphedema management, lagged one time point, appeared to have little to no association with the frequency of ADLA episodes among those without entry lesions (RR = 0.87 (0.69, 1.10)) and was associated with an increased rate (RR = 1.44 (1.11, 1.86)) among those with entry lesions. Lagging compliance two time points, it was associated with a decrease in the rate of ADLA episodes among those with entry lesions (RR = 0.77 (95% CI: 0.59, 0.99)) and was somewhat associated among those without entry lesions (RR = 0.83 (95% CI: 0.64, 1.06)). Compliance to soap was associated with a decreased rate of ADLA episodes among those without inter-digital entry lesions.

Conclusions/Significance

These results indicate that a community-based lymphedema management program is beneficial for lymphedema patients for both ADLA episodes and lymphedema. It is one of the first studies to demonstrate an association between program compliance and rate of ADLA episodes.     

Covariance among premating, post-copulatory and viability fitness components in Drosophila melanogaster and their influence on paternity measurement

In polyandrous mating systems, male fitness depends on success in premating, post-copulatory and offspring viability episodes of selection. We tracked male success across all of these episodes simultaneously, using transgenic Drosophila melanogaster with ubiquitously expressed green fluorescent protein (i.e. GFP) in a series of competitive and noncompetitive matings. This approach permitted us to track paternity-specific viability over all life stages and to distinguish true competitive fertilization success from differential early offspring viability. Relationships between episodes of selection were generally not present when paternity was measured in eggs; however, positive correlations between sperm competitive success and offspring viability became significant when paternity was measured in adult offspring. Additionally, we found a significant male × female interaction on hatching success and a lack of repeatability of offspring viability across a focal male's matings, which may underlay the limited number of correlations found between episodes of selection.