B cells have been reported to promote graft rejection through alloantibody production. However, there is growing evidence that B cells can contribute to the maintenance of tolerance. Here, we used a mouse model of MHC-class I mismatched skin transplantation to investigate the contribution of B cells to graft survival. We demonstrate that adoptive transfer of B cells prolongs skin graft survival but only when the B cells were isolated from mice housed in low sterility “conventional” (CV) facilities and not from mice housed in pathogen free facilities (SPF). However, prolongation of skin graft survival was lost when B cells were isolated from IL-10 deficient mice housed in CV facilities. The suppressive function of B cells isolated from mice housed in CV facilities correlated with an anti-inflammatory environment and with the presence of a different gut microflora compared to mice maintained in SPF facilities. Treatment of mice in the CV facility with antibiotics abrogated the regulatory capacity of B cells. Finally, we identified transitional B cells isolated from CV facilities as possessing the regulatory function. These findings demonstrate that B cells, and in particular transitional B cells, can promote prolongation of graft survival, a function dependent on licensing by gut microflora.
Rituximab (a monoclonal antibody directed against CD 20) therapy can be acutely complicated by infusion reactions and cardiac arrhythmia on rare occasions. We report the first case of a new onset left bundle branch block (LBBB) after rituximab therapy for Wegener's vasculitis.
Arrhythmia; bundle branch block; rituximab
Myocardial infarction (MI) due to coronary atherosclerosis in young adults is uncommon; rare causes such as cocaine abuse, arterial dissection, and thromboembolism should be considered. A 21-year-old football player, and otherwise healthy African American man, developed chest pain during exercise while bench-pressing 400 lbs. Acute MI was diagnosed based on physical examination, electrocardiography findings, and elevated cardiac enzymes. Coronary arteriography showed a thrombus occluding the proximal left anterior descending artery (LAD). Aggressive antiplatelet therapy with aspirin, clopidogrel, and eptifibatide was pursued, in addition to standard post-MI care. This led to the successful resolution of symptoms and dissolution of the thrombus, demonstrated by repeat coronary arteriography. Five months later, he presented with similar symptoms during exercise after lifting heavy weights, and was found to have another acute MI. Coronary arteriography again showed a thrombus occluding the LAD. No evidence of coronary artery dissection or vasospasm was found. Only mild atherosclerotic plaque burden was observed on both occasions by intravascular ultrasound. A bare metal stent was placed at the site as it was thought this site had acted as a nidus for small plaque rupture and thrombus formation. Elevated serum factor VIII activity at 205% (reference range 60%–140%) was found, a rare cause of hypercoagulability. Further workup revealed a patent foramen ovale during a Valsalva maneuver by transesophageal echocardiography. Both events occurred during weight lifting, which can transiently increase right heart pressure in a similar way to the Valsalva maneuver. In light of all the findings, we concluded that an exercise-related increase in factor VIII activity led to coronary arterial thrombosis in the presence of a small ruptured plaque. Alternatively, venous clots may have traversed the patent foramen ovale and occluded the LAD. In addition to continuing aggressive risk factor modification, anticoagulation therapy with warfarin was initiated with close follow-up.
MI; factor VIII; exercise; myocardial infarction; young; football player
Post-reperfusion syndrome (PRS) is a serious, widely reported complication following the reperfusion of an ischemic tissue or organ. We sought to determine the prevalence, risk factors and short-term outcomes of PRS related renal transplantation. We conducted a retrospective, case-control study of patients undergoing renal transplantation between July 2006 and March 2008. Identification of PRS was based on a drop in mean arterial pressure by at least 15% within 5 minutes of donor kidney reperfusion. Of the 150 consecutive renal transplantations reviewed, 6 patients (4%) met criteria for post-reperfusion syndrome. Univariate analysis showed that an age over 60, diabetes mellitus, Asian race, and extended criteria donors increased the odds of developing PRS by 4.8 times (95% CI [1.2, 20]; P=.0338), 4.5 times (95% CI [1.11, 18.8]; P=.0378), 35.5 times (95% CI [3.94, 319.8]; P=0.0078) and 9.6 times (95% CI [1.19, 76.28] P=0.0115) respectively. Short term follow-up revealed increased graft failure rate within 6 months (6% vs. 16% P=0.0125) and almost twice the number of hospital days post-transplant in PRS cohorts (5.43 ± 2.29 vs. 10.8 ± 7.29 P=<0.0001). Despite limited reporting, PRS appears to be a relatively common complication of renal transplantation and is associated with increase morbidity.
