Adherence in children with growth hormone deficiency treated with r-hGH and the easypod™ device.

PURPOSE: Poor adherence to recombinant human growth hormone (r-hGH) therapy is associated with reduced growth velocity in children with growth hormone deficiency (GHD). This twelve-month observational study was to assess adherence in r-hGH patients treated with the easypod™, an electronic, fully automated injection device designed to track the time, date and dose administered. METHODS: Ninety-seven prepubertal patients receiving r-hGH therapy were included in the study from ten Italian clinical sites and 88 completed the study. To avoid possible confounding effects, only GHD patients (79/88; 89.7 % of the overall study population) were considered in the final analysis. The primary endpoint-adherence to treatment-was calculated as the proportion of injections correctly administered during the observational period out of the expected total number of injections. The relevant information, tracked by the easypod™, was collected at months 6 (V1) and 12 (V2) after baseline (V0). At study termination, adherence data were partially available from 16 patients and fully available from 53 patients. As secondary endpoints, serum IGF-1 levels, fasting serum glucose and insulin levels and key anthropometric characteristics (height, waist circumference and BMI) were also determined. RESULTS: The easypod™ data showed that 56.7 % of the patients were considered to be fully (≥92 %) adherent to their treatment throughout the period V0-V2. Treatment improved stature, significantly increased IGF-1 and produced a non-significant increase in blood glucose and insulin levels. CONCLUSIONS: The injection-recording system and other characteristics of easypod™ could enhance the ability of physicians to monitor adherence to r-hGH treatment.

Growth hormone treatment of adolescents with growth hormone deficiency (GHD) during the transition period: results of a survey among adult and paediatric endocrinologists from Italy. Endorsed by SIEDP/ISPED, AME, SIE, SIMA.

Treatment of adolescents with growth hormone deficiency (GHD) during the transition period is a controversial issue. This paper is a contribution from the Italian community of paediatric and adult endocrinologists surveyed in a Delphi panel. The Delphi method is a structured communication technique, originally developed as a systematic, interactive forecasting method that relies on a panel of experts. The experts answer questionnaires in two or more rounds. There was substantial agreement on the definition of the problems associated with the diagnosis and treatment of adolescents with GHD in the transition period, as well as on the identification of the controversial issues which need further studies. There is general consensus on the need of re-testing all isolated idiopathic GHD after at least 30-day withdrawn from treatment, while in patients with multiple pituitary deficiency and low IGF-I levels there is generally no need to re-test. In patients with permanent or confirmed GHD, a starting low rhGH dose (0.01-0.03 mg per day) to be adjusted according to IGF-I concentrations is also widely accepted. For those continuing treatment, the optimal therapeutic schedule to obtain full somatic maturation, normalization of body composition and bone density, cardiovascular function and Quality of Life, need to be evaluated.

A large view of CYP21 locus among Sicilians and other populations: identification of a novel CYP21A2 variant in Sicily.

BACKGROUND: Several mutations in CYP21 locus cause 21-hydroxylase deficiency (21-OHD). The most common mutations are widespread among different geographic areas and their frequencies have been also reported to differ among certain populations. AIM: To obtain a large view on the frequencies of the most common mutations in the CYP21 locus, in Sicily, in the Mediterranean and other major geographic areas worldwide. SUBJECTS AND METHODS: Three hundred and eight unrelated CYP21A2 alleles leading 21-OHD in Sicily were genetically typed and compared with other series previously reported in Sicily and in surrounding regions. An analysis of the frequencies of the different geographic areas was also carried out. CYP21A2 typing was carried out using PCR-restriction fragment length polymorphism (RFLP), for the detection of the CYP21A2 deletion, while sequencing analysis was performed to evaluate all the missense/non-sense mutations. RESULTS: Our study revealed that p.V281L (44.4%), I2splice (21.6%) and p.P30L (11.2%) were very frequent alleles, del8bp (0.4%) was found very rarely in Sicily and a novel mutation leading to non-classical phenotype, p.L198F, was also discovered in this population. Allele frequencies were found to be significantly different from previously observed frequencies in Sicily. In addition, here we present the most significant frequency modifications among different geographic areas worldwide. CONCLUSIONS: As the distribution of the disease CYP21A2 alleles is heterogeneous around the world, the knowledge of the relative distributions allows a better management of 21-OHD for fetuses and newborns in different geographic areas.

Magnetic-free Extended Kalman Filter for upper limb kinematic assessment in Yoga.

