Identification of early environmental risk factors for irritable bowel syndrome and dyspepsia.

BACKGROUND: The role of childhood environment including exposure to infection via siblings and pets in irritable bowel syndrome (IBS) and dyspepsia is relatively unknown. We assessed proxy measures of microbial exposure in early childhood to assess if these are associated with IBS and functional dyspepsia in later life. METHODS: Participants (n = 767, response rate = 53%) were a random population sample from Sydney, Australia who previously responded to a validated survey. IBS and functional dyspepsia were defined using Rome III criteria. Early environmental risk factors assessed included type of birth delivery, premature birth, breastfeeding, bedroom sharing, and pet exposure (the latter two then combined as early hygiene factors) up to 5 years of age. Post infectious IBS (PI-IBS) was assessed by development of IBS following gastroenteritis. KEY RESULTS: In this sample, in adult life 17% developed IBS (of which 20% had PI-IBS) and 12% functional dyspepsia. Development of IBS was associated with childhood factors-a shorter duration of breastfeeding (odds ratios [OR] = 0.87, 95% CI: 0.78-0.97, p = 0.01), sharing a bedroom (OR = 1.89, 95% CI: 1.73-3.08, p = 0.01), exposure to a herbivore pet (OR = 1.65 (1.10, 2.48), p = 0.02), and hygiene factors (OR = 4.39; 95% CI: 1.89-10.21, p = 0.001). The sole factor associated with functional dyspepsia was exposure to a herbivore pet (1.79; 95% CI: 1.19-2.87, p = 0.02). CONCLUSIONS & INFERENCES: Childhood environment factors, particularly bedroom sharing and pet exposure, combined with subsequent risk of microbial exposure are a risk factor for IBS in later life. These associations however need confirmation to rule out any risk of a type I error.

Actin depletion initiates events leading to granule secretion at the immunological synapse.

Cytotoxic T lymphocytes (CTLs) use polarized secretion to rapidly destroy virally infected and tumor cells. To understand the temporal relationships between key events leading to secretion, we used high-resolution 4D imaging. CTLs approached targets with actin-rich projections at the leading edge, creating an initially actin-enriched contact with rearward-flowing actin. Within 1 min, cortical actin reduced across the synapse, T cell receptors (TCRs) clustered centrally to form the central supramolecular activation cluster (cSMAC), and centrosome polarization began. Granules clustered around the moving centrosome within 2.5 min and reached the synapse after 6 min. TCR-bearing intracellular vesicles were delivered to the cSMAC as the centrosome docked. We found that the centrosome and granules were delivered to an area of membrane with reduced cortical actin density and phospholipid PIP2. These data resolve the temporal order of events during synapse maturation in 4D and reveal a critical role for actin depletion in regulating secretion.

'They're not witches. ' Young children and their parents' perceptions and experiences of Child and Adolescent Mental Health Services.

BACKGROUND: Recent initiatives have emphasized the ongoing need to include children in healthcare research, which is relevant to the development of both paediatric and mental healthcare services. Our aim was to contribute children and their parents' perceptions and experiences of Child and Adolescent Mental Health Services (CAMHS), with the objective of providing guidance for those wishing to improve inclusivity and empowerment. METHOD: We performed a thematic analysis of interview data taken from 11 children (9 boys, 2 girls, aged 8-12) and their parents (12 mothers, 2 fathers), who had recently been referred to CAMHS for mental health and educational problems. RESULTS: Three core themes emerged from the data. Fear of the unknown refers to emotional apprehension due to uncertainty of what happens in CAMHS. However children also provided useful reassurances for future service users. Therapeutic engagement refers to the importance of being listened to and building up good relationships with professionals. Finally making services acceptable was discussed in terms of issues of accessibility, session tolerances and suggestions for the development of child-centred services. CONCLUSIONS: Children were able to provide potentially useful opinions of CAMHS. In a time of limited resources it is imperative that the voices of children and their parents are acknowledged in order to improve accessibility and experiences within CAMHS.

The effect of aerobic exercise in the maintenance treatment of depression.

We investigated the efficacy of aerobic exercise alongside antidepressant medication as an adjuvant maintenance treatment for depression. Fifty patients in remission were randomly assigned to either medication only or medication plus exercise. Assessment of psychopathology was made at 6-weekly intervals (for 24 weeks) using the Hamilton Rating Scale for Depression. The medication-plus-exercise group showed significantly more improvement at 12 and 24 weeks than the medication-only group. This study adds to a growing evidence base that suggests aerobic exercise is worthy of further development in the treatment of depressive disorders.

