[Measles, mumps and rubella virus infection in pregnancy. Possible adverse effects on pregnant women, pregnancy outcome and the fetus]. / Masern, Mumps und Röteln in der Schwangerschaft. Mögliche Auswirkungen auf Mutter, Schwangerschaft und Fetus.

Measles, mumps and rubella are common childhood diseases. Therefore, frequent and intense contact with children of preschool age may be associated with a higher infection risk for childcare providers. This overview summarizes current knowledge on possible adverse effects of these infections on pregnant women, pregnancy outcome and the fetus. Acute rubella or mumps virus infections are apparently not more severe in pregnant than non-pregnant women. In contrast, measles virus infection in pregnancy is linked to a higher incidence of pneumonitis and hospitalization. Evidence of congenital defects due to fetal infection is only provided in case of rubella virus infection in early pregnancy. Following rubella virus infection in the first trimester an increased fetal loss rate was reported. In 1966, a prospective study showed also a significant association between maternal mumps in the first trimester and an increased risk of abortion. But other investigators could not confirm this association. Measles and rubella but not mumps virus infections are linked to an increased premature birth rate. Occurring in late pregnancy, all three infections can result in birth of an infected infant. But severe disease occurs rarely and is mostly reported for premature infants with early neonatal measles. Preventive measures, aimed to reduce the risk of infection or severe complications for pregnant childcare providers, should consider the individual history of the employee (e.g. previous immunizations or antibody test results), the current epidemiological situation and possible interventions like passive immunization in case of exposure to measles.

Further studies on the activation of rat median raphe serotonergic neurons by inescapable sound stress.

Previous studies, using a biochemical measure of serotonergic neuronal function, show that inescapable, randomly presented sound pulses activate serotonergic neurons in the rat median raphe but not dorsal raphe nucleus. The present study reveals that this activation also occurs in serotonin projection areas, in hippocampus, nucleus accumbens and cortex but not in caudate nucleus. The selectivity of this response is examined by comparing the response to sound stress with that produced by morphine, a treatment known to selectively activate dorsal raphe but not median raphe serotonergic neurons. Two approaches are used in Sprague-Dawley rat to measure the activation of serotonergic neurons: (1) determination ex vivo of accumulation of 5-hydroxytryptophan (5-HTP) in tissue from the dorsal and median raphe nuclei, hippocampus, cortex, caudate nucleus, and nucleus accumbens following in vivo inhibition of aromatic amino acid decarboxylase; and (2) measurement of extracellular serotonin levels in hippocampus, caudate nucleus, and nucleus accumbens. Sound stress increases 5-HTP accumulation in median raphe nucleus, hippocampus, cortex, and nucleus accumbens, but not dorsal raphe nucleus or caudate nucleus. Sound stress also enhances extracellular serotonin levels in hippocampus and nucleus accumbens, but not caudate nucleus. In contrast, the morphine treatment enhances 5-HTP accumulation in dorsal raphe nucleus, cortex and caudate nucleus, but not in median raphe nucleus, hippocampus or nucleus accumbens. Furthermore, it increases extracellular serotonin levels in only the caudate nucleus. The combined effects of sound stress and morphine on 5-HTP accumulation are identical to those obtained by each treatment individually. These findings provide further support for the presence of serotonergic neurons within the median raphe nucleus that have a unique response profile. These neurons may have an important role in responses or adaptations to stress.

Mutations in the X-linked filamin 1 gene cause periventricular nodular heterotopia in males as well as in females.

Periventricular heterotopia (PH) is a human neuronal migration disorder in which many neurons destined for the cerebral cortex fail to migrate. Previous analysis showed heterozygous mutations in the X-linked gene filamin 1 (FLN1), but examined only the first six (of 48) coding exons of the gene and hence did not assess the incidence and functional consequences of FLN1 mutations. Here we perform single-strand conformation polymorphism (SSCP) analysis of FLN1 throughout its entire coding region in six PH pedigrees, 31 sporadic female PH patients and 24 sporadic male PH patients. We detected FLN1 mutations by SSCP in 83% of PH pedigrees and 19% of sporadic females with PH. Moreover, no PH females (0/7 tested) with atypical radiographic features showed FLN1 mutations, suggesting that other genes may cause atypical PH. Surprisingly, 2/24 males analyzed with PH (9%) also carried FLN1 mutations. Whereas FLN1 mutations in PH pedigrees caused severe predicted loss of FLN1 protein function, both male FLN1 mutations were consistent with partial loss of function of the protein. Moreover, sporadic female FLN1 mutations associated with PH appear to cause either severe or partial loss of function. Neither male could be shown to be mosaic for the FLN1 mutation in peripheral blood lymphocytes, suggesting that some neurons in the intact cortex of PH males may be mutant for FLN1 but migrate adequately. These results demonstrate the sensitivity and specificity of DNA testing for FLN1 mutations and have important functional implications for models of FLN1 protein function in neuronal migration.