Human motion analysis is gaining increased importance in several fields, from movement assessment in rehabilitation to recreational applications such as virtual coaching. Among all the technologies involved in motion capture, Magneto-Inertial Measurements Units (MIMUs) is one of the most promising due to their small dimensions and low costs. Nevertheless, their usage is strongly limited by different error sources, among which magnetic disturbances, which are particularly problematic in indoor environments. Inertial Measurement Units (IMUs) could, thus, be considered as alternative solution. Indeed, relying exclusively on accelerometers and gyroscopes, they are insensitive to magnetic disturbances. Even if the literature has started to propose few algorithms that do not take into account magnetometer input, their application is limited to robotics and aviation. The aim of the present work is to introduce a magnetic-free quaternion based Extended Kalman filter for upper limb kinematic assessment in human motion (i.e., yoga). The algorithm was tested on five expert yoga trainers during the execution of the sun salutation sequence. Joint angle estimations were compared with the ones obtained from an optoelectronic reference system by evaluating the Mean Absolute Errors (MAEs) and Pearson's correlation coefficients. The achieved worst-case was 6.17°, while the best one was 2.65° for MAEs mean values. The accuracy of the algorithm was further confirmed by the high values of the Pearson's correlation coefficients (lowest mean value of 0.86).Clinical Relevance- The proposed work validated a magnetic free algorithm for kinematic reconstruction with inertial units. It could be used as a wearable solution to track human movements in indoor environments being insensitive to magnetic disturbances, and thus could be potentially used also for rehabilitation purposes.

Carotid Intraplaque-Hemorrhage Volume and Its Association with Cerebrovascular Events.

BACKGROUND AND PURPOSE: Our aim was to assess the relationship between volume and percentage of intraplaque hemorrhage measured using CT and the occurrence of cerebrovascular events at the time of CT. MATERIALS AND METHODS: One-hundred-twenty-three consecutive subjects (246 carotid arteries) with a mean age of 69 years who underwent CTA were included in this retrospective study. Plaque volume of components and subcomponents (including intraplaque hemorrhage volume) was quantified with dedicated software. RESULTS: Forty-six arteries were excluded because no plaque was identified. In the remaining 200 carotid arteries, a statistically significant difference was found between presentation with cerebrovascular events and lipid volume (P = .002), intraplaque hemorrhage volume (P = .002), percentage of lipid (P = .002), percentage of calcium (P = .001), percentage of intraplaque hemorrhage (P = .001), percentage of lipid-intraplaque hemorrhage (P = .001), and intraplaque hemorrhage/lipid ratio (P = .001). The highest receiver operating characteristic area under the curve was obtained with the intraplaque hemorrhage volume with a value of 0.793 (P = .001), percentage of intraplaque hemorrhage with an area under the curve of 0.812 (P = .001), and the intraplaque hemorrhage/lipid ratio with an area under the curve value of 0.811 (P = .001). CONCLUSIONS: Results of our study suggest that Hounsfield unit values <25 have a statistically significant association with the presence of cerebrovascular events and that the ratio intraplaque hemorrhage/lipid volume represents a strong parameter for the association of cerebrovascular events.

Unusual EEG pattern linked to chromosome 3p in a family with idiopathic generalized epilepsy.

OBJECTIVE: To map the gene causing an unusual EEG pattern of delta bursts that appears to segregate as an autosomal dominant trait in an Italian family. The EEG pattern was observed in four family members affected by idiopathic generalized epilepsy (IGE) and in six other clinically unaffected members. METHODS: All available family members underwent clinical and EEG examination. DNA samples were obtained and used to perform a whole-genome scan with 270 microsatellite markers. After the first linked marker was identified, 12 additional markers in the same chromosomal region were tested to confirm linkage and define a candidate interval. RESULTS: The gene responsible for the EEG trait was mapped to an 11-cM interval on the proximal short arm of chromosome 3 (3p14.2-p12.1). CONCLUSION: In this family, a characteristic EEG activity is due to the effect of a single gene on chromosome 3p. A gene encoding a Ca2+ channel subunit maps in the interval and is a potential candidate for the trait. The clinical expression of epilepsy in four family members may reflect the interaction of additional genes, though environmental or other factors cannot be excluded.

Phenserine: a physostigmine derivative that is a long-acting inhibitor of cholinesterase and demonstrates a wide dose range for attenuating a scopolamine-induced learning impairment of rats in a 14-unit T-maze.

