Postnatally acquired cytomegalovirus infection via breast milk: effects on hearing and development in preterm infants

BACKGROUND: In preterm infants there is a high risk of transmission of cytomegalovirus (CMV) via breast milk from seropositive mothers with reactivation of the virus during lactation. There is little information about the long term sequel of early postnatally acquired CMV infection in pre-term infants. This study aimed to investigate whether there was an increased frequency of impaired neurodevelopmental outcome and sensorineural hearing loss in preterm infants with postnatally acquired CMV infection through transmission by CMV-positive breast milk. METHODS: Twenty-two preterm infants [median birth weight, 1020 g (range, 600 to 1870 g); median gestational age, 27.6 weeks (range, 23.6 to 32 weeks] with early postnatally acquired CMV infection by breast-feeding (onset of viruria between Days 23 and 190 postnatally) were compared with 22 CMV-negative preterm infants individually matched for gestational age, birth weight, gender, intracranial hemorrhage and duration of ventilation. At 2 to 4.5 years of age, follow-up assessments were conducted consisting of neurologic examination, neurodevelopmental assessment and detailed audiologic tests. RESULTS: None of the children had sensorineural hearing loss. There was no difference between the groups with regard to neurologic, speech and language or motor development. CONCLUSION: The results of this study suggest that early postnatally acquired CMV infection via CMV-positive breast milk does not have a negative effect on neurodevelopment and hearing in this group of patients. Because we studied a small number of infants, further follow-up studies are warranted in preterm infants with early postnatally acquired CMV infection.     

Centrally administered oxytocin elicits exaggerated grooming in oxytocin null mice

Experiments were conducted to determine if the chronic absence of the neurotransmitter oxytocin (OT) in null mice resulted in alterations in the responsiveness and abundance of central OT receptors. Self-grooming elicited by intracerebroventricularly administered OT was studied as an indicator of the activation of central OT receptors and autoradiography was used to map the distribution and density of OT receptors in OT null and wild type mice. The intracerebroventricular administration of OT, but not vehicle, artificial cerebrospinal fluid (aCSF), produced a robust increase in grooming behavior in both OT null and wild type animals, P<.001. However, OT-induced grooming was significantly greater in OT null than wild type mice, P<.005. The enhanced grooming was selective to OT as indicated by the finding that grooming to intracerebroventricular arginine vasopressin (AVP) was of the same magnitude in both OT null and wild type mice. OT-induced grooming appears to be mediated through the activation of OT receptors because pretreatment of animals with an OT antagonist, Atosiban, abolished OT-induced grooming, but not AVP-induced grooming. OT receptor distribution and binding in brains of OT null and wild type mice were examined by autoradiography and were not significantly different. The results indicate that the chronic absence of OT in null mice leads to an increase in OT receptor responsiveness that contributes to the augmented grooming activity elicited by centrally administered OT.     

Fenfluramine-induced hypothermia is associated with cutaneous dilation in conscious rats

The antiobesity agent, fenfluramine, produces hypothermia in rodents by an, as yet, uncharacterized mechanism. The present study was conducted in conscious rats to determine if fenfluramine-induced hypothermia was associated with cutaneous dilation. In animals maintained at 16 degrees C, core body temperature (T(CORE)) was measured telemetrically, and tail surface temperature was monitored with thermocouples fixed to the tail (T(TAIL)). D-Fenfluramine (10 mg/kg ip) produced a rapid increase in T(TAIL) of 7.7+/-0.4 degrees C (P<.001) and a decline in T(CORE) of 4+/-0.3 degrees C (P<.001). Two findings indicate that the increase in T(TAIL) was due to the withdrawal of a sympathetic vasoconstrictor tone. First, pretreatment with the ganglionic blocker, pentolinium, prevented fenfluramine-induced changes in T(TAIL). Second, when sympathetic tone to the tail was physiologically withdrawn by increasing the environmental temperature to 28 degrees C, fenfluramine treatment produced no increase in T(TAIL). Moreover, the effects of fenfluramine on T(TAIL) and T(CORE) depended on the uptake of fenfluramine into serotonergic neurons because these effects were markedly attenuated by pretreatment with the selective serotonin re-uptake inhibitor, fluoxetine. The hypothermic effect of fenfluramine occurred despite the fact that total body oxygen consumption increased by 20%. The results suggest that heat loss due to the dilation of the cutaneous circulation contributes to fenfluramine-induced hypothermia.     

Sexuality in patients with amyotrophic lateral sclerosis and their partners

Abstract. Sexuality in patients with amyotrophic lateral sclerosis (ALS) has received little attention so far. Although sexual function is not directly affected by the disease process, several patients have reported problems within their sexual relationship. We performed a questionnaire survey to ascertain the extent and clinical relevance of sexual problems experienced by patients with ALS and their partners. Of 91 patients and partners asked, 62 agreed to participate in the study. Compared with the time before disease onset, sexual interest had decreased from 72 % to 44% for patients and from 78 % to 44% for partners. Sexual activity had moderately decreased from 94 % to 76% for the patients and from 100% to 79 % for the partners. Before the disease, 19% of the patients and 20% of the partners reported sexual problems. This increased to 62% of the patients and 75% of the partners at time of survey. The problems reported were mainly decreased libido, passivity of the partner and own passivity. The most frequent reasons for these problems were the physical weakness and the body image changes due to ALS. The data show that sexuality is an important and problematic issue for a large proportion of ALS patients and their partners. This topic is rarely discussed in the medical setting. Counselling and information should be made available in order to better address this important aspect of quality of life.     