Neurotensin inhibits the activation of midbrain serotonergic neurons produced by random inescapable sound.

Previous studies indicate that exposure of rats to randomly presented, inescapable loud sound, referred to as sound stress, increases central serotonin turnover as well as the ex vivo activity of tryptophan hydroxylase (EC 1.14.16.4), the rate-limiting enzyme in serotonin biosynthesis. The purpose of this investigation was to determine whether intracerebroventricular (i.c.v.) administration of neurotensin (NT), a tridecapeptide found within the midbrain raphe, influences the activation of the midbrain serotonergic neurons by sound stress. Accumulation of 5-hydroxytryptophan (5-HTP) in vivo, in the presence of the aromatic amino acid decarboxylase inhibitor, NSD 1015 (m-hydroxybenzylhydrazine, 100 mg/kg i.p.) given immediately before a 30 min sound stress, was used as an index of in vivo tryptophan hydroxylase activity. Sound-stressed rats had significantly higher levels of 5-HTP in cortex and midbrain compared to sham-stressed controls. NT (0.01-3.3 nmol total), given i.c.v., 5 min prior to 30 min sound stress, completely blocked the enhanced accumulation of 5-HTP, but had no effect on basal accumulation of 5-HTP, except at the highest doses of 1.0 or 3.3 nmol, which others have previously shown to inhibit basal serotonergic metabolism. NT (0.3 and 3.3 nmol) blocked the increase in cortical tryptophan hydroxylase activity, ex vivo, in response to 30 min sound stress, without affecting basal enzyme activity. These and other recent data suggest a possible role for endogenous NT in the regulation of serotonergic neuronal activity within the midbrain raphe.

Differential activation of the 5-hydroxytryptamine-containing neurons of the midbrain raphe of the rat in response to randomly presented inescapable sound.

Estimates of 5-hydroxytryptamine (5-HT) turnover in response to 30 min of inescapable, randomly presented, loud sound (sound stress) were obtained for regions of rat brain containing 5-HT perikarya by means of 5-hydroxytryptophan (5-HTP) accumulation after administration of an inhibitor of aromatic amino acid decarboxylase (100 mg/kg i.p., m-hydroxybenzylhydrazine, NSD 1015). Sound stress increased 5-HTP accumulation in the median raphe nucleus (MRN) twofold over that from sham-stressed controls, but did not change 5-HTP accumulation significantly in dorsal raphe nucleus (DRN) or hindbrain. These findings indicate that the 5-HT perikarya of the MRN but not those of the DRN or hindbrain are activated by sound stress, thus, provide further evidence for a functional distinction between the 5-HT neurons of these two midbrain nuclei.

Intracranial dehydroepiandrosterone blocks the activation of tryptophan hydroxylase in response to acute sound stress.

Bilateral infusion of dehydroepiandrosterone (DHEA) given intracerebroventricularly blocked the sound stress-induced increase in tryptophan hydroxylase activity observed ex vivo in midbrain and cortex but had no effect on the level of tryptophan hydroxylase activity from sham-stressed rats. DHEA (20 micrograms total dose) given bilaterally into the region of the central nucleus of the amygdala, 30 min prior to 1 h sound stress, also blocked the increase in enzyme activity in a dose-dependent manner. The DHEA treatment did not alter the activation of the enzyme seen in vitro in the presence of phosphorylating conditions. The effect of DHEA was steroid specific in that other sex steroids, such as estrogen, androgens, or progesterone, were without any effect. Coadministration, 20 micrograms each, of the potent glucocorticoid agonist, RU 28362, with DHEA 30 min prior to 1 h sound stress completely blocked the DHEA suppressive effect on sound stress-induced increases in tryptophan hydroxylase activity. The results obtained suggest that DHEA blocks this increase in tryptophan hydroxylase activity by antagonizing the effects of glucocorticoid.

Sound stress activation of tryptophan hydroxylase blocked by hypophysectomy and intracranial RU 38486.

