Elevated Exhaled Nitric Oxide in Adolescents Is Associated With Incident Allergic Symptoms: A Prospective Cohort Study.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is a marker of type-2 inflammation in the airways. Elevated FeNO may precede the development of allergic disease. The aim of the present study was to investigate the association between elevated FeNO and the development of allergic symptoms. METHODS: A total of 959 adolescents from the general population and their parents completed a standardized questionnaire. Lung function and FeNO were assessed at baseline. Four years later, 921 of these individuals (96%) completed the same version of the baseline questionnaire. RESULTS: Adolescents with self-reported incident allergic symptoms to cat (n=50) or dog (n=33) had higher baseline FeNO (P<.001) than those without allergic symptoms to cat and dog at both time points (n=776 and n=838, respectively). Adolescents with incident allergic symptoms to pollen did not have elevated baseline FeNO. The adjusted odds ratio (aOR [95%CI]) for incident allergic symptoms to cat was 4.2 (2.2-8.0) times higher if FeNO was >75th percentile (vs <75th percentile) at baseline. This was consistent after exclusion of individuals with reported asthma, wheeze, or rhinitis at baseline (8.6 [3.0-24.1]). CONCLUSION: Elevated FeNO in adolescents was associated with an increased risk of developing allergic symptoms to cat and dog allergens, but not to pollen allergens, after 4 years.

Parental smoking and development of allergic sensitization from birth to adolescence.

BACKGROUND: The relation between secondhand tobacco smoke (SHS) exposure and the development of allergic sensitization in children is unclear. The aim of this study was to determine whether maternal smoking during pregnancy and postnatal SHS exposure contributes to the development of allergic sensitization in children and adolescents up to 16 years of age. METHODS: We included 3316 children from a birth cohort followed up for 16 years. SHS exposure and symptoms of allergic disease were assessed using repeated parental questionnaires. Serum immunoglobulin E against eight common inhalant and six food allergens was assessed at ages 4, 8, and 16 years with ImmunoCAP. The association between SHS exposure and sensitization was explored using logistic regression and generalized estimating equations. RESULTS: Exposure to SHS in infancy without prior exposure in utero was associated with an excess risk of food sensitization at age 4 years (OR 1.47, 95% CI 1.08-2.00), with comparable ORs at ages 8 and 16 years. In longitudinal analyses, an overall association was indicated between SHS in infancy and food sensitization up to age 16 years (OR 1.24, 95% CI 0.98-1.56). Maternal smoking during pregnancy was unrelated to sensitization up to 16 years of age. When sensitization was combined with concurrent symptoms of allergic disease, SHS in infancy was associated with an overall elevated risk of eczema with sensitization (OR 1.62, 95% CI 1.20-2.18). CONCLUSIONS: SHS exposure in infancy appears to increase the risk of sensitization to food allergens up to age 16 years, as well as eczema in combination with sensitization.

Seventy-five-million-year-old tropical tetra-like fish from Canada tracks Cretaceous global warming.

Newly discovered fossil fish material from the Cretaceous Dinosaur Park Formation of Alberta, Canada, documents the presence of a tropical fish in this northern area about 75 million years ago (Ma). The living relatives of this fossil fish, members of the Characiformes including the piranha and neon tetras, are restricted to tropical and subtropical regions, being limited in their distribution by colder temperatures. Although characiform fossils are known from Cretaceous through to Cenozoic deposits, none has been reported previously from North America. The modern distribution of characiforms in Mexico and southern Texas in the southernmost United States is believed to have been the result of a relatively recent colonization less than 12 Ma. The new Canadian fossils document the presence of these fish in North America in the Late Cretaceous, a time of significantly warmer global temperatures than now. Global cooling after this time apparently extirpated them from the northern areas and these fishes only survived in more southern climes. The lack of early Cenozoic characiform fossils in North America suggests that marine barriers prevented recolonization during warmer times, unlike in Europe where Eocene characiform fossils occur during times of global warmth.

Maternal haemorrhage.

Maternal haemorrhage is the leading cause of preventable maternal death worldwide and encompasses antepartum, intrapartum, and postpartum bleeding. This review highlights factors that predispose to severe bleeding, its management, and the most recent treatment and guidelines. Advances in obstetric care have provided physicians with the diagnostic tools to detect, anticipate, and prevent severe life-threatening maternal haemorrhage in most patients who have had prenatal care. In an optimal setting, patients at high risk for haemorrhage are referred to tertiary care centres where multidisciplinary teams are prepared to care for and deal with known potential complications. However, even with the best prenatal care, unexpected haemorrhage occurs. The first step in management is stabilization of haemodynamic status, which involves securing large bore i.v. access, invasive monitoring, and aggressive fluid management and transfusion therapy. Care for the patient with maternal bleeding should follow an algorithm that goes through a rapid and successive sequence of medical and surgical approaches to stem bleeding and decrease morbidity and mortality. With the addition of potent uterotonic agents and the advent of minimally invasive interventional radiological techniques such as angiographic embolization and arterial ligation, definitive yet conservative management is now possible in an attempt to avoid hysterectomy in patients with severe peripartum bleeding. If these interventions are inadequate to control the bleeding, the decision to proceed to hysterectomy must be made expeditiously. Recombinant factor VIIa is a relatively new treatment that could prove useful for severe coagulopathy and intractable bleeding.

