Agostino Serra

Auditory brainstem response in postmenopausal women treated with hormone replacement therapy: a pilot study.

Objective: To research the nongenital audiological target for gonadal steroids in postmenopausal women who are treated with hormone replacement therapy. Design: Fifty postmenopausal volunteers were treated with hormone replacement therapy. Women with an intact uterus had sequential weekly transdermal estradiol plus nomegestrole acetate 5 mg orally for 12 days per month or a continuous daily oral dose of conjugated estrogen 0.625 mg and medroxyprogesterone acetate 5 mg tablet. Eighteen surgically postmenopausal women received a weekly transdermal estradiol system. Twenty‐five postmenopausal volunteers—5 with a natural menopause and 10 with a surgical menopause—and 20 premenopausal normally cycling women were used as a control group. Each woman performed auditory brainstem response by auditory‐evoked potentials for waves I, III, and V and for interpeak I‐III, I‐V, and III‐V intervals. Results: Women who were treated with hormone replacement therapy showed wave latencies and interpeak latencies shorter than those for postmenopausal women in the control group (p ≤ 0.05), overlapping those of the premenopausal women (p > 0.05). Women who were treated with estrogen replacement therapy showed shorter time latencies than those treated with combined hormone replacement therapy (p ≤ 0.05). Conclusions: Our data suggest that fluctuating hormone levels cause changes in auditory brainstem response waves, even if the exact mechanism of activity of the gonadal steroids is not clear. However, we believe that estrogen may influence the neuronal plasticity, the metabolic levels of neurotransmitters, and thus the neuronal conduction time into the audiological system. (Menopause 2000;7:178‐183.

Heat shock proteins and hormesis in the diagnosis and treatment of neurodegenerative diseases

Modulation of endogenous cellular defense mechanisms via the vitagene system represents an innovative approach to therapeutic intervention in diseases causing chronic tissue damage, such as in neurodegeneration. The possibility of high-throughoutput screening using proteomic techniques, particularly redox proteomics, provide more comprehensive overview of the interaction of proteins, as well as the interplay among processes involved in neuroprotection. Here by introducing the hormetic dose response concept, the mechanistic foundations and applications to the field of neuroprotection, we discuss the emerging role of heat shock protein as prominent member of vitagene network in neuroprotection and redox proteomics as a tool for investigating redox modulation of stress responsive vitagenes. Hormetic mechanisms are reviewed as possibility of targeted therapeutic manipulation in a cell-, tissue- and/or pathway-specific manner at appropriate points in the neurodegenerative disease process.

Mucosal Leishmaniasis: An Underestimated Presentation of a Neglected Disease

We present a review of current knowledge about mucosal leishmaniasis (ML). Although involvement of mucous membranes is classically admitted in New World leishmaniasis, particularly occurring in infection by Leishmania (L.) braziliensis species complex, ML is also a possible presentation of Old World leishmaniasis, in either L. donovani or L. major species complex infections. Thus, ML has to be considered not only as a Latin American disease but as an Old and New World disease. We describe ML epidemiology, pathogenesis, clinics, diagnosis, and therapy. Considering both its highly disfiguring lesions and its possible lethal outcome, ML should not be underestimated by physicians. Moreover, leishmaniasis is expected to increase its burden in many countries as sandfly vector distribution is widespreading towards non-endemic areas. Finally, the lack of clear understanding of ML pathogenesis and the absence of effective human vaccines strongly claim for more research.

Effects of patch or gel estrogen therapies on auditory brainstem response in surgically postmenopausal women: a prospective, randomized study

OBJECTIVE To study the effects of gonadal steroids on the nongenital audiological target in surgically postmenopausal women treated with patch or gel transdermal estrogen therapy (ET). DESIGN Prospective randomized study. SETTING Research Group for Sexology, University of Catania, Italy. PATIENT(S) One hundred twenty-two surgically postmenopausal women. INTERVENTION(S) Transdermal E(2) by patch or gel, and evaluation of auditory brainstem response by auditory-evoked potentials for waves I, III, and V latencies, and for interpeak I-III, I-V, and III-V intervals. MAIN OUTCOME MEASURE(S) Changes in auditory wave latencies and in interpeak intervals during treatment with ET with respect to baseline levels. RESULT(S) One hundred two women completed the study. Forty-eight subjects used E(2) patches and 54 E(2) gel. No significant difference was observed in plasma E(2) improvement and in auditory brainstem response values with the two estrogen (E) formulations. The wave latencies and the interpeak intervals showed lower values during the E treatment than at baseline. CONCLUSION(S) Auditory brainstem response seems to depend on the type of E given. Our data suggest that fluctuating E levels act on waves, even if the exact mechanism of the gonadal steroids is not clear. However, we believe that E could influence neuronal plasticity, the metabolic levels of neurotransmitters, and thus, the neuronal conduction time into the audiological system.

Auditory brain stem response throughout the menstrual cycle.