The rapidly reversible increase in cortical or midbrain tryptophan hydroxylase activity observed ex vivo after exposure of rats to 1-h sound stress was blocked by hypophysectomy, but not sham hypophysectomy, and restored by dexamethasone administration to the hypophysectomized animals (500 micrograms/day i.p. for 3 days). The response to sound stress was also lost with deafferentation of the hypothalamus. These results indicate that hypothalamic control of adrenal glucocorticoids is required for the serotonergic response to sound stress. The glucocorticoid antagonist, RU 38486, given intracerebroventricularly (200 micrograms/day for 4-5 days) or bilaterally, into the region of the central nucleus of the amygdala (100 micrograms 15 min before stress), blocked the sound stress-induced increase in tryptophan hydroxylase activity. In contrast, the antimineralocorticoid, RU 26752, was without effect. The block obtained with RU 38486 suggests that glucocorticoid is required by the neurons that relay the effects of sound stress to the rostrally projecting serotonergic neurons.

Evidence that corticotropin-releasing factor within the extended amygdala mediates the activation of tryptophan hydroxylase produced by sound stress in the rat.

Non-endocrine corticotropin-releasing factor (CRF) is believed to be involved in mediating stress behaviors in rats. The present study investigated the role of CRF in mediating the activation of tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, produced in response to sound stress. Bilateral injections of 0.5-3.0 micrograms of CRF directed towards the central nucleus of the amygdala increased tryptophan hydroxylase activity measured ex vivo when compared to vehicle-injected controls. This increase in enzyme activity, like that due to sound stress, was reversed in vitro by alkaline phosphatase. Intra-amygdala CRF (0.5 microgram) also enhanced the in vivo accumulation of 5-hydroxytryptophan (5-HTP) following the administration of m-hydroxylbenzylamine (NSD-1015, 200 mg/kg). The activation of tryptophan hydroxylase, produced by intra-amygdala CRF, was blocked by the CRF receptor antagonist alpha-helical CRF9-41 (10 micrograms). Additionally, the 5-HT1A agonist, gepirone, given either systemically (10 mg/kg) or intracerebrally into the region of the dorsal raphe (14 micrograms), blocked the tryptophan hydroxylase response to CRF. CRF did not increase tissue levels of 5-hydroxyindole acetic acid (5-HIAA) or the ratio of 5-HIAA to serotonin (5-HT) within the striatum of the same animals in which tryptophan hydroxylase activity was quantified, an effect produced by sound stress. Thus, while intra-amygdala CRF failed to mimic the sound stress response in its entirety, these data suggest that CRF is involved in mediating the activation of tryptophan hydroxylase produced by sound stress within the midbrain serotonin neurons.

Constituent syllable effects in a nonsense-word repetition task.

Multisyllabic nonsense-word repetition tasks have been used to provide evidence on the phonological processing operations of children with language impairment, independent of their lexical knowledge (Gathercole & Baddeley, 1990; Kamhi, Catts, Mauer, Apel, & Gentry, 1988). However, recent evidence (Gathercole, Willis, Emslie, & Baddeley, 1991) and speculation (Snowling, Chiat, & Hulme, 1991) suggest that the nonsense words employed in such tasks may not be equally "nonsensical." The present investigation directly tested the effect on repetition performance of one previously uncontrolled characteristic of multisyllabic nonsense words: the lexical status (word or nonword) of their stressed syllables. Normally achieving school-age boys repeated nonsense words with lexical stressed syllables significantly more accurately than nonsense words with nonlexical stressed syllables. These results suggest the need to control, at a minimum, the lexical status of constituent syllables in constructing nonsense-word stimuli.

Effect of gepirone on increases in tryptophan hydroxylase in response to sound stress.

Pretreatment (15 min) of male rats with gepirone given parenterally (10 mg/kg i.p.) or intracranially into the dorsal raphe nucleus (14 or 21 micrograms) blocks the rapidly reversible increase in brain tryptophan hydroxylase activity and 5-hydroxyindolamine acetic acid tissue levels seen in vitro after 1-h acute sound stress. Chronic gepirone treatment over 28 days (40 mg/day s.c.) prevents the stable enzyme activity increase induced by repeated sessions of sound stress, and the rapidly reversible increase always observed following sound stress. The gepirone metabolite, 1-(2-pyrimidinyl)-1-piperazine, is inactive in each of these experiments. Transient blood pressure elevations occur with each sound presentation, but no persistent hypertension is observed with repeated sound-stress exposures. Gepirone may block the sound stress-induced biochemical increases by its inhibition of serotonergic neuronal firing in the dorsal raphe nucleus that is mediated by its agonist action at the somatodendritic (5-HT1A) autoreceptors.

