The detection of adducts in human cervix tissue DNA using 32 P-postlabelling: a study of the relationship with smoking history and oral contraceptive use

³² was used to measure DNA adducts in the human cervix. Adductlevels were compared with patient smoking histories and contraceptiveuse. DNA adducts were found in 43 out of 58 samples. The numberof adducts ranged from 0.2 to 59.5 adducts/10⁸ nucleotides,though no significant difference was found to exist betweenthe number of DNA adducts detected and the smoking history ofeach patient. In contrast, a significant difference at the 1%probability level was found between the adduct levels obtainedfrom the cervical DNA of smokers who had used oral contraceptivesand smokers who did not. Autoradiograms revealed a variety ofadduct patterns. Some were found to have a diagonal zone ofradioactivity which migrated from the origin of the TLC plate.Other autoradiograms revealed the presence of additional adductspots located in the upper regions of the TLC plate, whereasothers revealed the presence of these adduct spots alone. Theorigin of the adduct spots located in the upper regions of theTLC plate is unknown.     

Qualitative and quantitative assessment of the circadian rhythm of cortisol in pregnancy

The effect of pregnancy on the circadian rhythm and diurnal excursion of plasma cortisol and urinary free corticoids was examined in a sequential study during the second and third trimester and 6 to 12 weeks post partum. Hourly blood samples from six subjects and 8-hour urine collections from eight subjects were obtained around the clock. While the circadian rhythm was maintained during gestation, plasma cortisol levels (24-hour mean, nadir, peak, and nadir-peak excursion) increased. The relative excursion of plasma cortisol (expressed as the percentage of deviation from the 24-hour mean) exhibited remarkable blunting compared with postpartum values. This pregnancy-associated blunting of plasma cortisol excursion was indicated by a significant reduction in the: (1) mean peak and nadir excursion, (2) integrated area between the percent deviation curve and the 24-hour mean, and (3) mean slope of the major incremental and decremental segments of the percent deviation curve. The circadian rhythm and diurnal excursion of plasma cortisol were reflected in urinary free corticoid values. Mean 24-hour urinary free corticoid concentrations increased 180% during gestation over nonpregnant levels. Nadir concentrations of urinary free corticoids in pregnancy exceeded peak nonpregnant levels. The gestational rise of metabolically active free cortisol and adrenocorticotropin (ACTH), and the pregnancy-associated blunting of the excursion of plasma cortisol may be explained by an autonomous source of ACTH during gestation.     

The evolution of breast cancer risk assessment

Breast cancer risk assessment is in the process of refinement, largely due to the potential for pharmacologic risk reduction. In the 1970s, benign tissue changes were assigned relative risk (RR) values. The 1980s witnessed the introduction of mathematical models for calculating risk. Genetic counseling and testing appeared in the 1990s. Now in 2002, we are witnessing efforts to improve risk assessment by actively searching for cellular 'atypia' through nipple aspirate fluid (NAF), ductal lavage, and random fine needle aspiration (FNA). One deficiency plagues any approach to predicting breast cancer based on historical risk factors--exclusion of the 70% majority of women who develop breast cancer without any identifiable risk factors. Realizing that the long-term goal of breast cancer risk assessment should be tissue and/or serum-based strategies, the authors introduce the Oklahoma Breast Cancer Project, a tissue bank designed to augment research devoted to molecular biologic markers of risk.     

Progesterone receptors A and B differentially modulate corticotropin-releasing hormone gene expression through a cAMP regulatory element

Corticotrophin-releasing hormone (CRH) plays a major role in mechanisms controlling human pregnancy and parturition. Gene regulation by progesterone may be a key point in the control of placental CRH production. Studies in primary placental ceils show that antagonism of progesterone activity or production by RU486 or trilostane leads to an increase in CRH promoter activity. This effect can be reversed by the addition of progesterone. Overexpression of progesterone receptor A (PRA) or glucocorticoid receptor resulted in a decrease in CRH promoter activity following progesterone treatment, whereas an increase in promoter activity was observed with overexpressed PR-B.     

