Is fecundability associated with month of birth? An analysis of 19th and early 20th century family reconstitution data from The Netherlands

The relationship between fecundability and month of birth was investigated in a cohort of 1526 women who married between 1802 and 1929, using only women whose first marriage occurred before the age of 35 years. On the basis of their time to pregnancy (TTP, calculated as time between wedding and first birth minus gestational length), women were categorized into two groups: fecunds (TTP up to 12 months or prenuptial conceptions, n = 1348) and subfecunds (TTP >18 months, n = 118). By use of logistic regression, cosinor functions with a period of 1 year or 6 months and variable shift and amplitude were fitted through the monthly odds of subfecunds versus fecunds. The best fitting curve was unimodal, with a zenith in September (P = 0.13 for H0: no differences). Exclusion of childless women (n = 36, minimum follow-up 5 years) from the subfecunds led to a similar curve (P < 0.01), while childless women, as compared with fecunds, showed a birth distribution that was best represented with a bimodal curve with zeniths in January and July (P = 0.06). This study provides evidence for the existence of differences in fecundability by month of birth. The cause of this relationship is unclear, but may lie in a melatonin-dependent circannual variability of the quality of the oocyte.     

13C-urea breath test in Helicobacter pylori diagnosis and eradication. Correlation to histology, origin of ''false'' results, and influence of food intake

Obliterative or constrictive bronchiolitis is characterized by narrowing of the small airways, due to submucosal and peribronchiolar fibrosis, with chronic obstruction. The vast majority of cases of bronchiolitis obliterans are associated with other diseases and only few cases are idiopathic. We report on the main computed tomography (CT) methods used study obliterative bronchiolitis, the CT findings and the differential diagnosis with other diseases. The dynamic study of alveolar ventilation with CT uses inspiratory and expiratory CT or high-resolution CT (HRCT), spiral dynamic CT or HRCT with advanced image display, ultrafast CT. In abnormal cases HRCT shows direct and indirect signs of small airways disease. The most common (> 80%) sign of obliterative bronchiolitis is the so-called mosaic oligohemia, with low attenuating lobules, caused by air trapping and best seen on expiratory CT, associated with blood flow redistribution to more normal lobules; this finding simulates the ground-glass pattern from infiltrative lung disease. Differential diagnosis is more difficult in the presence of true ground-glass patterns associated with diffuse bronchiolar obstruction and also with mosaic oligohemia due to pulmonary vascular disease and pulmonary emphysema. HRCT can distinguish these diseases and dynamic CT is more sensitive than functional tests in detecting regional abnormalities and air trapping. The combination of HRCT, rapid volumetric scanning and advanced image display is a powerful tool study the normal and abnormal features of bronchiolar function and alveolar ventilation.     

Early detection of visual field progression in glaucoma: a comparison of PROGRESSOR and STATPAC 2

AIM: To compare the performance of PROGRESSOR (pointwise linear regression) and STATPAC 2 (comparison with baseline values) in detecting early deterioration in the visual fields of glaucoma patients. METHODS: Visual field series from 19 untreated normal tension glaucoma eyes which were deteriorating on clinical grounds were analysed by PROGRESSOR and STATPAC 2. Progression criteria for PROGRESSOR were (1) inner points: slope < -1 dB/year, p < 0.05 and (2) edge points: slope < -2 dB/year, p < 0.05. Criteria for STATPAC 2 were p < 0.05 change probability for any point on three consecutive fields. Detection time was defined as the time interval between the initial field and the first field in which at least one progressing point was identified. Detection times produced by the two techniques were compared. RESULTS: PROGRESSOR and STATPAC 2 agreed on progression in all 19 eyes. Mean detection time for PROGRESSOR was 1.077 (SD 0.985) years and for STATPAC 2 was 2.161 (1.357) years. PROGRESSOR detected progression sooner than STATPAC 2 in 18 eyes (p < 0.01), Wilcoxon matched pairs signed rank test). PROGRESSOR detected progression earlier by a mean of 1.085 (0.936) years. CONCLUSIONS: PROGRESSOR consistently detected progression earlier than STATPAC 2. The PROGRESSOR software is a useful tool for the early detection of visual field deterioration in glaucoma.     