Symptoms to pollen and fruits early in life and allergic disease at 4 years of age.

BACKGROUND: The predictive value of reported early symptoms to pollen or fruits on later allergic disease is unclear. Our aim is to evaluate if symptoms to pollen and/or to fruits early in life are associated with allergic disease and sensitization to pollen at 4 years. METHODS: The study included 3619 children from the Barn (Children), Allergy, Milieu, Stockholm, Epidemiology project (BAMSE) birth cohort. Reported symptoms of wheeze, sneeze or rash to birch, grass or weed, symptoms (vomiting, diarrhea, rash, facial edema, sneeze, or wheeze) to fruits including tree-nuts at 1 or 2 years of age, and definitions of asthma, rhinitis and eczema at 4 years were derived from questionnaire data. Sensitization to pollen allergens was defined as allergen-specific IgE-antibodies to any pollen (birch/timothy/mugwort) > or =0.35 kU(A)/l. RESULTS: At 1 or 2 years of age, 6% of the children were reported to have pollen-related symptoms, 6% had symptoms to fruits, and 1.4% to both pollen and fruits. Children with symptoms to both pollen and fruits at 1 or 2 years of age had an increased risk for sensitization to any pollen allergen at age 4 (OR(adj) = 4.4, 95% CI = 2.1-9.2). This group of children also had a substantially elevated risk for developing any allergic disease (asthma, rhinitis, or eczema) at 4 years irrespective of sensitization to pollen (OR(adj) = 8.6, 95% CI = 4.5-16.4). CONCLUSIONS: The prevalence of reported symptoms to pollen and fruits is very low in early childhood. However, children with early symptoms to both pollen and fruits appear to have a markedly elevated risk for allergic disease.

Dopamine-induced stress signaling in COS-7 cells transfected with selectively vulnerable muscarinic receptor subtypes is partially mediated via the i3 loop and antagonized by blueberry extract.

Muscarinic receptors (MAChRs) are intimately involved in various aspects of both neuronal and vascular functioning, and there is selective oxidative stress sensitivity (OSS) among MAChR subtypes, with M1, M2, and M4 showing>OSS. OSS was assessed by determining the loss of ability of the cell to extrude or sequester Ca2+ following oxotremorine-induced depolarization following exposure to dopamine (DA) subtypes in transfected COS-7 cells. This OSS can be prevented by pretreatment with blueberry (BB) extract. Present studies were carried out to determine BB treatment of the cells transfected with wild type, truncated or chimeric [where the i3 loop of one receptor was switched with the i3 loop of the other; i.e., M1(M3i3) and M3(M1i3)] receptors would alter DA-induced changes in calcium buffering and would confer protection through alterations in pMAPK, pCREB or PKC signaling. These findings also suggest that BB may antagonize OS effects by lowering activation of pCREB and possibly PKCgamma induced by DA. In the truncated and chimeric receptors, results indicated that BB reduced OSS in response to DA in M1-transfected cells. However, BBs were also effective in preventing these Ca2+ buffering deficits in cells transfected with M1 receptors in which the i3 loop had been removed, but only partially enhanced the protective effects of the M3 i3 loop in the M1(M3i3) chimerics. A similar partial effect of BBs was seen in the M3(M1i3) chimerics which showed increased OSS in response to DA. It appears that antioxidants found in BBs might be targeting additional sites on these chimerics to decrease OSS.

First trimester screening for congenital heart disease.

Most obstetrical practices in the United States offer pregnant women at least one ultrasound during pregnancy. This prenatal ultrasound is usually scheduled at around 18 to 20 weeks gestation. Both the American Institute of Ultrasound in Medicine and the American College of Obstetricians and Gynecologists recommend that the four-chamber view be included to screen for congenital heart disease. Recently, many investigators have attempted to screen for congenital heart disease earlier in pregnancy. Fetal nuchal translucency thickness traditionally used to screen for fetal aneuploidy by transvaginal and abdominal ultrasound has also been shown to identify a large proportion of fetuses with congenital heart disease. Recent studies have also reported congenital heart disease in chromosomally normal fetuses with increased nuchal translucency thickness in the first trimester. Advances in ultrasound technology and training over the last 10 years allow greater visualization rates of the four-chamber view and outflow tracks in the late first trimester (up to 90% visualization at 13 weeks). Fetal echocardiography in the first trimester may be indicated for fetuses at risk for congenital heart disease. In this article we present a review of the most recent and ongoing clinical and basic research to support an earlier first trimester approach to diagnosing congenital heart defects.

