Associations between androgen and Vitamin D receptor microsatellites and postmenopausal breast cancer.

We investigated the association between polymorphism in the androgen receptor (AR) and vitamin D receptor (VDR) genes and breast cancer risk in a large population-based case-control study of genetically homogenous Swedish women. We successfully determined both AR CAG(n) and VDR A(n) genotype in 1,502 women with invasive breast cancer and in 1,510 control women. We did not find any associations between AR or VDR microsatellite lengths and breast cancer when we used a priori determined cutoffs (/=22 repeats for AR and /=19 for VDR) to define long and short alleles. There was statistically significant interaction between VDR genotype and parity, such that women with two short alleles had a halved risk for breast cancer, irrespective of parity, compared with nulliparous women with two long alleles. Homozygosity for the long VDR allele was associated with a more advanced clinical stage at diagnosis. In exploratory analyses, we determined cutoffs based on visual inspection of distributions of allele lengths among cases and controls and found that women carrying two alleles with <20 AR CAG(n) repeats had an increased risk for breast cancer, odds ratio of 1.67 (95% confidence interval, 1.17-2.38), compared with those with two alleles with >/=20 repeats. Women carrying two VDR alleles with <21 A(n) were also at an increased risk, odds ratio of 1.26 (95% confidence interval, 1.04-1.51). Our data do not support major roles for AR or VDR polymorphism as breast cancer risk factors. However, we did find an interaction between VDR genotype and parity that remains to be corroborated.     

Effects of restrained cervical mobility on voluntary eye movements and postural control

The effects of restrained cervical mobility on pursuit eye movements (PEMS), voluntary saccades and postural control, as measured by posturography, were studied in 11 healthy subjects whose cervical spine movement had been restrained for 5 days by means of a rigid neck-collar. At day 5 mean peak velocity of voluntary saccades at amplitudes of 40 degrees and 60 degrees was significantly reduced, as was mean peak gain of PEMs at a stimulus velocity of 50 degrees/s; the variance of body position in vibration-induced body sway was significantly increased, but there was no difference in variance of galvanically-induced body sway or in velocity of vibration-induced body sway. The results suggest that restriction of cervical movements per se affects voluntary eye movements, a conclusion also consistent with findings in patients with tension headache. Restriction of cervical movement only marginally affects postural control.     

Effect of proprioceptor stimulation on postural stability in patients with peripheral or central vestibular lesion

Body sway in upright stance at rest and after inducing proprioceptor stimulation, elicited by vibration applied to the calf or neck muscles, was studied in 11 patients with peripheral lesion and in 17 patients with central vestibular lesion. The responses were compared with those of 20 normal subjects. Vibratory stimulus was applied at five different frequencies, ranging from 32 to 150 Hz, and at a constant amplitude of 2.1 mm. Postural stability was measured with a force platform in terms of average deviation of body position (ADBP) analyzed in relation to the individual maximum support distance in the anterio-posterior direction. In patients with peripheral vestibular lesion ADBP was moderately increased, compared to normal subjects, when the calf muscles were exposed to vibration under eyes closed conditions (i.e. no visual information available); stimulation of neck muscles both under eyes open and eyes closed conditions and stimulation of calf muscles with open eyes produced an ADBP of the same magnitude as in controls. In patients with central vestibular lesion, proprioceptor stimulation of calf and neck muscles caused increased ADBP whether with eyes open or closed. The ADBP induced by stimulation of neck muscles was significantly greater in patients with a central lesion than in those with a peripheral vestibular lesion. The results indicate that patients with peripheral lesion differ from those with central vestibular lesion in their reaction to proprioceptor stimulus; and that in patients with central vestibular lesion proprioceptor stimulation of the neck muscles produces disproportionately powerful cervico-collic reflexes.     

Postural compensation in children with congenital or early acquired bilateral vestibular loss

The relative roles of different receptor systems in compensating for vestibular loss were studied in 18 children (12 to 16 years of age) with congenital or early acquired bilateral vestibular loss (BVL) and impaired hearing, and compared to that in 33 normal children (9 to 16 years of age). Postural stability was studied with posturography evaluating the velocity of anterior-posterior body sway. With closed eyes the increase of sway velocity did not differ between the groups, either with or without simultaneous proprioceptive disturbances when the subjects were standing on a bare surface. Body sway velocities were found to increase more in subjects with a BVL than in normal children when subjects were standing on foam rubber. When proprioceptive cues were disturbed, body sway velocities increased in both groups, but significantly more in children with BVL when subjects stood on foam rubber. This occurred both with and without open eyes.     

The relationship between caloric response, oculomotor dysfunction and size of cerebello-pontine angle tumours

Seventy-nine consecutive patients, 70 patients with acoustic neurinomas (ACN) and 9 patients with cerebello-pontine angle tumours of other etiology (o-CPA) were analysed with respect to tumour size and the result of the caloric and oculomotor tests. The size of the tumour was judged by the largest diameter calculated from the computerized tomography. A highly significant linear relationship between tumour size and caloric side difference was found for the group of ACN patients who had normal oculomotor function. A unilateral loss of caloric response on the tumour side was found in 75% of the ACN patients with tumours larger than 20 mm, but not in any of the ACN patients with tumours smaller than 10 mm. Oculomotor dysfunction (OMD), defined as disturbed pursuit eye movements and/or gaze nystagmus was frequently found in the patients with ACN larger than 20 mm (77%), and was present in all but one of the o-CPA patients. However, the caloric response on the tumour side was significantly more impaired in the group of ACN patients with OMD than in the o-CPA group. A combined view of the oculomotor and caloric test results offers a possibility to obtain a rough estimate of tumour size as well as to distinguish ACNs from other types of tumours in the cerebello-pontine angle.     