Post reperfusion syndrome; PRS; renal transplant; transplant complications; hypotension.
Autonomic dysfunction is common in patients with the joint hypermobility syndrome (JHS). However, there is a paucity of reported data on clinical features of Postural orthostatic tachycardia syndrome (POTS) in patients suffering from JHS.
This retrospective study was approved by our local Institutional Review Board (IRB). Over a period of 10 years, 26 patients of POTS were identified for inclusion in this study. All these patients had features of Joint Hypermobility Syndrome (by Brighton criterion). A comparison group of 39 patients with other forms of POTS were also followed in the autonomic clinic during the same time. We present a descriptive report on the comparative clinical profile of the clinical features of Postural Orthostatic Tachycardia patients with and without Joint Hypermobility syndrome. The data is presented as a mean±SD and percentages wherever applicable.
Out of 65 patients, 26 patients (all females, 20 Caucasians) had POTS and JHS. The mean age at presentation of POTS was 24±13 (range 10-53 years) vs 41±12 (range 19-65 years), P=0.0001, Migraine was a common co morbidity 73 vs 29% p=0,001. In two patients POTS was precipitated by pregnancy, and in three by surgery, urinary tract infection and a viral syndrome respectively. The common clinical features were fatigue (58%), orthostatic palpitations (54%), presyncope (58%), and syncope (62%).
Patients with POTS and JHS appear to become symptomatic at an earlier age compared to POTS patients without JHS. In addition patients with JHS had a greater incidence of migraine and syncope than their non JHS counterparts.
autonomic dysfunction; joint hypermobility syndrome; postural orthostatic tachycardia
We present an interesting intracardiac electrogram of a dissimilar atrial rhythm in a patient of bi-atrial orthotopic cardiac transplant.
bi-atrial orthotopic cardiac transplant; intracardiac electrogram
To assess the contribution of postnatal factors to failure to thrive in infancy.
11 900 infants from the Avon Longitudinal Study of Parents and Children (ALSPAC), born at 37–41 weeks' gestation, without major malformations and with a complete set of weight measurements in infancy (83% of the original ALSPAC birth cohort) were studied. Conditional weight gain was calculated for the periods from birth to 8 weeks and 8 weeks to 9 months. Cases of growth faltering were defined as those infants with a conditional weight gain below the 5th centile.
Analysis yielded 528 cases of growth faltering from birth to 8 weeks and 495 cases from 8 weeks to 9 months. In multivariable analysis, maternal factors predicting poor infant growth were height <160 cm and age >32 years. Growth faltering between birth and 8 weeks was associated with infant sucking problems regardless of the type of milk, and with infant illness. After 8 weeks of age, the most important postnatal influences on growth were the efficiency of feeding, the ability to successfully take solids and the duration of breast feeding.
The most important postnatal factors associated with growth faltering are the type and efficiency of feeding: no associations were found with social class or parental education. In the first 8 weeks of life, weak sucking is the most important symptom for both breastfed and bottle‐fed babies. After 8 weeks, the duration of breast feeding, the quantity of milk taken and difficulties in weaning are the most important influences.
Background: Autonomic dysfunction is common in patients suffering from multiple sclerosis (MS) and orthostatic dizziness occurs in almost 50% of these patients. However, there have been no reports on postural orthostatic tachycardia syndrome (POTS) in patients suffering from MS.
Methods: The patients were included for analysis in this study if they had POTS with either a prior history of MS or having developed MS while being followed for POTS. Postural orthostatic tachycardia (POTS) is defined as symptoms of orthostatic intolerance(>6months) accompanied by a heart rate increase of at least 30 beats/min (or a rate that exceeds 120 beats/min) that occurs in the first 10 minutes of upright posture or head up tilt test (HUTT) occurring in the absence of other chronic debilitating disorders. We identified nine patients with POTS who were suffering from MS as well. Each of these patients had been referred from various other centers for second opinions.