Prevalence and treatment of spasticity reported by multiple sclerosis patients

The objective of this study was to characterize the population of multiple sclerosis (MS) patients suffering from spasticity and to evaluate treatment patterns, including intrathecal baclofen (ITB) delivery, related to patient quality of life (QOL). We conducted a cross-sectional, two-level study using data from the Patient Registry of the North American Research Committee on MS (NARCOMS). In addition, we surveyed a subgroup of 198 preselected patients who are using ITB (ITBG) and a random sample of 315 oral drug users (ORALG). Among the registrants, 16% reported no spasticity, 31% minimal, 19% mild, 17% moderate (frequently affects activities), 13% severe (daily forced to modify activities) and 4% total (prevents daily activities). Patients experiencing greater severity included by proportion males, and those older and with longer duration of MS. QOL scores decreased inversely with severity. In the focused survey, ITBG reported lower levels of spasticity than ORALG, less stiffness in the legs, less pain and fewer spasms at any time. They scored significantly lower in the SF-36 physical component, yet reported less fatigue on the MFIS scale. Prevalence data reveal that one third of MS patients modify or eliminate daily activities as a result of spasticity. Treatment of spasticity can significantly impact QOL parameters by reducing spasms, pain and fatigue.     

Comparative responses of three rat strains (DA/Han,Sprague-Dawley and Wistar) to treatment with environmental estrogens

The rat uterotrophic assay is a widely used screening test for the detection of estrogenic, endocrine-disrupting chemicals. Although much attention has been paid to identifying protocol variables and reproducibility between laboratories the question whether toxicodynamic and toxicokinetic variations of different strains may affect their sensitivity to estrogenic stimuli has been rarely addressed. We have compared the estrogenic activity of the environmental chemicals genistein (GEN), bisphenol A (BPA) and p-tert-octylphenol (OCT) in DA/Han (DA), Sprague-Dawley (SD) and Wistar (WIS) rats after repeated oral application. Rats were treated per os for 3 days with different doses of these weakly estrogenic compounds and the potent reference estrogen ethinylestradiol (EE). Then uterine wet weight, thickness of the uterine epithelium, uterine gene expression of clusterin (CLU), and thickness of the vaginal epithelium were examined as parameters for estrogenic potency of the test compounds in the three strains of rats. The uterotrophic response to treatment with BPA, OCT and GEN was similar in the three strains, and allowed us to rank them as GEN being more potent than OCT, and BPA being the weakest estrogen. This was confirmed by analysis of other biological endpoints, despite some differences in the magnitude of their response among strains and to distinct compounds. For instance, the uterus wet weight response to EE treatment indicated lower sensitivity of SD rats than that of DA and WIS rats, but this was not observed for responses of the uterine or vaginal epithelium. Moreover, blood concentrations were assessed at the time of killing and related to biological responses: plasma levels of total and unconjugated BPA and GEN depended upon the dose administered and varied to some extent within treatment groups and among the three rat strains. However, there was no good correlation in the three strains between individual compound concentrations analysed 24 h after the last dose and the uterotrophic wet weights. Summarising our results, we conclude that the sensitivity of various biological endpoints can differ slightly between strains of rats. On the other hand, our data demonstrate that the choice of the rat strain does not lead to pronounced differences in the evaluation of estrogenic activities of chemicals, especially when different biological endpoints are included in the analysis.     

Regulation of gene expression by 8-prenylnaringenin in uterus and liver of Wistar rats

The potential estrogenic activity of 8-prenylnaringenin has been investigated using several in vitro test systems. 8-Prenylnaringenin is a natural secondary product of the female blossoms of hops. The aim of the present study was to characterize 8-prenylnaringenin for its estrogenic effects in vivo. A three day uterotrophic assay was carried out on ovariectomized young female rats. A single dose of 8-prenylnaringenin (10 mg/day/kg body mass) was administered subcutaneously. 17beta-Estradiol (0.03 mg/day/kg body mass; subcutaneous administration) was used as a positive control. Uterine wet weight, endometrial and vaginal epithelial height were determined by histological methods. Gene expression in uterus and in liver was assessed using realtime RT-PCR. Both estradiol and 8-prenylnaringenin significantly stimulated uterine wet weight accompanied by a proliferative response. The three day treatment resulted in a statistically significant increase of the uterine epithelial height as well as of the vaginal epithelial height, the latter being the more sensitive parameter. In the uterus of ovariectomized animals estrogen receptor-alpha and clusterin gene expression were down regulated following treatment with estradiol, whereas expression of complement C3 was up-regulated. In response to treatment with 8-prenylnaringenin the same gene expression pattern was detectable, but less pronounced. The levels of estrogen receptor-alpha mRNA in rat liver were very low and therefore could not be quantitatively assessed. Like in the uterine tissue, estradiol down regulated clusterin expression. The response to 8-prenylnaringenin was weaker but still significant. Conversely, 8-prenylnaringenin was found to be more potent than estradiol in inducing expression of IGFBP-1. In summary, the multiparametric assessment of the estrogenic activity of 8-prenylnaringenin provides overwhelming evidence that 8-prenylnaringenin has largely to be regarded as a pure estrogen agonist and is therefore a questionable candidate molecule for hormone replacement therapy.