The effects of adenocaine (adenosine and lidocaine) on early post-resuscitation cardiac and neurological dysfunction in a porcine model of cardiac arrest.

AIM: Return of spontaneous circulation (ROSC) elicits ischaemia/reperfusion injury and myocardial dysfunction. The combination of adenosine and lidocaine (AL, adenocaine) has been shown to (1) inhibit neutrophil inflammatory activation and (2) improve left ventricular function after ischaemia. We hypothesized that resuscitation with adenocaine during early moments of cardiopulmonary resuscitation (CPR) attenuates leucocyte oxidant generation and myocardial dysfunction. METHODS: Pigs were randomized to: (1) sham (n=7), (2) cardiac arrest (CA; n=16), or 3) cardiac arrest+adenocaine (CA+AL; n=12). After 7 min of electrically induced ventricular fibrillation, start of CPR was followed by infusion of saline (CA) or adenocaine (CA+AL) for 6 min. Haemodynamics, cardiodynamics (pressure-volume loops) and leucocyte superoxide anion generation were assessed. Neurological function was evaluated after 24h by histology and neurological deficit score (0=normal; 500=brain dead). RESULTS: Rate of ROSC was comparable between groups: CA group 11/16 and CA+AL group 7/12 p=0.57). Cardiac index transiently increased after ROSC in both groups. Left ventricular dysfunction demonstrated by a rightward shift of the intercept of end-systolic pressure-volume relations in CA was avoided in the CA+AL group. Leucocyte superoxide anion generation 2h after ROSC was significantly attenuated in the CA+AL group compared to the CA group. Neurological deficit scores [CA: median: 17.5(IQR:0-75) and CA+AL: 35(IQR:15-150)] and histopathological damage were comparable in both groups (p=0.37). CONCLUSION: Infusion of adenocaine during early resuscitation from CA significantly improved early post-resuscitation cardiac function and attenuated leucocyte superoxide anion generation, without a change in post-ROSC neurological function. (IACUC protocol number 023-2009).

Ischemia-reperfusion increases transfection efficiency of intracoronary adenovirus type 5 in pig heart in situ.

Efficiency of intracoronary (IC) adenoviral vector transfection is impaired by the vascular endothelium. Ischemia and substances that increase vascular permeability (sodium nitroprusside, nitroglycerin) may augment adenoviral vector transfection efficiency (TE). We tested whether TE of adenoviral vector following IC infusion is improved by nitrates or by ischemia. Fluoroscopically guided angioplasty balloon catheters occluded the coronary artery in Yorkshire pigs and delivered adenoviral type 5 vector encoding the luciferase gene (Ad5Luc, 10(11) viral particles). TE (luciferase activity) was minimal and was not augmented by IC co-administration of 50 µg/min sodium nitroprusside to nonischemic myocardium. Two (but not one) 3-min episodes of occlusion tended to increase luciferase activity (p=0.06), and luciferase activity was further increased by IC co-administration of nitroglycerin (p<0.001). After 75 min of coronary artery occlusion, luciferase activity was greater than with shorter periods of ischemia, and was significantly greater in the ischemia-reperfused zone compared to the border zone 3 and 14 days after infusion; there was no transfection in nonischemic myocardium. IC delivery of Ad5Luc into post-ischemic myocardium caused no local inflammation or hemodynamic instability. We conclude that the uptake of IC Ad5 to ischemic reperfused myocardium validates use of IC Ad5 delivery protocols in future human gene therapy trials in patients following myocardial ischemia.

Adhesive epicardial corticosteroids prevent postoperative atrial fibrillation.