Results: The mean age at the time of diagnosis of POTS was 49±9 years and eight of the 9 patients were women. Five patients (55%) had hyperlipidemia, 3 (33%) migraine and 2 (22%) patients had coronary artery disease and diabetes each. Fatigue and palpitations (on assuming upright posture) were the most common finding in our patients (9/9). All patients also had orthostatic dizziness. Syncope was seen in 5/9(55%) of patients. Four patients (44%), who did not have clear syncope, were having episodes of near syncope. The presence of POTS in our study population resulted in substantial limitation of daily activities. Following recognition and treatment of POTS, 6/9(66%), patients were able to resume daily activities of living. Their symptoms (especially fatigue and orthostatic intolerance) improved. The frequency and severity of syncope also improved. Three (33%) patients failed to show a good response to treatment.
Conclusion: Patients suffering from MS may manifest autonomic dysfunction by developing POTS. Early recognition and proper management may help improve the symptoms of POTS.
Multiple sclerosis; Postural tachycardia syndrome; syncope; dizziness; fatigue.
We present herein an interesting tracing of a patient who suffered from recurrent episodes of transient loss of consciousness (TLOC) associated with convulsive activity thought to be due to epilepsy or conversion disorder.
Asystole; implantable loop recorder; transient loss of consciousness
Postural orthostatic tachycardia syndrome (POTS) commonly affects women of childbearing age. We report on a 37-year-old woman who developed symptoms of recurrent syncope in the postpartum period. Her head up tilt test and clinical presentation was consistent with POTS.
Scientific controversy and media hype in unexpected infant deaths
infant deaths; SIDS; bedsharing; pacifiers; risk reduction
To determine the combined effects of sudden infant death syndrome (SIDS) risk factors in the sleeping environment for infants who were “small at birth” (pre‐term (<37 weeks), low birth weight (<2500 g), or both).
A three year population based, case‐control study in five former health regions in England (population 17.7 million) with 325 cases and 1300 controls. Parental interviews were carried out after each death and reference sleep of age matched controls.
Of the SIDS infants, 26% were “small at birth” compared to 8% of the controls. The most common sleeping position was supine, for both controls (69%) and those SIDS infants (48%) born at term or ⩾2500 g, but for “small at birth” SIDS infants the commonest sleeping position was side (48%). The combined effect of the risk associated with being “small at birth” and factors in the infant sleeping environment remained multiplicative despite controlling for possible confounding in the multivariate model. This effect was more than multiplicative for those infants placed to sleep on their side or who shared the bed with parents who habitually smoked, while for those “small at birth” SIDS who slept in a room separate from the parents, the large combined effect showed evidence of a significant interaction. No excess risk was identified from bed sharing with non‐smoking parents for infants born at term or birth weight ⩾2500 g.
The combined effects of SIDS risk factors in the sleeping environment and being pre‐term or low birth weight generate high risks for these infants. Their longer postnatal stay allows an opportunity to target parents and staff with risk reduction messages.
SIDS; pre‐term; low birth weight; infant sleeping position; co‐sleeping
Background: Implantable loop recorders (ILR) have been found to be useful in the diagnosis and management of syncope of unclear etiology. The clinical symptoms of abnormalities seen during ILR monitoring have not been adequately studied.
Aim: The aim of this retrospective study was to determine the clinical symptoms which were the best predictors of asystolic or bradycardic responses during ILR monitoring.
Methods: Patients with either asystole or bradycardia recorded during ILR monitoring were analyzed from our database. The clinical characteristics of these patients were compared to the patients with ILR's who did not have recorded bradycardic episodes. The episodes were characterized as being convulsive or nonconvulsive, brief (<5 minutes) or prolonged (> 5 minutes), and having had a prodrome or no prodrome.
Results: Eleven patients (4 males and 7 females; age 39 ±11years) had asystole or bradycardia on ILR monitoring. Eleven patients (2 males and 9 females; age 46±23) had no bradycardiac events. Palpitations, convulsive syncope, prolonged episode, and prodrome were present in 37% vs. 74% (P = 0.125), 62% vs. 0% (P = 0.002), 87% vs. 0% (P=0), and 73% vs. 13% (P=0.009) patients, respectively, in the asystole/bradycardia and non-bradycardia groups. In the asystole/bradycardia group eight patients had bradycardia (HR < 20) for > 10 seconds and three patients had asystole >10 seconds.