A prospective study was performed to evaluate the changes in the auditory brain stem response (ABR) that occur in healthy premenopausal women throughout the menstrual cycle. Ninety-four women with ovulatory menstrual cycles underwent ABR testing by auditory evoked potentials for wave I, III, and V latencies and for interpeak I-III, I-V, and III-V intervals during the follicular, periovular, and luteal phases of the menstrual cycle. The wave latencies and the interpeak intervals showed shorter values during the periovular phase than during the luteal phase (p < .05) and shorter values during the follicular phase for wave I (p < .05) and interpeak interval I-V (p < .05). The ABR seems to be influenced by the variations of ovarian steroids that occur during the menstrual cycle.

Management of acute pharyngitis in children: summary of the Italian National Institute of Health guidelines.

BACKGROUND Discrepancies in the management of pharyngitis in children have been reported in Europe and the United States, and recommendations concerning the use of clinical scores, rapid antigen diagnostic tests (RADTs) or throat cultures, and the indications for antibiotic treatment largely differ. OBJECTIVE This article summarizes the Italian guidelines on the management of pharyngitis in children issued by the National Institute of Health. METHODS A multidisciplinary panel of experts (the Guidelines Development Group) developed and used a set of key questions to conduct a systematic review of the literature. Relevant publications in English were identified through a systematic review of MEDLINE and the Cochrane Database of Systematic Reviews from their inception through April 30, 2011. Final recommendations were scaled according to the Italian National Guidelines Program grading. RESULTS Eighteen clinical questions were defined, and 44 recommendations were issued. None of the available scoring systems is sufficiently accurate to identify group A β-hemolytic streptococci (GABHS) pharyngitis in settings with low prevalence for rheumatic disease. RADT should be performed by trained personnel in every child with a history and signs/symptoms suggestive of GABHS pharyngitis. RADT is not recommended in children with a McIsaac score of 0 or 1 with ≥2 signs/symptoms suggestive of viral infection. Backup culture in children with negative RADT result is not recommended. Culture test with antibiotic susceptibility assay should be performed exclusively for epidemiologic purposes. Streptococcal antibody titers are of no value in diagnosing acute pharyngitis. Antibiotic therapy is recommended in microbiologically documented GABHS pharyngitis. Because penicillin V is not available in Italy, amoxicillin (50 mg/kg/d in 2-3 doses orally) for 10 days is the first choice of treatment. In noncompliant cases, benzathine penicillin may be administered. Although not routinely recommended due to the high cost and wide spectrum of activity, a 5-day course with a second-generation cephalosporin may be used in noncompliant cases. Macrolides should be limited to children with demonstrated type I hypersensitivity to penicillin. Ibuprofen or paracetamol is recommended for relief of pain or fever associated with discomfort. Because the carrier state is not associated with increased risk of suppurative complications and risk of GABHS transmission to contacts is minimal, the carrier state should never be investigated and treated. Recommendations for the management of suppurative complications are given. CONCLUSIONS This guideline provides a comprehensive, evidence based, tool for the diagnosis and therapy of acute pharyngitis in children.

Bacteriological findings and antimicrobial resistance in odontogenic and non-odontogenic chronic maxillary sinusitis.

The main objectives of this study were to estimate the frequency of chronic maxillary sinusitis of dental origin, and to evaluate the microbiology of odontogenic and non-odontogenic chronic maxillary sinusitis. Aspirates from 59 patients with chronic maxillary sinusitis (47 non-odontogenic, 12 odontogenic), collected during a 3-year period, were microbiologically processed for aerobic and anaerobic bacteria. Moreover, antimicrobial susceptibility was evaluated in the isolated bacteria. In this study, 20 % of chronic maxillary sinusitis cases were associated with a dental origin, and sinus lift procedures were the main aetiological factor. Our microbiological findings showed that all specimens from chronic maxillary sinusitis were polymicrobial. Sixty aerobes and 75 anaerobes were recovered from the 47 cases of non-odontogenic sinusitis (2.9 bacteria per specimen); 15 aerobes and 25 anaerobes were isolated from the 12 patients with odontogenic sinusitis (3.3 bacteria per specimen). The predominant aerobes were Staphylococcus aureus (27) and Streptococcus pneumoniae (16), while the more frequent anaerobes were Peptostreptococcus species (31) and Prevotella species (30). Haemophilus influenzae and Moraxella catarrhalis were absent in sinusitis associated with a dental origin. Overall, 22 % of Staphylococcus aureus isolates were oxacillin-resistant, and 75 % of Streptococcus pneumoniae isolates were penicillin-resistant and/or erythromycin-resistant; 21 % of anaerobic Gram-positive bacteria were penicillin-resistant, and 44 % of anaerobic Gram-negative bacteria were β-lactamase-positive. Vancomycin and quinopristin-dalfopristin had the highest in vitro activity against Staphylococcus aureus and Streptococcus species, respectively; amoxicillin-clavulanate and cefotaxime showed the highest in vitro activity against aerobic Gram-negative bacteria; and moxifloxacin, metronidazole and clindamycin were the most active against anaerobic bacteria.

