Airway intervention in adult supraglottitis

Background The timing of aggressive airway intervention in adult epiglottitis is controversial. Aims To correlate Friedman’s staging of epiglottitis on admission with the airway interventions undertaken. Methods A retrospective study of 23 adult patients, mean age 51 years (range 29–81 years), who had been admitted with acute supraglottitis between March 1988 and December 2000 was undertaken. Results Three patients (13%) had airway interventions; two with tracheostomy and one with tracheal intubation. All were Friedman stage III and had rapid symptom progression during the 24 hours prior to admission. Three other stage III patients with symptom progression longer than 24 hours and all the remaining patients (stage II or less) were managed with observation and intravenous therapy. Conclusions Friedman originally advocated airway intervention in any patient stage II or worse, but this intubation threshold should probably be lowered to those patients with rapid-onset stage III (moderate respiratory distress, stridor, respiratory rate >30 per minute, pCO₂ >45mmHg) disease.     

Nature and nurture in novelty seeking

A sample of children (n=92), derived from a representative population sample of healthy young Finns (n=2149), was studied from childhood to adulthood over 14 years to determine whether the childhood environment moderated the effect of dopamine receptor gene (DRD4) polymorphism on novelty seeking (NS). A significant interaction between the DRD4 alleles and environmental variables was observed. When the childhood-rearing environment was more hostile (emotionally distant, low tolerance of the child's normal activity, and strict discipline), the participants carrying any two- or five-repeat alleles of the DRD4 gene had a significantly greater risk of exhibiting NS scores that were above the 10th percentile on a population distribution of 2149 adult Finnish women and men. The genotype had no effects on NS when the childhood environment was more favorable. Although the results are preliminary, pending replication, they nevertheless provide important information on the long-term effects of nurture and nature on NS temperament.     

Group IIA phospholipase A2 content of tears in patients with atopic blepharoconjunctivitis

Background To determine the concentration of group IIA phospholipase A₂ (GIIAPLA₂) in tears of patients with atopic blepharoconjunctivitis (ABC), and to compare it with the GIIAPLA₂ concentration of tears in age-matched healthy controls.Methods The diagnosis of ABC was confirmed with a positive skin prick test and the presence of atopic dermatitis in lids. Conjunctival brush cytology was taken, and the cells including eosinophils, neutrophils, lymphocytes, squamous epithelial cells, columnar epithelial cells, metaplastic changes and the goblet cells were calculated separately. The GIIAPLA₂ concentration of tears was measured with a time-resolved fluoroimmunoassay in 29 patients with ABC (mean age 36.3±12.7 years) and 29 normal subjects (mean age 37.0±12.0 years).Results The GIIAPLA₂ concentration of tears in patients with ABC was 43.8±33.0 µg/ml, and in normal subjects it was 67.1±23.3 µg/ml. The difference was statistically significant (p=0.0018). The concentration of GIIAPLA₂ of tears was lowest in the subgroup of patients with ABC and dry eye (25.8 ±23.6 µg/ml), whereas it was only slightly decreased in patients with ABC and normal tear secretion (56.6±33.3 µg/ml). The difference between these two subgroups was statistically significant (p=0.011). There was no statistically significant correlation between the GIIAPLA₂ concentration of tears and the quantity of different conjunctival cells gathered by the brush cytology. However, an almost significant correlation was found between the GIIAPLA₂ concentration in tears and conjunctival eosinophils.Conclusions The results indicate that in patients with ABC the GIIAPLA₂ content of tears was decreased, without any dependence on the quantity of different conjunctival cells.     

Early degeneration of the knee in diastrophic dysplasia: an MRI study

Magnetic resonance imaging (MRI) findings of 23 patients (13 females, 10 males; 45 knees) with diastrophic dysplasia were examined. The age of the patients ranged from 5 to 40 years (mean 20.5 years). T1- and T2-weighted MR images were obtained. MRI revealed degenerative changes in the articular cartilage of the knees from age 6 years. The subchondral bone of the distal femur was often fragmented, and cartilaginous intrusions from the growth plate into the metaphysis were noted. Menisci developed abnormally. In 43 (96%) of the knees studied, the anterior cruciate ligament was either thinned or rudimentary, or could not be detected. The posterior cruciate ligament was affected in 40 (89%) knees but was at least rudimentary in all patients. In contrast, the patellar tendon was thick and short and the patella was in an inferior position The patella showed bony fragmentation in 32 (71%) knees. The pathologic changes in all joint compartments increased with age, reflecting early degeneration of the knee in this disease.     

Scoliosis in patients with diastrophic dysplasia: a new classification

STUDY DESIGN: Scoliosis in patients with diastrophic dysplasia was analyzed. OBJECTIVES: To study the natural history of scoliosis and to classify the patients with different types of scoliosis. SUMMARY OF BACKGROUND DATA: Typical findings in diastrophic dysplasia are short-limbed short stature, multiple joint contractures, early degeneration of joints, and spinal deformities. The largest studies have reported scoliosis in 37% to 88% of the patients with this rare skeletal dysplasia. The natural history of the deformity is unknown. METHODS: Of the 130 unselected patients, 98 (75%) who were older than 16 years and/or had undergone surgery at the time of the last radiograph were included in the final analysis. These 98 patients included 37 males and 61 females. Their ages at the first radiograph ranged from newborn to 78 years (average, 21 years). The mean follow-up period was 20 years (range, 2-41 years) for 80 patients. Standard standing anteroposterior and lateral radiographs were taken. The degrees of scoliosis, kyphosis, and lordosis were measured according to the Cobb method. Classification of the scoliosis was based on the patient's age at onset of scoliosis, the rate of progression, the magnitude of the scoliosis at the end of growth, and the curve pattern. RESULTS: Of the 98 patients in this study, 86 (88%) had scoliosis. This difference was highly significant statistically (P < 0.001), as compared with the normal population. The frequency of scoliosis was 90% among females and 84% among males. Scoliosis can be divided further into three subtypes: early progressive (11 patients), idiopathic-like (41 patients), and mild nonprogressive (33 patients). One patient had a congenital scoliosis. CONCLUSIONS: Scoliosis is very common in patients with diastrophic dysplasia. The natural history of scoliosis varies from severe deformity with rapid progression to mild deformity without any progression. The authors suggest that the classification described in this report offers a tool for the predicting natural history of scoliosis in diastrophic dysplasia, and for adjusting the timing of surgery in individual patients.     