Conclusion: Convulsive syncope, prolonged loss of consciousness during syncopal episode, and absence of prodrome or aura are clinical predictors of asystole or bradycardia on ILR monitoring.
Implantable loop recorders; bradycardia; asystole; convulsions.
Introduction: Not all convulsive episodes are due to epilepsy and a number of these have a cardiovascular cause. Failure to identify these patients delays the provision of adequate therapy while at the same time exposes the individual to the risk of injury or death.
Methods: We report on three patients who suffered from recurrent convulsive episodes, thought to be epileptic in origin, who were refractory to antiseizure therapy. Although each patient had undergone extensive evaluation, no other potential cause of his or her seizure like episodes had been uncovered. In each patient placement of an implantable loop recorder (ILR) demonstrated that their convulsive episodes were due to prolonged periods of cardiac asystole and/or complete heart block. In all patients their convulsive episodes were eliminated by permanent pacemaker implantation.
Conclusion: In patients with refractory “seizure' like episodes of convulsive activity of unknown etiology a potential cardiac rhythm disturbance should be considered and can be easily evaluated by ILR placement.
Implantable loop recorders; Convulsions; Syncope.
Aims: To investigate the characteristics of parent–infant bed-sharing prevalence in England.
Methods: Data on night-time sleeping practices from a two year, local, longitudinal study and a three-year, national, cross-sectional study were obtained. A total of 261 infants in North Tees were followed up at 1 and 3 months of age, as were 1095 infants aged 1 week to 1 year from five English health regions.
Results: Data from both studies found that almost half of all neonates bed-shared at some time with their parents (local = 47%, 95% CI 41 to 54; national = 46%, 95% CI 34 to 58), and on any one night in the first month over a quarter of parents slept with their baby (local = 27%, 95% CI 22 to 33; national = 30%, 95% CI 20 to 42). Bed-sharing was not related to younger mothers, single mothers, or larger families, and was not more common in the colder months, at weekends, or among the more socially deprived families; in fact bed-sharing was more common among the least deprived in the first months of life. Breast feeding was strongly associated with bed-sharing, both at birth and at 3 months. Bed-sharing prevalence was uniform with infant age from 3 to 12 months; on any one night over a fifth of parents (national = 21%, 95% CI 18 to 24) slept with their infants.
Conclusion: Bed-sharing is a relatively common practice in England, not specific to class, but strongly related to breast feeding.
Seasonal and circadian variation in the incidence of ruptured abdominal aortic aneurysm (RAAA) has been reported. We explored the role of atmospheric pressure changes on rupture incidence and its relationship to cardiovascular risk factors. During a three year-period, 1st April 1998 and 31st March 2001, data was prospectively acquired on 144 Ruptured Abdominal Aortic Aneurysm (RAAA) presenting to the Regional Vascular Surgery Unit at the Royal Victoria Hospital, Belfast, Northern Ireland. For each patient the chronology of acute onset of symptoms and presentation to the regional vascular unit was recorded, along with details of standard cardiovascular risk factors. During the same period meteorological data including atmospheric pressure and air temperature were recorded daily at the regional meteorological research unit, Armagh. We then analyzed the monthly mean values for daily rupture incidence in relation to the monthly values for atmospheric pressure, pressure change and temperature. Furthermore atmospheric pressure on the day of rupture, and day preceding rupture, were also analyzed in relation to days without rupture presentation and between individual ruptures for various cardiovascular risk factors. Data demonstrated a significant monthly variation in aneurysm rupture frequency, (p<0.03, ANOVA). There was also a significant monthly variation in mean barometric atmospheric pressure, (p<0.0001, ANOVA), months with high rupture frequency also exhibiting low average pressures in the months of April (0.24 +/- 0.04 ruptures per day and 1007.78 +/- 1.23 mB) and September (0.16 +/- 0.04 ruptures per day and 1007.12 +/- 1.14 mB), respectively. The average barometric pressures were found to be significantly lower on those days when ruptures occurred (n=1127) compared to days when ruptures did not occur (n=969 days), (1009.98 +/- 1.11 versus 1012.09 +/- 0.41, p<0.05). Full data on risk factors was available on 103 of the 144 rupture patients and was further analyzed. Interestingly, RAAA with a known history of hypertension, (n=43), presented on days with significantly lower atmospheric pressure than those without, (n=60), (1008.61 +/- 2.16 versus 1012.14 +/- 1.70, p<0.05). Further analysis of ruptures grouped into those occurring on days above or below mean annual atmospheric pressure 1013.25 (approximately 1 atmosphere), by Chi-square test, revealed three cardiovascular risk factors significantly associated with low-pressure rupture, (p<0.05). Data represents mean +/- SEM, statistical comparisons with Student t-test and ANOVA. These data demonstrate a significant association between periods of low barometric pressure and high incidence of ruptured aneurysm, especially in those patients with known hypertension. The association between rupture incidence and barometric pressure warrants further study as it may influence the timing of elective AAA repair.