Increase in cortical and midbrain tryptophan hydroxylase activity by intracerebroventricular administration of corticotropin releasing factor: block by adrenalectomy, by RU 38486 and by bilateral lesions to the central nucleus of the amygdala.

Corticotropin releasing factor (CRF) infused bilaterally into the lateral ventricles of awake, chronically cannulated, male Sprague-Dawley rats produced a dose-dependent increase in the in vitro activity of cortical and midbrain tryptophan hydroxylase after 60 min. The maximal increase in enzyme activity of 60% over that of vehicle-treated controls was reached 45 min after an infusion of 3 micrograms CRF. The increase in enzyme activity after a single dose of CRF resembled that seen after exposure of rats to an acute sound stress: it was reversed by preincubation of the enzyme preparation with alkaline phosphatase and was nonadditive with the increase in activity obtained in the presence of phosphorylating conditions. The response to intracerebroventricularly administered CRF was abolished by bilateral adrenalectomy, but restored by repeated daily systemic administration of the synthetic glucocorticoid, dexamethasone (500 micrograms/day, i.p. for 3 days), to the adrenalectomized rats. Intracerebroventricular administration of the glucocorticoid antagonist, RU 38486 (200 micrograms/day for 4 days), also blocked the acute increase in tryptophan hydroxylase activity in response to CRF. Finally, bilateral lesions to the central nucleus of the amygdala, a region involved in mediating behavioral, endocrine and autonomic responses to stressful stimuli, abolished the increase in enzyme activity in response to intraventricular CRF. The glucocorticoid sensitivity of the response to CRF, as well as the involvement of the central nucleus of the amygdala support the view that CRF may have a role in mediating the enhancement of tryptophan hydroxylase activity by acute sound stress.

The increases in rat cortical and midbrain tryptophan hydroxylase activity in response to acute or repeated sound stress are blocked by bilateral lesions to the central nucleus of the amygdala.

Sound stress (SS) (120-dB pulses of 100 ms duration, every min for 1 h) produces an elevation of in vitro cortical or midbrain tryptophan hydroxylase activity from male Sprague-Dawley rats that is abolished, in vitro, by incubation of the enzyme preparation with alkaline phosphatase. SS, when repeated on 3 different occasions, the first 2 sessions 24 h apart and the 2nd and 3rd session separated by 48 h, produces a stable increase in the in vitro enzyme activity that is unaffected by alkaline phosphatase. Bilateral lesions to the central nucleus of the amygdala block both increases in enzyme activity obtained in response to acute and repeated SS, but leave enzyme activity from sham-stressed rats unaffected.

Parvovirus B19 infections in pregnancy.

Since 1986, 2,279 pregnant women were screened for anti Parvovirus B19 IgG and IgM antibodies. Of them 41% were seronegative, 54% had specific IgG but no IgM antibodies, indicating an infection in earlier life. Acute infection could be demonstrated by IgM antibody detection in 114 pregnant women (32% in the first, 54% in the second and 14% in the third trimester). Hydrops fetalis occurred in 10 of the 114 pregnancies (8.7%). In five of these cases intrauterine exchange transfusion was done and until now four healthy babies were born. Three fetuses died and one pregnancy was terminated, and two pregnancies are not yet completed. Fetal loss occurred in 9 of the 114 pregnancies (7.8%) (three fetal deaths after hydrops fetalis in the second trimenon and six spontaneous abortions in the first trimenon). In 51 of the 70 pregnancies which came thus far to term clinical data were available from the newborns. All these children were healthy at birth and later. In 22 of the 51 newborns, serological investigation was possible. In only two of them evidence of prenatal infection was detectable.

Increases in the activity of tryptophan hydroxylase from rat cortex and midbrain in response to acute or repeated sound stress are blocked by adrenalectomy and restored by dexamethasone treatment.

Exposure of male Sprague-Dawley rats to acute sound stress (2 s, 110 dB sound pulses presented randomly every minute for 1 h) increases the in vitro activity of cortical and midbrain tryptophan hydroxylase by an alkaline phosphatase-reversible mechanism. Repeated exposure to sound stress on three separate days produces a stable increase in enzyme activity that persists 24 h after the termination of the stress and is insensitive to alkaline phosphatase. Adrenalectomy abolishes both increases in enzyme activity to acute or repeated sound stress but does not change baseline levels of enzyme activity. The synthetic glucocorticoid, dexamethasone, (500 micrograms/day i.p.) given for 3 days or 5 out of 6 days, starting day 3 after adrenalectomy, restores the increases in enzyme activity in adrenalectomized rats exposed, respectively, to acute or repeated sound stress. The mineralocorticoid, aldosterone (5 micrograms/day s.c.), does not substitute for dexamethasone in acutely sound-stressed, adrenalectomized rats. Dexamethasone does not alter control levels of enzyme activity in either adrenalectomized rats or rats with intact adrenals (sham-adrenalectomized), but is required to allow the increase in enzyme activity in response to acute or repeated sound stress to be expressed. The effect of the glucocorticoid, thus, appears to be a permissive one.

