Emerging and re-emerging infectious disease in otorhinolaryngology.

SUMMARY: Emerging and re-emerging infectious disease in otorhinolaryngology (ENT) are an area of growing epidemiological and clinical interest. The aim of this section is to comprehensively report on the epidemiology of key infectious disease in otorhinolaryngology, reporting on their burden at the national and international level, expanding of the need of promoting and implementing preventive interventions, and the rationale of applying evidence-based, effective and cost- effective diagnostic, curative and preventive approaches. In particular, we focus on i) ENT viral infections (HIV, Epstein-Barr virus, Human Papilloma virus), retrieving the available evidence on their oncogenic potential; ii) typical and atypical mycobacteria infections; iii) non-specific granulomatous lymphadenopathy; iv) emerging paediatric ENT infectious diseases and the prevention of their complications; v) the growing burden of antimicrobial resistance in ENT and the strategies for its control in different clinical settings. We conclude by outlining knowledge gaps and action needed in ENT infectious diseases research and clinical practice and we make references to economic analysis in the field of ENT infectious diseases prevention and care.

Effects of acoustic stimulus duration on cervical vestibular evoked myogenic potentials: A neurophysiological and modeling study.

OBJECTIVE: To analyze and model the effects of acoustic stimulus duration on cervical vestibular evoked myogenic potentials (cVEMPs). DESIGN: Subjects with normal hearing and no vestibular or cervical disorders were tested using 1 kHz tone bursts (TBs) of different durations to evoke cVEMPs from the ipsilateral sternocleidomastoid muscle. VEMP modeling was performed in Labview. RESULTS: The increase in TB duration initially resulted in a non-linear increase in cVEMP amplitude, followed by more complex cVEMP modifications that were mainly related to the appearance of a new wave (nX) that interfered with n23. With long TBs there were two distinct negative peaks with an identical threshold, suggesting a common vestibular nature. A two-level inhibition model qualitatively accounted for the two distinct negative peaks. However, good fitting of the cVEMP waveform required a multi-level model that included an excitatory phase after the inhibitory period. CONCLUSIONS: The two negative components (n23 and nX) observed in cVEMPs elicited by long TBs may result from the involvement of two different pathways with different dynamics or a single pathway with quick adaptation in the activity along the vestibulo-collic arc. Excitatory activity following the period of inhibition may represent rebound activity at the motor unit level.

The reversed ipsilateral acoustic reflex: clinical features and kinetic analysis.

OBJECTIVE: The reversed ipsilateral acoustic reflex (RIAR) has been the subject of few studies in the past literature and the nature of this "reflex" response is not yet completely understood. It can be observed in different diseases, all of which result from inactivity of the stapedial reflex (SR). We aimed to investigate the occurrence of the RIAR in different diseases. MATERIAL AND METHODS: An extensive clinical investigation of the RIAR was carried out. RESULTS: The RIAR was found to be present in 100% of ears lacking an effective SR arc. Its amplitude is modulated by the air pressure level in the external ear canal whilst its sign is constantly positive and never reverses. CONCLUSION: Kinetic analysis of the RIAR suggests the existence of a single underlying phenomenon while the interaction of the RIAR with the SR may explain the complex morphology frequently observed in the normal ipsilateral acoustic reflex.

[Bacterial vaginosis and pregnancy]. / Vaginosi batterica e gravidanza.

Premature rupture of membranes (PROM) occurs in approximately 5-10% of all pregnancies and is implicated in approximately one third of preterm births. PROM is associated with increased risks of perinatal as well as maternal morbidity and mortality at every gestational age. Much information suggest that the presence of bacterial vaginosis may be implicated in the occurrence of PROM and subsequent preterm delivery in significant numbers of pregnant women. We will briefly review clinical and pathophysiologic information linking bacterial vaginosis and PROM.

[Prognosis and treatment of cervix uteri carcinoma in pregnancy]. / Prognosi e trattamento del carcinoma della cervice uterina in gravidanza.

Carcinoma of the cervix is tha most common ginecologic cancer found during pregnancy. Management and treatment of this condition depend on cancer stage and estimated gestational age. Pregnancy represents an ideal time for cervical cancer screening, and all pregnant women presenting for prenatal care should be carefully examinated. The prognosis for pregnant women is similar to that for non-pregnant one. The aim of this study is to review the incidence, treatment and prognosis of this condition during pregnancy.

[Asymptomatic bacteriuria in pregnancy]. / Batteriuria asintomatica in gravidanza.

Pregnancy is a predisposing factor for urinary tract infection and pregnant women suffering from this pathology are exposed to dangerous risks which may condition maternal wellbeing and fetal prognosis. Asymptomatic bacteriuria is the common bacterial infection requiring medical treatment in pregnancy. Diagnosis and treatment of asymptomatic bacteriuria is important as approximately 20-40% of these women, if untreated during pregnancy, will develop a symptomatic urinary tract infection.

[Etiology and epidemiology of extrauterine pregnancy]. / Eziologia ed epidemiologia della gravidanza extrauterina.