AIMS—To investigate patterns of infant growth that may
influence the risk of sudden infant death syndrome (SIDS).
DESIGN—Three year population based
case control study with parental interviews for each death and four age
matched controls. Growth was measured from prospective weight
observations using the British 1990 Growth Reference.
SETTING—Five regions in England
(population greater than 17 million, more than 470 000 live births
over three years).
SUBJECTS—247 SIDS cases and 1110controls.
RESULTS—The growth rate from birth
to the final weight observation was significantly poorer among the SIDS
infants despite controlling for potential confounders (SIDS mean change
in weight z score (δzw) = −0.38 (SD 1.40)
v controls = +0.22 (SD 1.10),
multivariate: p < 0.0001). Weight gain was poorer among SIDS infants
with a normal birth weight (above the 16th centile: odds ratio
(OR) = 1.75, 95% confidence interval (CI) 1.48-2.07, p < 0.0001)
than for those with lower birth weight (OR = 1.09, 95% CI
0.61-1.95, p = 0.76). There was no evidence of increased growth
retardation before death.
CONCLUSIONS—Poor postnatal weight
gain was independently associated with an increased risk of SIDS and
could be identified at the routine six week assessment.
the clinical characteristics associated with sudden infant death
syndrome (SIDS) and explained sudden unexpected deaths in infancy (SUDI).
population based, case control study with parental interviews for each
death and four age matched controls.
in England (population, > 17 million; live births, > 470 000).
SUBJECTS—SIDS: 325 infants; explained SUDI: 72 infants; controls: 1588infants.
univariate analysis, all the clinical features and health markers at
birth, after discharge from hospital, during life, and shortly before
death, significant among the infants with SIDS were in the same
direction among the infants who died of explained SUDI. In the
multivariate analysis, at least one apparent life threatening event had
been experienced by more of the infants who died than in controls
(SIDS: 12% v 3% controls; odds ratio (OR) = 2.55; 95% confidence interval (CI), 1.02 to 6.41; explained SUDI: 15% v 4% controls; OR = 16.81;
95% CI, 2.52 to 112.30). Using a retrospective illness scoring system
based on "Baby Check", both index groups showed significant markers
of illness in the last 24 hours (SIDS: 22%
v 8% controls; OR = 4.17; 95% CI, 1.88to 9.24; explained SUDI: 49% v 8%
controls; OR = 31.20; 95% CI, 6.93 to 140.5).
clinical characteristics of SIDS and explained SUDI are similar. Baby
Check might help identify seriously ill babies at risk of sudden death,
particularly in high risk infants.
investigate the relation between pacifier use and sudden infant death
population based, case control study with parental interviews for each
death and four age matched controls.
in England (population > 17 million).
who had died from SIDS and 1300 control infants.
fewer SIDS infants (40%) than controls (51%) used a pacifier for the
last/reference sleep (univariate odds ratio (OR), 0.62; 95% confidence
interval (CI), 0.46 to 0.83) and the difference increased when
controlled for other factors (multivariate OR, 0.41; 95% CI, 0.22 to
0.77). However, the proportion of infants who had ever used a pacifier
for day (66% SIDS v 66% controls) or night
sleeps (61% SIDS v 61% controls) was
identical. The association of a risk for SIDS infants who routinely
used a pacifier but did not do so for the last sleep became
non-significant when controlled for socioeconomic status (bivariate OR,
1.39 (0.93 to 2.07)).
epidemiological evidence and physiological studies are needed before
pacifier use can be recommended as a measure to reduce the risk of SIDS.