The effect of age and density of the breast on the sensitivity of breast cancer diagnostic by mammography and ultasonography

Purpose. We studied which, age of the patient or density of the breast accounts for the sensitivity of mammography and ultrasonography (US). Furthermore we studied whether the overall impression on the density of the breast or the density in tumour area accounts for the sensitivity of mammography and ultrasonography. Materials and methods. The material consisted of 572 consecutive histologically and 5 cytologically verified breast cancer cases. Mammography and US examinations were performed immediately before breast cancer operations and information on the findings were received from the original patient files and classified as malignant or benign. The density of breast parenchyma to fatty, mixed or dense in total breast and separately in tumour area was defined by a radiologist group from the original mammograms by comparing to model mammograms. The sensitivity (Se) of mammography and US was compared in 3 age groups (26–49, 50–59 and 60–92) and in the different density classes. Results. Sensitivity of mammography increased by age (density-adjusted OR=0.2, 95%, CI 0.1–0.5) in age group 26–49 compared to age group 60–92) and with fattiness of the breast (age-adjusted OR=0.4, 95%, CI 0.1–1.0 for dense breast parenchyma in tumour area compared to fatty breast). Sensitivity of US was inversely related to age (density-adjusted OR=2.3, 95%, CI 1.0–5.2 in age group 26–49 compared to age group 60–92) and directly related with fattiness of breast (age-adjusted OR=0.5, 95%, CI 0.2–0.9 by dense breast parenchyma in tumour area compared to fatty breast). Density in the tumour area compared to total breast density was related only mariginally better sensitivity both of mammography (0.4 vs. 0.6) and of US (0.5 vs. 0.6). itConclusion. Sensitivity of both mammography and sensitivity of US are independently related both to the age of the patient and to the density of the breast. The effect of age is inverse and that of density parallel between mammography and US on sensitivity. The effect of overall breast density was close to the effect of density at the site of the tumour on the sensitivity of both mammography and US.     

Butadiene diolepoxide- and diepoxybutane-derived DNA adducts at N7-guanine: a high occurrence of diolepoxide-derived adducts in mouse lung after 1,3-butadiene exposure.

Butadiene (BD) is a high production volume chemical and is known to be tumorigenic in rodents. BD is metabolized to butadiene monoepoxide (BMO), diepoxybutane (DEB) and butadiene diolepoxide (BDE). These epoxides are genotoxic and alkylate DNA both in vitro and in vivo, mainly at the N7 position of guanine. In this study, a 32P-post-labeling/thin-layer chromatography (TLC)/high-pressure liquid chromatography (HPLC) assay for BDE and DEB adducts at the N7 of guanine was developed and was used in determining the enantiomeric composition of the adducts and the organ dose of BD exposure in lung. Exposure of 2'-deoxyguanosine (dGuo), 2'-deoxyguanosine-5'-phosphate (5'-dGMP) and 2'-deoxyguanosine-3'-phosphate (3'-dGMP) to racemic BDE followed by neutral thermal hydrolysis gave two products (products 1 and 2) that were identified by MS and UV and NMR spectroscopy as a diastereomeric pair of N7-(2,3,4-trihydroxybutan-1-yl)-guanines. Exposure of dGuo nucleotides to RR/SS DEB (also referred to as dl DEB) followed by thermal depurination resulted in a single product coeluting with the BDE product 1. If the reaction mixture of BDE and 5'-dGMP was analyzed by HPLC before hydrolysis of the glycosidic bond, four major nucleotide alkylation products (A, B, C and D) with identical UV sepectra were detected. The products were isolated and hydrolyzed, after which A and C coeluted with product 1 and B and D coeluted with the product 2. The major adduct of DEB-exposed 5'-dGMP was N7-(2-hydroxy-3,4-epoxy-1-yl)-dGMP (product E). A 32P-post-labeling assay was used to detect BDE- and DEB-derived N7-dGMP adducts in DNA. Levels of adducts increased with a dose of BDE and DEB and exhibited a half life of 30 +/- 3 (r = 0.98) and 31 +/- 4 h (r = 0.95), respectively. Incubation of DEB-modified DNA at 37 degrees C at neutral pH for up to 142 h did not lead to an increase of N7-(2,3,4-trihydroxybutan-1-yl)-dGMP in the DNA. These observations led to the conclusion that the N7-(2,3, 4-trihydroxybutan-1-yl)-dGMP adducts in DNA can be used as a marker of BDE exposure and that N7-(2-hydroxy-3,4-epoxy-1-yl)-dGMP adducts are related to DEB exposure. Dose-related levels of BDE- and DEB-derived adducts were detected in lungs of mice inhaling butadiene. Most of the N7-dGMP adducts (73%; product D) were derived from the 2R-diol-3S-epoxide of 1,3-butadiene. The data presented in this paper indicate that in vivo, 98% of N7-dGMP alkylation after BD exposure is derived from BDE, and approximately 2% of the adducts were derived from DEB and BMO.