BACKGROUND: Postoperative atrial fibrillation remains a common cause of morbidity. Although epicardial drug delivery can increase efficacy and reduce side effects, it is impractical for postoperative atrial fibrillation because pericardial bleeding/effusion and drainage cause rapid drug elimination. Fibrin glue sprayed on the epicardium is vigorously adherent, allowing an admixed drug to remain in contact with the heart. The purpose of the present study was to evaluate a novel corticosteroid-fibrin glue mixture applied to the atrial epicardium at the time of surgery for prevention of postoperative atrial tachyarrhythmias. METHODS AND RESULTS: Talc was instilled into the pericardium in 15 dogs to simulate postoperative inflammation. Pacemakers were implanted to monitor arrhythmias. A mixture of triamcinolone and fibrin glue (Tisseel) was sprayed onto the atria of the treatment animals (n=9), whereas control animals (n=6) received Tisseel or nothing. After 1 week, pacemaker interrogation quantified postoperative atrial tachyarrhythmias (atrial rate >200 bpm) burden. Excised hearts underwent histological examination and tensile strength testing. postoperative atrial tachyarrhythmias occurred in 100% of control animals but only 33% of treatment animals (P=0.027). The median time (25th percentile, 75th percentile) in tachycardia was 5.5 hours (2.7, 12.6) per day in the control group, compared with 0 hours (0, 0.2) in the treatment group (P=0.001). Severe inflammation was present in 6 of 6 control animals and 1 of 9 treatment animals (P=0.001). The tensile strength of a healing left atriotomy was not significantly different between groups. Steroid levels at the time the animals were killed were very low (median of 0.22 µg/dL [0.18, 0.23]). CONCLUSIONS: A mixture of triamcinolone and fibrin glue sprayed onto the atria reduced postoperative atrial tachyarrhythmias and reduced inflammatory cell infiltration. There was no change in the tensile strength of a healing atriotomy and plasma steroid levels were low. Clinical trials of this approach are warranted.

Minilaparotomy-assisted vaginal hysterectomy.

OBJECTIVES: To determine the feasibility and acceptability of minilaparotomy-assisted vaginal hysterectomy. METHODS: A prospective pilot study in a general hospital was conducted. Twenty patients who were on the waiting list for abdominal hysterectomy were included in the study. All these patients had one or more relative contraindications to vaginal hysterectomy. The hysterectomy procedure was started vaginally in all cases. A minilaparotomy incision was performed to complete the procedure if vaginal hysterectomy was not feasible. Results were analyzed on the intention to treat basis. RESULTS: The procedure was successfully completed as intended in 19/20 patients (95%). Six patients had the procedure completed vaginally (30%). Thirteen patients had the procedure completed with minilaparotomy assistance (65%). The mean operative time was 63+/-24.8 min (+/-S.D.). The median estimated blood loss was 155 ml (range: 20-800). One bladder injury occurred. The overall post-operative complication rate was 35% (7/20). This included urinary retention necessitating catheterization for 24 h (n=3), urinary infection (n=2), vaginal infection (n=1) and wound hematoma (n=1). The mean post-operative pain score on a scale from 1 to 10 was 3.1. The overall patient satisfaction based on a scale from 1 to 10 was 9.23 (range: 8-10). CONCLUSIONS: Minilaparotomy-assisted vaginal hysterectomy is a feasible and safe procedure. Our results suggest that this approach is potentially useful in increasing the proportion of hysterectomies performed vaginally.

Endovenous laser: a new minimally invasive method of treatment for varicose veins--preliminary observations using an 810 nm diode laser.

BACKGROUND: Long-term success in the treatment of truncal and significant branch leg varicosities, when the saphenofemoral junction (SFJ) and the greater saphenous vein (GSV) are involved, depends on the elimination of the highest point of reflux and the incompetent venous segment, and is best achieved by surgical ligation and stripping. Minimally invasive alternatives in the treatment of varicose veins with SFJ and GSV incompetence have been tried over the years to increase patient comfort, reduce cost and risk, and allow implementation by a wide variety of practitioners resulting in varying degrees of success depending on the fulfillment of the above two premises and the effectiveness of the method used. OBJECTIVE: To demonstrate a novel way to use laser energy through an endoluminal laser fiber for the minimally invasive treatment of truncal varicosities that eliminates the highest point of reflux and the incompetent segment. METHODS: Patients were treated with 810 nm diode laser energy administered endovenously through a bare-tipped laser fiber (400-750 microm). Vein access for endoluminal placement of the fiber through a catheter was achieved by means of percutaneous or stab wound incision under ultrasound guidance and local anesthesia. Exact placement of the fiber was determined by direct observation of the aiming beam through the skin and by ultrasound confirmation. RESULTS: Preliminary short-term postprocedure results (up to 1 year, 2 months after treatment) in the endovenous laser treatment of 40 greater saphenous veins in 33 patients indicate a 100% rate of closure with no significant complications. In addition, a 2-year experience of 80 cases of isolated branch varicosities (Giacomini, anterolateral branch, etc.) also shows a 100% rate of closure. CONCLUSION: Early results of our endoluminal laser methodology indicate a very effective and safe way to eliminate SFJ incompetence and close the GSV. With proper patient selection, the ease of methodology and the reduced risk and cost associated with endovenous laser treatment may make it a successful minimally invasive alternative for a wide group of patients that previously would have required ligation and stripping.