Lyme polyradiculoneuropathy presenting as increasing abdominal girth.

We describe a patient with documented Lyme disease whose major complaint was increasing abdominal distention. Electrophysiologic studies demonstrated denervation of the lower thoracic paraspinal muscles and the rectus abdominis. Expanding abdominal girth can be an unusual manifestation of the polyradiculoneuropathy associated with Lyme disease.

Prevalence of antibodies to human herpesvirus 6 in different age groups, in children with exanthema subitum, other acute exanthematous childhood diseases, Kawasaki syndrome, and acute infections with other herpesviruses and HIV.

We determined IgG antibodies against Human Herpesvirus-6 (strain Uganda 1102, M. D. Griffin, London) in the indirect immunofluorescence test in sera from 1105 persons of various age groups. Of these sera 570 were retested using HHV-6 strain St. W. (Prof. Schneweis, Bonn). We could confirm that maternal antibodies decrease between birth and six months of age and the seropositive rate rises rapidly between seven months and five years of age up to 79.5%. Between six and ten years and up to 40 years, the antibody-positive rate lies around 81.3% and 66%, respectively. To confirm the causal nature of human herpes virus type 6 (HHV-6) for exanthema subitum we could demonstrate eight seroconversions testing sera from 14 patients with roseola infantum. In addition, the virus was isolated from peripheral blood lymphocytes of children during the acute fever phase in four cases in tissue culture and in six cases the virus was detected by positive hybridization. In single and some paired sera from patients with acute exanthematous diseases, rubella (n = 28), parvovirus B 19 (n = 24), measles (n = 17), mumps (n = 27), adenovirus (n = 27) and parinfluenza virus type 3 (n = 28) and in sera from patients with Kawasaki syndrome (n = 20), acute varicella-zoster- (n = 27), acute herpes simplex- (n = 18) and HIV-1 infection (n = 50), we found no HHV-6 IgM antibodies and no HHV-6 IgG antibody rises. We could only demonstrate an HHV-6 seropositive rate according to our age-prevalence study.(ABSTRACT TRUNCATED AT 250 WORDS)

Hunger pain: a poor indicator of peptic ulcer in a developing country.

Endoscopy of the esophagus, stomach, and duodenum and stool examinations for ova and parasites were performed in 63 adult Peruvian patients with "hunger pain" (HP) and other dyspeptic symptoms. No lesion capable of provoking HP was found at endoscopy in 50 (78%) of the 63 patients. Only 7 (12%) of the patients had evidence of active or healed peptic ulcers. Another 6 patients (10%) had either gastric erosions or duodenitis. One (2%) of the patients was infected with hookworm, a parasite that produces epigastric pain mimicking HP. The 12% rate of peptic ulcer in Peruvian patients with HP contrasts strongly with accumulated experience in most developed countries, whose rates of peptic ulcer associated with HP range from 60 to 75%. As the frequency of peptic ulcer is so variable in patients with HP, we suggest that the simple term "hunger pain" be used instead of "peptic ulcer pain" or "ulcer dyspepsia" to refer to the complaint of such patients.

Blockade of morphine-induced increases in brain tryptophan hydroxylase activity by systemic pretreatment with CCK-8: no reversal by vagotomy.

The treatment of rats with CCK-8 suppresses the behavioral responses to subsequent injection of opiates. We have investigated the possibility that peripherally administered CCK-8 can also suppress a neurochemical response to opiates, namely the increase in brain tryptophan hydroxylase (TrpH) activity and tissue 5-hydroxyindole acetic acid (5-HIAA) which results from morphine administration. While morphine sulfate (4 mg/kg s.c.) roughly doubled brain TrpH activity and tissue 5-HIAA 40 min after injection, pretreatment with CCK-8 (5 micrograms/kg i.p., 10 min prior to morphine) completely abolished this neurochemical change induced by morphine. Doses of CCK-8 as low as 1 microgram/kg were effective in blunting the morphine-induced increase in cortical TrpH activity, but the desulfated form was ineffective at doses of 5 and 100 micrograms/kg. Subdiaphragmatic vagotomy did not prevent the effect of CCK-8.