Double-blind, randomized, multicenter study comparing the effect of betahistine and flunarizine on the dizziness handicap in patients with recurrent vestibular vertigo.

Objective --The aim of this double-blind, randomized, multicenter study was to compare the efficacy of betahistine dihydrochloride (BH) and flunarizine (FL) using the Dizziness Handicap Inventory (DHI), a validated self-assessment questionnaire that has not previously been used in a clinical trial to evaluate antivertigo drugs. Material and Methods --Patients with recurrent vertigo of peripheral vestibular origin and who were severely handicapped by vertigo were randomized to an 8-week course of treatment with oral BH 48 mg daily or oral FL 10 mg daily. The efficacy endpoints were the total DHI score and the physical, functional and emotional subscores. Results --Fifty-two patients completed the study. After 8 weeks of treatment the mean total DHI score and the physical subscore were significantly lower in the BH group compared to the FL group (7.5 and 3.6 points, respectively). The mean total DHI score as well as the three subscores decreased significantly after 4 and 8 weeks in both treatment groups. Conclusion --This study showed that at 8 weeks BH is significantly more effective than FL in terms of improving the total DHI score and the physical subscore. It was also established that the DHI is a useful and reliable method for evaluating the efficacy of antivertigo drugs.

Cytologic aspects of the nasal respiratory epithelium in postmenopausal women treated with hormone therapy

OBJECTIVE To investigate the effects of hormone therapy (HT) on nasal respiratory epithelium in postmenopausal women. DESIGN Prospective open clinical trial. SETTING Outpatient menopausal clinic. PATIENT(S) One hundred three healthy postmenopausal women, of whom 55 treated with HT, and 48 untreated women (controls). INTERVENTION(S) Different regimens of HT by patch, gel, or oral administration. MAIN OUTCOME MEASURE(S) Cytologic changes of nasal, middle and inferior turbinate cells compared with vaginal cytologic findings by using the maturation index. RESULT(S) Hematoxylin-eosin staining for the maturation index confirmed similar trophic cytologic aspects between the nasal respiratory epithelium and vaginal smears in HT-treated women and controls. Women treated with sequential HT or estrogen therapy (ET) showed better trophic characteristics in the nasal cytological samples compared with women treated with continuous combined HT. CONCLUSION(S) Along with vaginal cells the nasal respiratory epithelium is an estrogen target. The activity of HT in the nasal respiratory epithelium may depend on the type of hormone regimen used.

Childhood neurofibromatosis type 2 (NF2) and related disorders: from bench to bedside and biologically targeted therapies

SUMMARY Neurofibromatosis type 2 [NF2; MIM # 101000] is an autosomal dominant disorder characterised by the occurrence of vestibular schwannomas (VSs), schwannomas of other cranial, spinal and cutaneous nerves, cranial and spinal meningiomas and/or other central nervous system (CNS) tumours (e.g., ependymomas, astrocytomas). Additional features include early onset cataracts, optic nerve sheath meningiomas, retinal hamartomas, dermal schwannomas (i.e., NF2-plaques), and (few) café-au-lait spots. Clinically, NF2 children fall into two main groups: (1) congenital NF2 - with bilateral VSs detected as early as the first days to months of life, which can be stable/asymptomatic for one-two decades and suddenly progress; and (2) severe pre-pubertal (Wishart type) NF2- with multiple (and rapidly progressive) CNS tumours other-than-VS, which usually present first, years before VSs [vs. the classical adult (Gardner type) NF2, with bilateral VSs presenting in young adulthood, sometimes as the only disease feature]. Some individuals can develop unilateral VS associated with ipsilateral meningiomas or multiple schwannomas localised to one part of the peripheral nervous system [i.e., mosaic NF2] or multiple non-VS, non-intradermal cranial, spinal and peripheral schwannomas (histologically proven) [schwannomatosis]. NF2 is caused by mutations in the NF2 gene at chromosome 22q12.1, which encodes for a protein called merlin or schwannomin, most similar to the exrin-readixin-moesin (ERM) proteins; mosaicNF2 is due to mosaic phenomena for the NF2 gene, whilst schwannomatosis is caused by coupled germ-line and mosaic mutations either in the SMARCB1 gene [SWNTS1; MIM # 162091] or the LZTR1 gene [SWNTS2; MIM # 615670] both falling within the 22q region and the NF2 gene. Data driven from in vitro and animal studies on the merlin pathway [e.g., post-translational and upstream/downstream regulation] allowed biologically targeted treatment strategies [e.g., Lapatinib, Erlotinib, Bevacizumab] aimed to multiple tumour shrinkage and/or regression and tumour arrest of progression with functional improvement.