Angiography contrast agents interact with serine proteinases. The molecular structure of the model system elastase/iohexol.

Pancreatic elastase was co-crystallised with iohexol, a tri-iodo benzenic contrast agent used in angiography analyses. The X-ray analysis of the complex reveals the presence of three molecules of iohexol associated with the proteinase with low occupancy factors. Two iohexol molecules are located in and near the active site of the enzyme and provide a model for explaining the inhibition of the hemostatic system, one of the major and inconvenient side effect associated with these chemicals.

A pilot study of whole body hyperthermia and carboplatin in platinum-resistant ovarian cancer.

The aim of this study was to determine whether the addition of whole body hyperthermia (WBH) to carboplatin (CBDCA) can induce responses in patients with platinum-resistant ovarian cancer. 16 pretreated patients with platinum-resistant ovarian cancer were entered on a Systemic Hyperthermia Oncological Working Group (SHOWG) study; (14 patients were eligible with 14 evaluable for toxicity and 12 for response). The patients were treated with WBH (Aquatherm) 41.8 degrees C x 60 min in combination with carboplatin (CBDCA) (area under the curve (AUC) of 8) every 4 weeks. Disease status was evaluated every two cycles. Patients were treated for a maximum of six cycles. One patient had a complete response (CR) and 4 had a partial response (PR). 4 patients had stable disease (SD). 3 patients had progressive disease (PD). 2 patients were unevaluable: 1 had a bowel obstruction shortly after her first treatment; the second patient achieved a CR, but only had one treatment secondary to an idiosyncratic reaction to sedative drugs. 2 patients entered on study were ineligible, as they did not meet criteria for platinum resistance; 1 entered a CR and 1 had SD. Dose-limiting toxicity, which required CBDCA dose reductions, was grade 4 thrombocytopenia. Other toxicities included neutropenia (grade 3/4), and nausea and/or vomiting. Consistent with preclinical modelling, these results suggests that 41.8 degrees C WBH can overcome platinum resistance in ovarian cancer. These observations suggest further investigation of the therapeutic potential of WBH in a group of patients who historically fail to respond to salvage therapies is warranted.

Salivary gland transplantation: a canine model.

Impaired salivary function with resultant severe dryness of the mouth, or xerostomia, may occur in association with a variety of systemic disorders or therapies. No adequate treatment exists for this debilitating condition, which impedes normal oral function, in particular alimentation and phonation. This study explores the feasibility of salivary gland autotransplantation, using a canine model. A salivary gland with its duct and surrounding blood vessels still attached was excised and reimplanted in the dog's thigh by anastomosing the graft's blood vessels to the femoral artery and vein. The duct was sutured to an artificial orifice cut in the thigh's skin, from which the saliva was collected. Salivary secretion was induced by a single intravenous bolus of pilocarpine (5 mg). Preoperative (normal) salivation was measured by collecting saliva from the gland in situ. Periodic functional studies showed normal saliva production during the first month after grafting, after which the salivary flow was reduced by 35% over the next 2 months. This reduction was interpreted as a sign of disuse atrophy resulting from the lack of autonomic innervation. To overcome this impediment, oral pilocarpine (5 mg/day) was administered to the recipient dog, after which normal levels of saliva were excreted through the graft during the 3-month follow-up period. The quality of the graft saliva was assessed by its protein and electrolyte levels, which showed close to normal values.

Two active junctional pacemakers manifested by atrioventricular dissociation and junctional captures.

A case of atrioventricular dissociation with RP-dependent abrupt prolongation of ventricular cycles is presented. The prolongation was less than expected with concealed junctional captures. It is assumed that resetting of an upper junctional pacemaker allowed impulses from a lower one to escape.

Conformational features of C-glycosyl compounds: crystal structure and molecular modelling of "methyl C-gentiobioside".

The crystal of "methyl C-gentiobioside" (methyl 8,12-anhydro-6,7-dideoxy-D-glycero-D-gulo-alpha-D-gluco-trideca pyranoside) (C14H26O10) is triclinic, space group P1, with a = 1.0181 (6) nm, b = 0.8093 (5) nm, c = 0.5066 (4) nm, alpha = 96.03 (5) degrees, beta = 99.94 (5) degrees, gamma = 90.85 (5) degrees. The two D-glucose residues have the 4C1 conformation. The orientation of the beta-(1----6) linkage is characterized by torsion angles phi = 55.9 degrees, psi = 175.1 degrees, and omega = -63.9 degrees. The orientation of the primary hydroxyl group at the non-reducing residue is gauche-trans (omega' = -53.6 degrees). There is no intramolecular hydrogen bond. Molecules are held together by a network of hydrogen bonds involving all of the hydroxyl groups. This crystal structure is the first experimental characterization of a "C-disaccharide". Unlike methyl gentiobioside, which has a high level of conformational flexibility, the "C-disaccharide" has a restricted flexibility. Each of the low-energy conformers in vacuo has a value of phi centered about 60 degrees, in agreement with the solid state conformation, and the exo-anomeric effect is no longer predominant.