Phenserine ((-)-N-phenylcarbamoyl eseroline), a carbamate analog of physostigmine (Phy), is a long-acting inhibitor of cholinesterase. We have assessed the potential clinical value of phenserine for cholinomimetic therapy of cognitive impairments associated with aging and Alzheimer's disease by evaluating its duration of in vivo activity against rat plasma acetylcholinesterase (AChE) and its effect on attenuating a scopolamine-induced impairment in learning performance of young rats in a shock-motivated 14-unit T-maze. Phenserine achieved maximum AChE inhibition of 73.5% at 5 min and maintained a high and relatively constant inhibition for more than 8 h. For analysis of effects on learning performance, 69, 3-month-old male Fischer-344 rats were pretrained in a straight runway to avoid electric footshock. On the following day, each animal received 15 trials in the 14-unit T-maze. Sixty minutes prior to the maze training, each rat received the first IP injection of either vehicle (Tween 80, ethanol and 0.9% NaCl) or phenserine at 1.5, 3.0, 4.0, 5.0, 7.5, or 10.0 mg/kg. Then 30 min prior to the training, each animal received a second IP injection of either 0.9% NaCl or scopolamine hydrochloride (0.75 mg/kg; SCOP). Compared to the vehicle-SCOP group, all but the 7.5 mg/kg dose of phenserine significantly ameliorated error performance, runtime, shock frequency and shock duration in SCOP-treated rats at the final block of three trials. Appearing to have a long effect and a wide therapeutic window, phenserine deserves further study as a cognitive enhancer.

8-OH-DPAT impairs spatial but not visual learning in a water maze by stimulating 5-HT1A receptors in the hippocampus.

The effect of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, on spatial and non-spatial learning in a water maze was studied using two tasks of equal difficulty, with the same motor, motivational and reinforcement demands. Rats were examined for choice accuracy in a two-platform spatial discrimination task. Rats treated subcutaneously with 100 micrograms/kg 8-OH-DPAT were impaired in choice accuracy with no effect on latency. Treated rats made more errors of omission than controls only on days 1 and 2 of training. Infusion of 1 microgram/microliter spiroxatrine (SPX) or 5 micrograms/microliters of (+)WAY100135, two potent 5-HT1A receptor antagonists, in the CA1 region of the dorsal hippocampus antagonized the impairment in choice accuracy caused by 8-OH-DPAT. The effect on errors of omission on days 1 and 2 of training were not significantly modified by spiroxatrine or (+)WAY100135. Rats treated with 8-OH-DPAT were not impaired in their ability to learn a visual discrimination in a water maze. The results suggest that stimulation of 5-HT1A receptors in the CA1 region of the dorsal hippocampus impairs spatial but not visual discrimination in rats.

Reduced density of NMDA receptors and increased sensitivity to dizocilpine-induced learning impairment in aged rats.

About 20 min prior to training in a shock-motivated 14-unit T-maze, young (3-4 months) and aged (24-25 months) male Fischer-344 rats were given s.c. injections of either saline or dizocilpine (MK-801, 0.02 or 0.04 mg/kg), a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. The aged rats showed a dose-dependent impairment in maze performance. Deficiencies were manifested as increases in errors, in runtime from start to goal, and in the number and duration of shocks received. In contrast, young rats exhibited no detrimental effects of dizocilpine on maze performance. Analysis of [3H]glutamate binding in these rats revealed a marked age-related decline in NMDA receptor binding in hippocampus. A significant correlation was observed between errors in the maze and hippocampal [3H]-glutamate binding, but the correlation was positive, i.e., rats that made the most errors had the highest level of NMDA receptor binding. Thus, compared to young rats, aged rats were more sensitive to the behavioral effects of NMDA receptor antagonism and they showed a hippocampal loss of [3H]glutamate in binding, which may be related to the increased sensitivity to dizocilpine. The positive correlation between poor maze performance and NMDA receptor binding suggests that the behaviors assessed involve complex interactions between NMDA receptors and other neuronal systems in the hippocampus.

Peripheral effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its main metabolite 1-methyl-4-phenylpyridinium ion (MPP+) in the rat.

The effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its main metabolite 1-methyl-4-phenyl-pyridinium ion (MPP+) on catecholamine concentrations was tested in some peripheral organs of the rat. Acute injection of either compound caused a marked depletion of heart noradrenaline (NA). MPP+ had more effect than the parent compound. MPTP had no effect on adrenal catecholamines while its metabolite was effective, but only after several hours. Repeated MPTP and MPP+ injections (20 mg/kg X 5) resulted in marked depletion of heart NA and adrenal gland adrenaline. Clear recovery was observed in both organs 10 days after treatment.