Active transport of nitrofurantoin across the mammary epithelium in vivo

Nitrofurantoin is a commonly used urinary tract antibiotic that has been found at high concentrations in human milk. In vivo studies in rats were carried out to determine the mechanism by which this drug crosses the mammary epithelium. Lactating rats were gavage-fed with nitrofurantoin, and their milk and plasma levels of the antibiotic were measured at intervals up to 8 hr. The average milk-to-plasma (M/P) ratio, calculated from the areas under the milk and plasma curves, respectively, was 23 compared with a ratio predicted to be about 0.3 on the basis of lipid partitioning and protein binding determinations. M/P ratios for two nitrofurantoin congeners were also calculated. The neutral compound furazolidone had a M/P ratio of about 1, as predicted, whereas the basic compound furaltadone had a M/P ratio of 3.49 compared with a predicted ratio of 1.4. These data suggest that nitrofurantoin and, to a lesser extent, furaltadone are actively transported across the mammary epithelium into milk.     

Abrogation of glomerular injury in nephrotoxic nephritis by continuous infusion of interleukin-6

Interleukin-6 (IL-6) has been reported to have pro- and anti-inflammatory effects. It has also been shown to cause mesangial cell proliferation in vitro and has been suggested as a mediator of injury in proliferative nephritis. We have assessed the effects of continuous infusion of human recombinant (hr) IL-6, by osmotic minipump, on the degree of glomerular injury, and on glomerular and interstitial cell proliferation, in the accelerated autologous phase of nephrotoxic nephritis. Two groups of rats were pre-immunized with 1 mg of normal rabbit IgG in Freund's complete adjuvant. One week later, nephritis was induced by an intravenous injection of 1 ml of rabbit nephrotoxic serum. One day before the induction of nephritis, group 1 (N = 9) was subcutaneously implanted with osmotic minipumps filled with 50 micrograms (200 microliters) of IL-6 (equivalent to a dose of 6 micrograms/day), while in group 2 (N = 11) the minipumps were filled with 200 microliters of normal saline. In group 3 (N = 6) normal rats were infused with 50 micrograms of IL-6 alone. The rats were killed seven days after implantation of minipumps. The administered hrIL-6 was detectable in the circulation within the pathophysiological range, and induced a hepatic acute phase response, as assessed by alpha 2-macroglobulin levels. Continuous treatment with IL-6 resulted in a significant reduction in albuminuria (from 195 +/- 37 mg/20 hr to 60 +/- 15 mg/20 hr on day 1, and from 494 +/- 52 mg/20 hr to 238 +/- 30 mg/20 hr on day 7, P < 0.002) and in the prevalence of glomerular capillary thrombosis (from 19 +/- 3% to 5 +/- 1%, P < 0.002). There was also a reduction in macrophage infiltration (ED1 + ve cells from 524 +/- 34 to 466 +/- 14 per 50 glomeruli, P < 0.02) and activation (ED3 + ve cells from 106 +/- 13 to 42 +/- 5 per 50 glomeruli, P < 0.002). Immunohistology showed fewer interstitial Ia + ve cells (OX3 and OX4) in the IL-6 treated group. Similar results were obtained in a second set of experiments in which the IL-6 treatment was extended until day 14. Kidney sections taken from nephritic rats infused with IL-6 showed no increase in glomerular or interstitial cell proliferation when stained with antibodies to proliferating cell nuclear antigen. There was no difference in the deposition of rabbit IgG or rat IgG along the glomerular basement membrane (GBM), and the titer of rat anti-rabbit IgG was similar in the IL-6 and control treated rats. Infusion of IL-6 alone in normal rats had no functional or pathological effects. In conclusion, these results show that IL-6 has powerful anti-inflammatory effects in a rat model of anti-GBM nephritis, and does not induce mesangial cell proliferation in vivo.     