In the last years, ectopic pregnancy has become a frequent problem, especially in the industrialized countries. Women aged 30-40 years are mostly affected. Infact, in this ten-years period, more and more women feel the desire of pregnancy at ripe age, first of all because of their job. This study shows 136 cases of extrauterine pregnancy, observed at our hospital, I and II Institute of Obstetric and Gynecological Clinic of "Policlinico Umberto I" in Rome from January 1997 to December 1999. The object of this analysis is to determine the characteristics and ethiologic factors of this pathology.

[A case of maternal and neonatal infection due to Listeria monocytogenes]. / Caso d'infezione materna e neonatale provocata da Listeria monocytogenes.

A Listeria monocytogenes infection may develop during pregnancy by eating sausages, fresh meats and milk products derived from infected animals. According to the period in which the infection starts, the pregnancy outcome can be abortion or pre-term or at term delivery. The infection can pass from mother to fetus and can cause a serious neonatal sepsis. Listeriosis in pregnant women can be asymptomatic or may present as an influenza-like syndrome. This case report, along with other published cases, demonstrates how hard is to make a correct diagnosis of listeriosis during pregnancy. Since this is mainly related to the aspecificity of symptoms, it is very important to have a high suspicion and to take a careful patient history.

[Use of GnGH (GnRH-A) in gynecology]. / Uso degli analoghi del GnRH (GnRH-A) in ginecologia.

GnRH-agonist therapy is used in the management of many gynaecological pathologies: uterine fibroids, endometriosis, ovarian cystic pathology, breast cancer, dysfunctional uterine bleeding and, in males, prostatic cancer. In the case of uterine fibroids, this therapy can be used as a pre-treatment before conservative or demolitive surgery or as an alternative to hysterectomy. At the Centre for Therapy of Uterine Pathologies (I Institute of Obstetrics and Gynaecology of the University of Rome "La Sapienza") the use of Gn-RH-A therapy in uterine fibroids has been investigated and results consistent with those of many other groups of study have been obtained. The two most important results are: 1. the decrease of both the myoma's size and the uterine volume; 2. the block of menometrorrhagiae symptoms, with improvement of the haematic crasis and possibility to convert a demolitive surgery to a conservative surgery. GnRH-agonists can represent a definitive treatment for patients with symptomatic uterine fibroids and in perimenopausal age.

[The role of the pineal body in the endocrine control of puberty]. / Il ruolo della pineale nel controllo endocrino della pubertà.

The pineal gland plays an important role in reproductive endocrinology. The epiphysis regulates seasonal variations in reproductive function of seasonally breeding animals. In humans, even if they are not seasonal breeders, the role of the pineal in reproductive endocrinology seems to be important as well. It appears to be of particular importance the endocrine control of the gland on pubertal sexual maturation. Even if not all researchers agree, several data suggest that elevated melatonin levels-characteristic of prepubertal age-keep the hypothalamic-pituitary-gonadal axis in quiescence: thus, an inhibitory effect on pubertal development is exerted. Subsequently, the decreasing serum melatonin with advancing age would result in activation of the hypothalamic pulsatile secretion of GnRH- and therefore of the reproductive axis-with consequent onset of pubertal phenomena. The production rate of melatonin does not change with age and no growth in pineal size from 1 to 15 years of age has been demonstrated by nuclear magnetic resonance (NMR) studies. Therefore the decrease of serum melatonin concentrations has been proposed to be due to the increase in body mass or, according to another hypothesis, to be also temporally linked to sexual maturation. Furthermore, recently, it has been suggested in rats that the pineal influences not only the pubertal sexual maturation, but even the gonadal and genital development and function of offspring, already during intrauterine life. Investigations are needed to evaluate this hypothesis in humans.

[Intrahepatic cholestasis in pregnancy]. / La colestasi intraepatica in gravidanza.

Intrahepatic cholestasis of pregnancy (ICP) is a syndrome usually manifesting during the third trimester of pregnancy and disappearing after delivery. Multiple factors seem to be involved in pathogenesis of the syndrome; however, ICP appears to take place in women congenitally hypersensitive to estrogens. Typical is pruritus, which may be followed by jaundice and associated with other less common symptoms. The biochemical parameters are characteristically altered: an increase in the levels of aminotransferases (AST, ALT), total bile acids and alkaline phosphatase is observed; while serum GGT are normal. Maternal prognosis is benign. By contrast, a higher risk of acute fetal distress and prematurity has been reported. Various drugs are used in the treatment of ICP. We present the case of a patient treated with S-adenosyl-L-methionine (SaMe). SaMe therapy has proved to be effective in improving the altered biochemical parameters, whose normalization was obtained before delivery.

HIV-1 gp120 glycoprotein induces [Ca2+]i responses not only in type-2 but also type-1 astrocytes and oligodendrocytes of the rat cerebellum.