The long-acting cholinesterase inhibitor heptyl-physostigmine attenuates the scopolamine-induced learning impairment of rats in a 14-unit T-maze.

Heptyl-physostigmine (heptyl-Phy), a new carbamate derivative of physostigmine (Phy), has been assessed for potential clinical value by evaluating its in vitro activity against human erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE), its duration of in vivo activity against rat plasma AChE, and its effects on attenuating a scopolamine-induced impairment in learning performance of young rats in a 14-unit T-maze. Heptyl-Phy demonstrated potent cholinesterase inhibition, with activity similar to that of Phy against AChE, IC50 values 21.7 +/- 2.0 nM and 27.9 +/- 2.4 nM, respectively, and significantly greater than that of Phy against BChE, IC50 values 5.0 +/- 0.1 nM and 16.0 +/- 2.9 nM, respectively. Heptyl-Phy achieved maximum AChE inhibition of 92.5% at 60 min and maintained a high and relatively constant inhibition for more than 8 h. For analysis of effects on learning performance, heptyl-Phy at 1.0, 1.5, 2.0 or 3.0 mg/kg, or vehicle was administered i.p. to 52 3-month-old male Fischer-344 rats 60 min prior to maze training. Thirty minutes prior to training, each animal received either 0.9% NaCl or scopolamine hydrochloride (0.75 mg/kg). Only a 2.0 mg/kg dose of heptyl-Phy significantly reduced the number of errors in scopolamine-treated rats. The other doses did not improve any aspect of maze performance. Although the therapeutic window of heptyl-Phy did not appear wide enough for clinical use, the longer duration of action of heptyl-Phy would appear beneficial.

Activation of partial seizures with motor signs during cyclic alternating pattern in human sleep.

Both interictal and ictal EEG phenomena are commonly activated by functional instability. The different non-REM sleep stages comprise long-lasting periods of cyclic alternating pattern (CAP) in which arousal fluctuates between 'A phases' of greater arousal and 'B phases' of less arousal, and periods in which vigilance maintains a tonic stability (non-CAP). Previous studies have revealed that phase A induces a marked enhancement of generalized EEG paroxysms, a minor though significant activation of focal lesional bursts, but no effect on rolandic functional spikes. Conversely, phase B exerts an inhibitory modulation, especially on bilateral interictal phenomena. Because of the opposite influence of phase A and phase B also on muscle tone, we assessed the amount and distribution of nocturnal partial motor seizures in 6 subjects affected by focal epilepsy. The polysomnograms included 45 motor seizures, 43 of which occurred during non-REM sleep. Nocturnal fits were significantly more frequent in stages 1 and 3 (P less than 0.0001). Among the non-REM seizures, 42 appeared in CAP (P less than 0.0001) and always in phase A. The transient arousal and the concomitant muscle tone activation expressed by phase A of CAP is likely to support the motor components of nocturnal seizures. Sleep analysis in terms of CAP and non-CAP provides a better understanding of the continuum from subclinical EEG paroxysms to clinical manifestations and of the relations between vigilance and seizure disorders.

Complex maze performance in young and aged rats: response to glucose treatment and relationship to blood insulin and glucose.

In aged rats and humans, impaired glucose regulation has been correlated with poor memory performance, and glucose treatment can result in improved performance. We tested this glucose hypothesis with rats in a 14-unit T-maze that has provided robust evidence of age-related performance decline. Aged (24-25 month) and young (6-7 month) male F-344 rats were pretrained for one-way active avoidance before receiving complex maze training (4 daily trials over 5 days) with the contingency of moving through each of 5 segments to avoid footshock. Ten min before daily training, aged rats received either saline or glucose in doses of 10, 100, or 500 mg/kg IP, while young rats received saline. Significant (ps less than 0.05) age-related increases in errors, runtime, and shock duration were observed. Glucose treatment had no significant effect on the number of maze errors committed; however, performance variables such as runtime and shock duration appeared to be reduced in rats receiving glucose. About 4-6 weeks later, a sample of these rats was fasted overnight, injected IP with glucose (150 mg/kg), and bled at various postinjection intervals to obtain estimates of blood glucose and insulin levels. Significant correlations (ps less than 0.05) were observed between maze errors and baseline glucose levels, r(21) = -.62, and peak glucose response, r(19) = .49. However; within the aged group, significant correlations (ps less than 0.01) with maze errors emerged only for baseline glucose, r(13) = -.69, and peak insulin response, r(13) = -.65. Thus, regulation of insulin, but not glucose, appeared related to learning abilities among aged rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombosis of parietal, but not striate, cortex impairs acquisition of a 14-unit T-maze in the rat.