Changes in visual acuity from 4 to 12 years of age in children operated for bilateral congenital cataracts

AIMS: To investigate the long term effects of age at surgery on the development of visual acuity (VA) by measuring VA from preschool age to puberty. Furthermore, to report the VA levels at 12 years of age in a geographically based cohort of operated congenital bilateral cataracts. METHODS: All children born in four western counties of Sweden between January 1980 and December 1993 who were diagnosed with congenital cataracts were included in a longitudinal prospective study. The monocular VA of the better eye in 38 subjects was analysed at 4, 7, 10, and 12 years of age, with 20 total and 18 partial cataracts. The mean follow up time was 9.3 years after surgery. RESULTS: The final value of VA was 0.4 or above for approximately 50% of the subjects at 12 years of age. Visual acuity improved to a considerable extent after school age, especially in children who underwent surgery between the ages of 7 weeks and 1 year. Results for partial cataracts were favourable compared to those for total cataracts, reaching a mean of approximately 0.5 at age 12. The mean VA in the group of total congenital cataracts operated on before 7 weeks of age achieved higher values of VA at 4 years of age compared to children with total cataracts operated on between 7 weeks and 1 year of age. However, no statistically significant difference in VA results among these groups could be proved. CONCLUSION: Visual acuity improves to a considerable extent after school age in children with delayed visual development caused by congenital cataracts. Surgery within 7 weeks results in a more rapid development of VA, initially.     

Environmental conditions influence hippocampus-dependent behaviours and brain levels of amyloid precursor protein in rats

Sprague-Dawley rats were reared in enriched (EC; group housing, exposure to stimulating objects, frequent handling) or restricted (RC; individual housing, no exposure to stimulating objects, minimal handling) environments starting on day 23 of life. At six months of age, they underwent behavioural tests to assess 'cognitive' and 'stimulus-response' memory, selective attention, and inflammatory pain processing. Alterations in synapses and cell survival may occur as a result of environment differences; therefore we assessed the brain levels of several proteins implicated in neurite outgrowth, synaptogenesis, and cell survival. Brains were dissected and analysed for amyloid precursor protein (APP) and other synaptic and cytoskeletal proteins using Western blotting. The performance of EC animals in a hidden platform water maze task, and in a test of selective attention (both of which are thought to involve the hippocampus) was superior to that of RC animals. In contrast, performance of RC animals on two stimulus-response tasks, the visible platform water maze test and simple visual discrimination (both of which are thought to be hippocampal independent) was indistinguishable from that of EC animals. Male EC rats displayed a different behavioural response to formalin during the inflammatory phase of nociception--the phase affected by hippocampal processing; a similar trend was observed in females. Female but not male RC rats exhibited elevated plasma corticosterone levels; adrenal weights were unaffected by environmental conditions. Region-specific increases in brain levels of APP, neurofilament-70 (NF-70), and platelet-activating factor receptor (PAF-R) were found in EC rats. These data suggest that enriched animals manifest enhanced functioning of certain hippocampus-mediated behaviours when compared with that of their restricted counterparts; and that brain levels of various synaptic and structural proteins involved in neurite outgrowth, cell survival, and synaptogenesis, are affected by environmental factors.     

Fish consumption and breast cancer risk

The omega-3 fatty acids, especially long-chain eicosapentaenoic acid (20:5n-3) and docosahexaenoic (22:6n-3) contained in "fatty" fish, have consistently been shown to retard the growth of breast cancer in vitro and in animal experiments. In contrast, studies of the association between fish consumption and breast cancer risk in human populations have not consistently shown inverse associations. However, previous studies have not considered the specific types of fish consumed. Using data from a large, nationwide case-control study conducted in Sweden, we examined the association between consumption of fatty and lean fish and breast cancer risk. Odds ratios (OR) and 95% confidence intervals were computed from unconditional logistic regression models. High consumption of fish was weakly associated with reduced breast cancer risk, and the association was not statistically significant. With multivariate adjustment, the OR for women with the highest consumption (> or =3.5 servings/wk) compared with women with the lowest (virtually none) was 0.88 (95% confidence interval = 0.60-1.29, P for trend = 0.15). When type of fish was examined separately, the association was similar for fatty and lean fish.     

Oxidized citrus oil (R-limonene): a frequent skin sensitizer in Europe

BACKGROUND: Peel oil from citrus fruits consists of R-(+)-limonene, which is one of the most commonly used fragrance materials in technical products and in fine fragrances. This substance forms allergenic oxidation products during handling and storage. OBJECTIVE: We wanted to study the frequency of allergic reactions to oxidized R-(+)-limonene in patients with dermatitis and find a suitable test preparation. METHOD: Patch testing with oxidized R-(+)-limonene was performed on 2273 patients at 4 dermatology clinics in Europe. RESULTS: Of the consecutive patients tested, 3.8% to 3.9% had positive reactions in two of the clinics; 6.5% had positive reactions in the third clinic; and 0.3% had positive reactions in the fourth clinic. A total of 63 patients showed positive reactions. In total, 57% of the patients did not react to fragrance mix or balsam of Peru. We recommend testing with 3% oxidized R-(+)-limonene in patients referred for patch testing. CONCLUSION: The high frequency of oxidized limonene allergy provides clinical evidence for the European classification of R-(+)-limonene that contains oxidation products as skin sensitizers.