An epidemic of roller-blade injuries in children

Roller blading is a new and increasingly popular leisure activity in many countries. We reviewed 110 consecutive patients with roller-blade injuries between 1 January and 30 June 1996. The patients ranged from 4 to 14 years in age (mean 6.5 years). Eighty-three (75.4%) sustained injuries to the upper limb and 27 (24.5%) injured the lower limb. Fifty-six patients, were girls and 54 were boys. Of the 110 patients, 79 (72.7%) sustained fractures, 28 (25.4%) soft tissue injuries and 3 (2.7%) dislocations. Eighty-three (75.4%) of the patients wore no protective equipment on the limbs. Four months following injury 103 (93.6%) patients were fully recovered. The mean duration of school absence was 3 days. Subsequently 101 children returned to using roller-blades following injury. Seventy-three (66.3%) of these now use protective equipment. We found that injuries were unrelated to age or duration of roller-blading experience or to the brand-name of roller blades used, and that most of our patients wore no protective equipment at the time of injury.     

Low molecular weight Cooperia oncophora antigens. Potential to discriminate between susceptible and resistant calves after infection

The recognition of low molecular weight proteins by sera obtained during a single oral (primary) infection with 100,000 3rd-stage Cooperia oncophora larvae was studied in calves. Three groups of 6 or 7 calves were selected based on different egg excretion patterns. SDS-gel electrophoresis of adult Cooperia antigen under reducing conditions, followed by Western blotting, revealed that resistance of individual calves to C. oncophora might be related with antibody responses (42 days post infection) against at least 2 protein fragments (14-16 kDa and 27 kDa). The 14-16-kDa protein complex was bound, to some extent, by individual sera from all calves. The intensity of staining was negatively correlated with egg excretion on Day 42 p.i. Calves with high egg counts on Day 21 p.i. either did not or only weakly recognized the 27-kDa band. It has to be established whether the 14-16 kDa (or recombinant 14.2 kDa) provides a tool for immunodiagnostics and whether the 27-kDa fragment can help further unravel immune-mediated resistance to Cooperia.     

The relative contribution of selected carpal bones to global wrist motion during simulated planar and out-of-plane wrist motion

The present study assesses the endocrinological, endometrial histology and vaginal ultrasound profiles of nomegestrol acetate subdermal implant users at varying times after insertion. Follicle stimulatory hormone, luteinizing hormone, oestradiol, progesterone, vaginal ultrasound assessment of the ovaries and the histological dating of the endometrium were serially assessed for a period of 50 days immediately after the insertion, and after at 6 months and 12 months of use. The endocrinological results of this prospective observational clinical trial indicated that 75% of the cycles across the study period in Uniplant users were anovulatory, 63% showing development of a persistent non-luteinized follicle. Anovulatory cycles devoid of follicular development were seen primarily in the first months after Uniplant insertion. Ovulatory cycles represented 25% of the Uniplant cycles. Inadequate luteal phase or disregulation of follicular growth was a common feature of ovulatory cycles. In conclusion, these findings suggest that the contraceptive mechanisms of a single nomegestrol acetate subdermal implant involve prevention of follicular growth, development of a persistent non-luteinized follicle, inadequate luteal phase and disruption of the endometrial architecture.     

Resynchronisation of a diurnal rodent circadian clock accelerated by a melatonin agonist

Using 'jet lag' paradigms involving phase shifts in the light-dark (LD) cycle, we studied the effects of S-20098 on the circadian clock of a diurnal rodent. Arvicanthis mordax, entrained to a regular LD cycle, were subjected to advance shifts (i.e. 4, 6 or 8 h) in the LD cycle and injected with vehicle or the melatonin agonist S-20098 (20 mg/kg) the day of the shift (and also on subsequent days in the 6 h or 8 h shift paradigms). In each condition, S-20098 accelerated by about 30% resynchronization to the new LD cycle. These data, which are the first to demonstrate the chronobiotic effects of a melatonin agonist in a diurnal rodent, provide new insights for the design of human chronopharmacological protocols.