Aromatase mRNA expression in individual follicles from polycystic ovaries

Polycystic ovary syndrome (PCOS) is a common reproductive disorder characterized by arrested follicular development prior to selection of a dominant follicle. Dominant follicles produce large amounts of oestradiol but PCOS follicles do not. With several potential aromatase (P450AROM) inhibitors in follicular fluid, the question arises whether P450AROM is expressed in PCOS granulosa cells, but the activity is inhibited, or whether P450AROM is not expressed in PCOS. The purpose of the present study was to determine whether P450AROM mRNA expression is altered in PCOS and to correlate P450AROM mRNA expression in individual follicles with aromatase stimulatory bioactivity and oestradiol in the follicular microenvironments. P450AROM mRNA was measured in individual follicles from 16 PCOS and 48 regularly cycling control women by quantitative polymerase chain reaction (PCR) and correlated with follicular fluid oestradiol concentrations and aromatase stimulating bioactivity measured by the rat granulosa cells aromatase bioassay. Follicular fluid oestradiol was low in all control follicles <7 mm in diameter. Some follicles > or = 7 mm contained elevated oestradiol values (P < 0.01) and all had an androstenedione:oestradiol ratio of <4. Only in granulosa cells from follicles > or = 7 mm with an androstenedione:oestradiol ratio of <4 were P450AROM mRNA levels increased (P < 0.05). These same follicles also contained increased levels of aromatase stimulating bioactivity whereas follicles <7 mm or with androstenedione:oestradiol ratio of >4 contained little or no bioactivity. All PCOS follicles contained low levels of oestradiol, P450AROM mRNA and aromatase stimulating bioactivity similar to size- matched control follicles. These data indicate that P450AROM mRNA expression and oestradiol production begin in developing follicles when they reach approximately 7 mm in diameter. Oestradiol production is low in PCOS follicles because there is insufficient aromatase stimulating bioactivity to increase P450AROM mRNA expression.      

Hysterosalpingo contrast sonography (HyCoSy) with SH U 454 (Echovist) for the assessment of tubal patency

A total of 88 Fallopian tubes from 44 patients was examined with hysterosalpingo contrast sonography (HyCoSy), hysterosalpingogram (HSG), and laparoscopic chromopertubation (LC) in order to assess their relative accuracy for measuring tubal patency. HyCoSy was done by transvaginal ultrasound and the contrast was SH U 454 (Echovist). The flow of multiple fractions of the contrast medium through each Fallopian tube was observed in real time in appropriate imaging planes by means of a transvaginal probe. Compared with laparoscopic results, we found a sensitivity of 85.2%, a specificity of 85.2%, a positive predictive value (PPV) of 71.9%, a negative predictive value (NPV) of 92.9% and concordance (HyCoSy/LC) of 85.2%, while the corresponding values for HSG were sensitivity = 85.2%, specificity = 83.6%, PPV = 69.7%, NPV = 92.7% and concordance (HSG/LC) of 84.1%. Compared with HSG results, HyCoSy obtained a co-positivity of 66.7%, a co-negativity of 81.8% and a concordance of 76.1%. In conclusion, HyCoSy with SH U 454 proved to be a reliable and safe modality for evaluating tubal patency; it is suitable as an outpatient diagnostic procedure to be used before more invasive procedures.      

Combined treatment with enuresis alarm and desmopressin for nocturnal enuresis

Seventy-one children with nocturnal enuresis were enrolled in a controlled trial. The children were allocated to two matched groups. Children in both groups used an enuresis alarm until the end of treatment. Children in the first group were treated with 40/^g of intranasal desmopressin (Desmospray) for up to 6 weeks at the start of treatment with the alarm. During the observation period before treatment there were 2.3 dry nights per week in both groups. At the end of treatment there was a significant difference in the mean number of dry nights per week between the two groups (6.3 in the alarm and desmopressin group and 4.8 in the alarm group) and also in the number of children becoming reliably dry. The combination of desmopressin and alarm was particularly helpful for children with severe wetting and those with family and behavioural problems. Desmopressin, enuresis alarm, nocturnal enuresis
MG Bradbury, Department of Paediatrics and Child Health, St James's University Hospital, Leeds LS9 7TF, UK     