The risk of carcinogenesis from radiographs to pediatric orthopaedic patients.

This study set out to determine whether cumulative radiograph exposure of children significantly increases their risk of radiation-induced carcinogenesis or hereditary defects. Records of children treated for idiopathic scoliosis, hip dysplasia, or leg-length discrepancy between 1980 and 1993 at the Shriners Hospital in Spokane, WA, were retrospectively reviewed. Total radiation and organ dose exposures were calculated using information from individual radiology reports. Surgically treated idiopathic scoliosis patients had the largest total radiation skin entrance and organ dose exposures. This group's risks for developing leukemia, breast cancer, or a heritable defect, respectively, were 0.8%, 2.1%, and 3.0% higher than baseline risks. The other treatment groups had increased carcinogenic risks of <1%. The use of serial radiographs during the treatment of idiopathic scoliosis, hip dysplasia, and leg-length discrepancy appears relatively safe. The increased risk of carcinogenesis or hereditary defects in these patients is minimal.

Magnetic resonance imaging diagnosis, sonographically directed percutaneous aspiration, and arthroscopic treatment of a painful shoulder ganglion cyst associated with a SLAP lesion.

A 30-year-old, right-handed man presented with the insidious onset of right shoulder pain associated with overhead activities. Magnetic resonance imaging revealed a perilabral ganglion cyst associated with a SLAP lesion (lesion of the superior labrum, both anterior and posterior). After unsuccessful treatment with sonographically directed percutaneous aspiration of the cyst, arthroscopic techniques were employed to intra-articularly decompress the cyst and stabilize the labral tear.

NHLBI workshop summary. Research needs and opportunities related to respiratory health of women.

To summarize, the overwhelming conclusion of the participants was that relatively little is known about respiratory health and disease in women. Much work will be required to obtain even the most basic information upon which hypotheses for future research can be developed and to determine whether pulmonary biology differs between men and women and between women of various ages. The many recommendations and suggestions generated at the workshop should serve to underscore the unique opportunities for research in the field of respiratory health of women.

The effect of time in a new job on hospitalization rates for accidents and injuries in the U.S. Navy, 1977 through 1983.

The incidence of accidental injury hospitalizations among Navy enlisted men during the period 1977 through 1983 was analyzed by paygrade, type of duty station, and external cause of accident to determine whether time in a new job affected an individual's risk of injury and subsequent hospitalization. For personnel assigned to shore duty, the highest incidence of injury occurred during the first few weeks at a new job, then decreased sharply, eventually leveling off after several months. This trend was not present for sea-based personnel. Shore-based personnel had significantly elevated risks of hospitalization from athletic-, fall-, automobile-, motorcycle-, and machinery-related accidents during the first few weeks in a new job compared with sea-based personnel. The leading external causes of injury (motorcycles, automobiles, and athletics) did not change appreciably over time among E2 through E9 personnel.

Cardiac morbidity and mortality associated with occupational exposure to 1,2 propylene glycol dinitrate.

Myocardial infarction and angina pectoris are conditions long associated with occupational exposure to nitroglycerin and related explosives. Cardiac sentinel events in selected munitions workers exposed to the related nitrated ester 1,2 propylene glycol dinitrate were identified and studied. Potentially exposed workers experienced significantly increased relative morbidity compared with control groups. There was no difference in hospitalizations for cardiac arrhythmias. The only cardiovascular mortality occurred in the control groups. The total number of cases was small. Possible sources of bias and causal speculations are discussed.

Hospitalizations for accidents and injuries in the US Navy: environmental and occupational factors.

An epidemiologic analysis of accidental injury hospitalizations was conducted to determine if risk varied by seniority, cause, or duty status for major operational and support activities in the US Navy. Computerized archival medical data were used to select all male enlisted personnel who were hospitalized due to an accidental injury during the period 1977 to 1979 (N = 21,295). Comparison of hospitalization rates between shore-based and sea-based personnel revealed that duty aboard destroyers, replenishment ships, and conventional carriers significantly increased an individual's risk of injury. An inverse relationship was observed between injury risk and seniority. Athletic, automobile, and motorcycle accidents accounted for 63% of all off-duty hospitalizations; machinery, falls, and miscellaneous accidents were the most frequent (56%) causes of on-duty hospitalizations. A positive and significant correlation observed between on-duty and off-duty hospitalizations suggests that common personal attributes may operate in both settings to exacerbate injury risk. Identification of high-risk groups will help focus preventive and corrective efforts.