Phosphorous pentachloride chemical burn--a slowly healing injury.

A 51-year-old chemical engineer sustained phosphorous pentachloride partial skin thickness burns over 20 per cent of his body surface area. Although macroscopically and microscopically the wound seemed to be superficial, the course of clinical healing of this injury was very slow and painful. Retrospectively this burn should have been treated by early excision and grafting.

Silver sulphadiazine-induced haemolytic anaemia in a glucose-6-phosphate dehydrogenase-deficient burn patient.

A 20-year-old soldier sustained 35 per cent body surface area burns by open flames. He was treated with topical application of 1 per cent silver sulphadiazine (SSD) twice daily. Four days postburn he developed acute haemolytic anaemia. Withdrawal of SSD was followed by complete recovery. A glucose-6-phosphate dehydrogenase (G6PD) deficiency was proven by pathological Motulski tests. Although the hazards of SSD are well indicated by the manufacturers, there appear to be no written reports of haemolysis induced by this drug in G6PD-deficient patients.

Use of buried skin implants after recurrent failure of conventional skin grafting in a massive burn: the renewal of an old technique.

The technique of burying small pieces of skin under old granulation tissue after recurrent failure of conventional skin grafting is described in a patient with 95 per cent full skin thickness burns. This method of treatment, which was described in the past and neglected, is of value for massive burns or grafting in difficult areas. The technique is described again and the relevant literature reviewed.

Cyclosporin A treatment failed to extend skin allograft survival in two burn patients.

Prolongation of skin allograft survival by immunosuppression of burn casualties has been reported sporadically during the past two decades. Recently cyclosporin A (CycA) has been used effectively for such an indication. We report here two paediatric patients with extensive burns (85-95 per cent BSA) treated with fresh, family-related skin allografts that were rejected during CycA treatment after 14-18 days. One of these children survived while the other died with candida sepsis.

Chemical burn due to contact with soda lime on the playground: a potential hazard for football players.

Two football players were treated for chemical burns of their genitalia and medial thighs caused by contact with soda lime used to line a playground. The cases are reported and the unusual mechanism causing the injury is described.

Cryopreserved cadaveric allografts for treatment of unexcised partial thickness flame burns: clinical experience with 12 patients.

Partial thickness burns (PTB) usually heal within 3 weeks. Prevention of infection and desiccation of the wounds are crucial for optimal healing. Early tangential excision of the burn eschar and allografting prevent deepening of the burns, and are therefore advocated for treatment with the best functional and aesthetic results. For superficial partial thickness burns (SPTB) conservative use of topical antimicrobial agents with frequent dressing changes are implemented. We compared the conservative treatment for PTBs and SPTBs to grafting cryopreserved cadaveric allografts with no prior excision. Twelve patients with flame PTB areas were allografted after mechanical debridement without excision of the burn wounds. The allografts were cadaveric skin cryopreserved by programmed freezing and stored at -180 degrees C for 30-48 months. Matching burns for depth and area were treated with silver sulfadiazine (SSD) one to two times daily until healing or debridement and grafting were required. It was found that 80 per cent of the cryopreserved allografts adhered well and 76 per cent of the treated areas healed within 21 days, whereas only 40 per cent of the SSD-treated burns healed within 21 days. Partial thickness burns can be treated successfully with viable human allografts (cryopreserved cadaveric skin) with no prior surgical excision. The burn wounds heal well within 3 weeks. For deep partial thickness burns (DPTB) treatment with allografts has no advantage if they have not been previously excised.

Terrorist bombing with a 'Molotov cocktail' inside travelling cars: an old weapon for a new burn syndrome?

The 'Molotov cocktail' terrorist weapon which is thrown into a travelling car has given a new type of injury to people who sustain massive smoke inhalation together with disfiguring burns of face, thighs, hands and chest, and post-traumatic psychological disorder. The combination of petrol ignition with the synthetic fumes inside the care is a unique occurrence with a high morbidity and mortality which is difficult to treat and to manage. We propose to show that the combination of all the above components can be defined as the 'Molotov cocktail' burn syndrome.

Very deep burns of the hand due to low voltage electrical laboratory equipment: a potential hazard for scientists.

A low voltage (24 V) electrical deep burn of the hand injured a professor of applied physics when performing an experiment in his laboratory. The potential hazard of the equipment is described, the injuries are reported and the literature is reviewed.