Etheno adducts in spleen DNA of SJL mice stimulated to overproduce nitric oxide

In order to investigate specific DNA damage caused by nitric oxide (NO) induced lipid peroxidation, levels of promutagenic etheno adducts 1,N6- ethenodeoxyadenosine (epsilondA) and 3,N4-ethenodeoxycytidine (epsilondC) were measured in spleen DNA of SJL mice induced to produce high levels of NO by injection of RcsX (pre-B-cell lymphoma) cells. epsilondA and epsilondC levels were quantified by an ultrasensitive immunoaffinity-32P-post-labeling method. Spleen DNA of control mice (n = 5) had background levels of 9.2+/-5.4 epsilondA adducts per 10(9) dA and 13.1+/-5.7 epsilondC adducts per 10(9) dC. In RcsX cell-injected mice (n = 7), levels of these adducts were elevated approximately 6- fold, i.e. 53.9+/-39.4 epsilondA per 10(9) dA and 83.5+/-57.8 epsilondC per 10(9) dC (P < 0.05). Mice injected with RcsX cells and also treated with NG-methyl-L-arginine (NMA), an inhibitor of inducible nitric oxide synthase (n = 6), had significantly reduced levels (P < 0.05) of both epsilondA and epsilondC (13.5+/-5.7 epsilondA per 10(9) dA and 28.2+/- 15.7 epsilondC per 10(9) dC). These findings constitute the first available evidence of formation of etheno adducts associated with NO overproduction in vivo. The adducts were presumably formed from lipid peroxidation products such as trans-4-hydroxy-2-nonenal (HNE), generated via oxidation of lipids by peroxynitrite. The results suggest that etheno-DNA adducts, among other types of damage, may contribute to the etiology of cancers associated with chronic infection/inflammation in which NO is overproduced.      

Precipitants and aetiology of cyclic vomiting syndrome

Thirty-two patients aged 2-22 y with cyclic vomiting syndrome (CVS), and 64 age- and gender-matched controls were assessed to determine the nature, severity, precipitants and associated features of attacks and the incidence of potential aetiological factors. The mean age of onset was 3.5 y. Patients experienced a mean of nine attacks per year, of average duration 2.4 d, and two-thirds missed more than 10 d of school per year. Patients were more likely to have migraine and co-ordination difficulties, a past history of forceps delivery and gastroesophageal reflux than controls. Compared with controls, subjects had a higher incidence of psychological symptoms (38% compared with 19%) and migraine (37% compared with 9%). CVS is a chronic, disabling condition and is a migraine variant, with attacks usually precipitated by stress and intercurrent infections.     

Early child health in Lahore, Pakistan: IX. Perinatal events

In Pakistan there are a number of acute problems related to maternal and infant health in the perinatal period. There is also lack of reliable data needed for the formulation of action strategies. To provide a database 1490 women have been followed from the 5th month of pregnancy in four different areas at various levels of urbanization and socio-economic development. After adjusting for gestational age, the proportion of newborns with weight for length < -2SDS in relation to the Swedish National Standard was 12–31% for boys and 12–25% for girls, the figure being highest in the most deprived area. Preterm birth was infrequent compared with IUGR. The overall prevalence rate of birth defects was 21% out of which 8% were severe defects. The overall perinatal mortality rate was 56/1000 births, with rates of 60, 75, 36 and 33/1000 births for the village, periurban slum, urban slum and the upper middle class. Two thirds of the deaths were related to either a continuation of intrauterine disturbances or severe congenital defects incompatible with life. One third of the deaths were due to infection; mostly diarrhoea, clinical sepsis and ARI. Neonatal mortality was significantly related to birth length (<-2SDS, odds ratio 5.5) and length of gestation (<37 weeks, odds ratio 5.6) and was to a lesser extent related to weight (<-2SDS, odds ratio 2.0) and weight for length (<-2SDS, odds ratio 1.3). Forty percent of the mothers had weight for height below -2SDS, 23–35% had height <-2SDS. Forty percent of mothers from a subset within the cohort had a hemoglobin < 10 gm/dl and 20% showed signs of pre-eclampsia. This presentation raises the issue of expanding the current Child Survival Programs into the perinatal period as well.     

Cohort effects in dynamic models and their impact on vaccination programmes: an example from Hepatitis A

Background  

Infection rates for many infectious diseases have declined over the past century. This has created a cohort effect, whereby older individuals experienced a higher infection rate in their past than younger individuals do now. As a result, age-stratified seroprevalence profiles often differ from what would be expected from constant infection rates.