Cultures of cerebellar cortex cells were exposed to the HIV-1 envelope glycoprotein, gp120, and investigated for cytosolic Ca2+ ion concentration ([Ca2+]i) changes by the fura-2 ratio videoimaging technique while bathed in complete, Na(+)-free or Mg(2+)-free Krebs-Ringer media. At the end of the [Ca2+]i experiments the cells were fixed and immunoidentified through the revelation of markers specific for neurons (microtubule associated protein-2), type-2 (A2B5) or all (glial fibrillary acidic protein) astrocytes, oligodendrocytes (galactocerebroside) or microglia (F4/80 antibody). In complete medium, rapid biphasic (spike-plateau) responses induced by gp120 (0.1-1 nM) were observed in a subpopulation of type-2 astrocytes. In addition, slow but progressive responses were observed in other type-2 cells and oligodendrocytes, whereas type-1 astrocytes showed small responses, if any, and granule neurons did not respond at all. Use of Na(+)-free medium (a condition that blocked another gp120-induced response, cytosolic alkalinization) resulted in an increase in [Ca2+]i response that was appreciable not only in type-2 but also in most type-1 astrocytes, possibly because of the inhibition of the Na+/Ca2+ exchanger and the ensuing decrease in Ca2+ extrusion. Granule neurons, including those in direct contact with responsive astrocytes, remained unresponsive, even when the experiments were carried out in Mg(2+)-free medium supplemented with glycine, a condition that favors activation of the glutamatergic N-methyl-D-aspartate (NMDA) receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of the HIV-1 envelope glycoprotein gp120 in cerebellar cultures. [Ca2+]i increases in a glial cell subpopulation.

The various types of cells present in cultures prepared from the postnatal rat cerebellum, identified by their gross morphology and immunocytochemistry, were loaded with the specific dye fura-2 and analysed individually for [Ca2+]i changes induced by the HIV-1 envelope glycoprotein gp120 and a variety of other treatments. In granule neurons [Ca2+]i increases were induced by high KCl and glutamate (mainly through the NMDA receptor) while in type-1 astrocytes this effect was observed after serotonin, carbachol and also quisqualate. In contrast, administration of gp120 was always without effect in these cells. Type-2 astrocytes (an arborized cell type responsive to agonists targeted to the glutamatergic AMPA and cholinergic receptors) were also most often unresponsive to the viral glycoprotein. However, among the cells exhibiting the arborized phenotype, a subpopulation (approximately 13%) responded to gp120 with conspicuous [Ca2+]i increases sustained by both release from intracellular stores and influx across the plasma membrane. These responses to the viral protein did not involve activation of either voltage-gated Ca2+ channels or glutamatergic receptors. Although not yet conclusively identified by specific cytochemical markers, the gp120-responsive cells resemble type-2 astrocytes and differ from neurons and type-1 astrocytes both in gross phenotype and in a number of receptor/channel properties: positivity to AMPA and cholinergic agonists; negativity to NMDA, serotonin and high KCl. From these results it is concluded that a subpopulation of glial cells is affected by gp120. The role of these cells in HIV brain infection and damage requires further studies to be precisely established.

Regulation of intracellular calcium in cerebellar granule neurons: effects of depolarization and of glutamatergic and cholinergic stimulation.

The regulation of the cytosolic free Ca2+ concentration ([Ca2+]i) was investigated by microfluorimetry in single cerebellar granule neurons exposed to various treatments (high K+, glutamate, or acetylcholine) and drugs. The responses to the treatments developed asynchronously during cell culture, with high K+ and glutamate reaching their maxima at 6 and 7 days in vitro and acetylcholine at 9 days in vitro. The biphasic [Ca2+]i transients induced by high K+ (an initial peak, followed by a plateau 30-40% of the peak, both sustained by dihydropyridine-sensitive voltage-gated Ca2+ channels) were dissipated by washing with fresh medium or, more rapidly, by addition of excess EGTA (t1/2 = 11 +/- 2 and 3 +/- 0.6 s, respectively). Compared to those induced by high K+, the [Ca2+]i transients induced by glutamate administered in Mg2(+)-free medium were much more variable. An initial peak, sustained by voltage-gated Ca2+ channels, was visible in only approximately 50% of the cells and disappeared when multiple glutamate pulses were administered. In the rest of the population, the transients were monophasic, with persistent plateaus sustained only in part (30-40%) by voltage-gated Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Multiple actions of SC 38249: the blocker of both voltage-operated and second messenger-operated Ca2+ channels also inhibits Ca2+ extrusion.

((+-)-1,-2,3-bis-[(4-Methoxyphenyl)-methoxy]propyl)-1H-imidazole (SC 38249) and its 4-methoxyphenetyl analogue (SKF 96365) have been recently reported to block not only voltage-operated Ca2+ channels, but also the channels (second messenger-operated) that open after receptor activation of polyphosphoinositide hydrolysis in smooth muscle fibers and platelets. Fura-2 fluorescence studies in cerebellar neurons, glial and PC12 cells confirmed these effects of SC38249 and in addition demonstrated that the drug causes an inhibition of Ca2+ extrusion, presumably via the Ca2+ ATPase. This effect was particularly evident when [Ca2+]i was increased, regardless of treatment (glutamate or ionomycin). In contrast, the NMDA receptor channel activated by glutamate was not affected by SC 38249.