Luigi Maiolino

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.

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.

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.

Analytical approaches to the diagnosis and treatment of aging and aging-related disease: redox status and proteomics

Abstract Basal levels of oxidants are indispensible for redox signaling to produce adaptive cellular responses such as vitagenes linked to cell survival; however, at higher levels, they are detrimental to cells, contributing to aging and to the pathogenesis of numerous age-related diseases. Aging is a complex systemic process and the major gap in aging research reminds the insufficient knowledge about pathways shifting from normal “healthy” aging to disease-associated pathological aging. The major complication of normal “healthy” aging is in fact the increasing risk of age-related diseases such as cardiovascular diseases, diabetes mellitus, and neurodegenerative pathologies that can adversely affect the quality of life in general, with enhanced incidences of comorbidities and mortality. In this context, global “omics” approaches may help to dissect and fully study the cellular and molecular mechanisms of aging and age-associated processes. The proteome, being more close to the phenotype than the transcriptome and more stable than the metabolome, represents the most promising “omics” field in aging research. In the present study, we exploit recent advances in the redox biology of aging and discuss the potential of proteomics approaches as innovative tools for monitoring at the proteome level the extent of protein oxidative insult and related modifications with the identification of targeted proteins.

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.

Early history of neurofibromatosis type 2 and related forms: earliest descriptions of acoustic neuromas, medical curiosities, misconceptions, landmarks and the pioneers behind the eponyms

As in many diseases, exactly which was the first case report of “neurofibromatosis” and who truly deserves the eponymous for credit have been a matter of debate [6, 42, 66]. Certainly, in the past centuries, several renowned “patients” taken from fiction or reality have been labelled as having this condition and, among all, Joseph Merrick also known as the “elephant man” [11, 41, 77, 87] and Quasimodo the “hunchback” of “Notre Dame de Paris” by Victor Hugo [12, 76] are two infamous examples who played an important role in the distorted popular misconception of the disease. The history of neurofibromatosis (in this case neurofibromatosis type 1—NF1), in fact, can be traced to ancient times, if descriptions of grotesque or distorted persons are considered [1, 6, 37, 42, 51, 54, 100]. Similarly, reports of early examples of neurofibromatosis type 2 (NF2) or schwannomatosis sufferers can be traced in descriptions, illustrations or portraits dated as far back as the eighteenth century [1, 6, 42]. In this article, we will review these developments focusing on the most acknowledged descriptions of patients with NF2 in history.

Cytologic aspects of the nasal respiratory epithelium throughout the menstrual cycle.

A prospective study was performed to investigate the changes in nasal cytology that occur in healthy premenopausal women throughout the menstrual cycle. Eighty-eight women with an ovulatory menstrual cycle underwent nasal sampling with a cytobrush by direct vision of the middle and inferior nasal turbinates during the follicular, periovular, and luteal phases of the menstrual cycle, and the specimens were evaluated with the maturation index. Hematoxylin-eosin staining showed the cytologic aspects of the nasal respiratory epithelium and of vaginal smears according to the three different phases of the menstrual cycle. Along with the vaginal cells, the nasal respiratory epithelium is an ovarian steroid target.

Pediatric autoimmune neuropsychiatric disorder associated with group a streptococcal infection: the role of surgical treatment.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) is a well-defined syndrome in which tics (motor and/or vocal) and/or obsessive compulsive disorders (OCD) consistently exacerbate in temporal correlation to a Group A beta-haemolytic streptococcal infection. In children with PANDAS, there is speculation about whether tonsillectomy or adenotonsillectomy might improve the neuropsychiatric course. Our objective was to examine whether such surgery impacted remission or, in patients without remission, modified clinical course of the disease, streptococcal antibody titers, neuronal antibodies or clinical severity of Obsessive-Compulsive Disorder (OCD) and/or tics. Study participants (n = 120) with positive PANDAS criteria were recruited, examined, and divided into surgical or non-surgery groups. The surgical group consisted of children with tonsillectomy or adenotonsillectomy (n=56). The remaining children were categorized as non-surgery (n=64). Clinical follow-up was made every 2 months for more than 2 years. Surgery did not affect symptomatology progression, streptococcal and neuronal antibodies, or the clinical severity of neuropsychiatric symptoms in these children. In conclusion, in our series clinical progression, antibody production, and neuropsychiatric symptom severity did not differ on the basis of surgical status. We cannot uphold surgical management as likely to impact positive remission rates, course of OCD/tics, or antibody concentrations in children with PANDAS.