Estrogen receptor-mediated down-regulation of corticotropin-releasing hormone gene expression is dependent on a cyclic adenosine 3＇ ,5＇-monophosphate regulatory element in human placental syncytiotrophoblast cells

Placental CRH plays a major role in the mechanisms controlling human pregnancy and parturition. Understanding how placental CRH production is regulated is therefore of importance. Previously we have shown that placental expression of CRH peptide and mRNA are inhibited by estrogens, in contrast to the stimulatory effects of estrogen on hypothalamic CRH production. Our current study found that in placental cells cotransfected with a CRH promoter construct and an estrogen receptor-alpha expression vector results in a differential regulation whereby 17beta estradiol (E2) decreased and the putative pure estrogen antagonist, ICI 182780,     

In vivo corneal confocal microscopy in keratoconus

PURPOSE: To evaluate the corneas of keratoconic subjects using in vivo confocal microscopy. METHODS: Slit scanning confocal microscopy was used to evaluate the central cornea of one eye of each of 29 keratoconic subjects (mean age 31 +/- 10 years; range 16-49 years). Quantitative aspects of corneal morphology were compared against data from control subjects. RESULTS: Compared with normal control corneas, epithelial wing cell nuclei were larger (p < 0.0001) and epithelial basal cell diameter was larger (p < 0.05) in the keratoconic cornea. Many of the keratoconic corneas investigated showed increased levels of stromal haze and reflectivity, which appeared to be related to the presence of apical scarring on slit lamp examination. A grading scale was devised to quantify the levels of haze. This scale was shown to provide a measure of the level of scarring present. The anterior keratocyte density (AKD) and posterior keratocyte density were 19% lower (p < 0.0001) and 10% lower (p = 0.004) than in controls, respectively. The reduction in AKD was significantly associated with three factors: a history of atopy, eye rubbing and the presence of corneal staining. The mean endothelial cell density in keratoconus was 6% greater than that of normal controls (p = 0.05). The level of endothelial polymegethism was shown not to be different between keratoconic subjects and matched controls (paired t-test: t = 1.82, p = 0.08). CONCLUSIONS: Confocal microscopy demonstrates significant quantitative alterations of corneal morphology in keratoconus.     

Evidence,Theory and Context: Using intervention mapping to develop a worksite physical activity intervention

Background  

The workplace is an ideal setting for health promotion. Helping employees to be more physically active can not only improve their physical and mental health, but can also have economic benefits such as reduced sickness absence. The current paper describes the development of a three month theory-based intervention that aims to increase levels of moderate intensity physical activity amongst employees in sedentary occupations.     

Steroids for intubated croup masking airway haemangioma

Recently, the beneficial role of steroids for acute laryngotracheobronchitis has been more clearly defined for both intubated and unintubated patients. However, corticosteroids also improve the clinical signs of airway haemangiomata. Two patients are described who illustrate how this can be a source of diagnostic confusion.     

Immunological factors in milk from Brazilian mothers delivering small-for-date term neonates

Breast milk samples from three groups of Brazilian women were evaluated: G1, mothers delivering term babies of low birth weight (n=16); G2, mothers delivering preterm babies of appropriate birth weight (n = 20); G3, mothers delivering term babies of appropriate birth weight ( n = 30). Milk samples were obtained at 48 h and on the 7th, 15th, 30th and 60th days after delivery and they were analyzed for lysozyme and total IgA levels and for the presence of specific antibodies against Poliovirus types I, II, III, Rotavirus, Herpes simplex virus, Varicella zoster and Cytomegalovirus. The groups were not statistically different in relation to mother's age, parity, type of delivery or socio-economic levels. IgA levels were higher in both low-birth-weight groups (G1 & G2) compared to the control group (G3) throughout the study period. Lysozyme levels decreased up to the 15th day, increasing thereafter up to the 60th day in all groups. Specific antibodies were detected throughout the study period, with no differences among groups. We conclude that breast milk composition of mothers delivering low-birth-weight babies (G1 & G2) was similar despite the different gestational ages.     

High-dose versus low-dose bovine surfactant treatment in very premature infants

The aim of the study was to determine if high-dose bovine surfactant (Alveofact, initially 100 mg/kg birth weight) would improve oxygenation compared with low-dose surfactant (50 mg/kg birth weight) administered intratracheally within 1 h after birth. Inclusion criteria included gestational age 24–29 weeks and birth weight 500–1500 g, intubation and mechanical ventilation, absence of congenital malformations and bacterial infections. Retreatment was considered if the fraction of inspired oxygen (FiO₂) was > 0.4 (dose 50 mg/kg birth weight). The primary endpoint was level of oxygenation (PaO₂/ FiO₂) 2 h after treatment. The study design was a sequential analysis using a triangular test with alpha = 0.05 and 95% power to detect a 25 % improvement in the endpoint. Oxygenation was improved significantly with high-dose ( n = 42) compared to low-dose treatment ( n =48): 30.9±15.0 kPa (231.5±112.7 mmHg) versus 24.1±15.7 kPa (180.6±118.0 mmHg) (mean ± SD). The survival rate was 83% in both groups and the incidence of pulmonary interstitial emphysema was 33% versus 14% with the high-dose treatment. We conclude that high-dose surfactant significantly improved oxygenation and reduced lung barotrauma. An initial dose greater than 50 mg/kg birth weight of surfactant is required for optimal acute response.