We evaluated parietal cortex (PCTX) involvement in learning a shock-motivated, 14-unit T-maize in young F344 rats. In Experiment 1, each rat was placed into a stereotaxic instrument, and the scalp was retracted before either the photosensitive dye, rose bengal, or saline (CON) was provided via a jugular catheter. After 60 s, halogen lamps were used to illuminate the cranium bilaterally over PCTX for 40 min to activate the dye and generate a thrombus in dye-injected rats. Active avoidance pretraining in a straight runway occurred 12 days after surgery. Each rat was provided acquisition (ACQ) trials in the 14-unit T-maze 24-h later. The PCTX rats were impaired relative to CON in errors, run time, alternation errors, and shock frequency measures in the 14-unit T-maze, but not in shock duration. The thrombosis extended to areas comprising anteromedial and posterior PCTX, and also into the striate cortex (SCTX). In Experiment 2, rats were divided into four groups: a PCTX group that received bilateral illumination; PCTX+SCTX and SCTX groups that were illuminated at midline; and a CON group that received the surgery and either dye or illumination. Only PCTX differed from CON, with maze performance similar to Experiment 1. The thrombosis for the PCTX group in Experiment 2 was confined to anteromedial and posterior PCTX. Thus, PCTX, but not SCTX, was implicated in ACQ of this maze task, suggesting that PCTX might be involved in the robust age-related impairments in ACQ previously observed.

NMDA receptor channel antagonism by dizocilpine (MK-801) impairs performance of rats in aversively motivated complex maze tasks.

To determine the involvement of the N-methyl-D-aspartate (NMDA) receptor in shock-motivated complex maze performance, the drug dizocilpine (DIZO; a.k.a. MK-801) was administered a) to naive, 3-month-old male F-344 rats prior to acquisition (AQ) in the 14-unit T-maze (Experiment 1), and b) to well-trained 11-month-old male F-344 rats prior to testing in a delayed-matching-to-sample (DMTS) task in the detour maze (Experiment 2). For Experiment 1, rats first were pretrained in a straight runway on one-way active avoidance (13/15 correct avoidances) for a maximum of 30 trials. On the following day, either DIZO 0.025 (n = 8), 0.05 (n = 8), 0.1 (n = 8), mg/kg, or saline (SAL; n = 15) was administered subcutaneously (SC) 20 min prior to 15 AQ trials in the shock-motivated 14-unit T-maze. The highest dose disrupted all measures of maze performance including errors, alternation errors, runtime, shock duration and frequency, but also produced marked motor ataxia. The 0.05-mg/kg group displayed significant impairment in AQ of this task but only on the cognitive measures, errors and alternation errors, and the 0.025-mg/kg group was impaired on the alternation measure only. One week later, the 15 SAL rats were divided into 2 groups and tested on retention with either SAL or 0.05 mg/kg DIZO. No effects on maze performance were observed. For Experiment 2, after receiving extensive pretraining in the shock-motivated detour maze, 7 rats were exposed to a novel sequence of 4 problems (P) during each of 7 daily sessions. Performance was evaluated 20 min after SC injection of either DIZO--0.025, 0.05, 0.125 mg/kg, or SAL. The 0.125-mg/kg dose caused extreme motor ataxia which precluded testing during that session. The 0.05-mg/kg but not the 0.025-mg/kg dose significantly disrupted performance on both error and trials to criterion measures. Both problem and interaction effects were significant. Disruption was most evident on two specific problems, those involving a side change from the first to second detour. Also, rats had more difficulty switching sides from problem to problem (few errors on P-1 and most on P-4), suggesting proactive interference effects. In sum, DIZO was observed to significantly disrupt performance in both mazes in a dose-related manner similar to effects observed in previous studies following administration of the anticholinergic drug scopolamine. For the 14-unit T-maze, the present results simulate age-related deficits previously found in acquisition of that task.

CR 2249: a new putative memory enhancer. Behavioural studies on learning and memory in rats and mice.

The effects of S-4-amino-5-[4,4-dimethylcyclohexyl)amino]-5-oxopentanoic acid (CR 2249), a new entity selected from a new series of glutamic acid derivatives, has been investigated in different paradigms for screening nootropics. CR 2249 ameliorated the memory retention deficit produced by scopolamine in step-through-type passive avoidance in rats and by electroconvulsive shock in step-down-type passive avoidance in mice. CR 2249 was also capable of improving performance in behavioural tests of learning and memory in the absence of cholinergic hypofunction or cognitive deficit. The activity was determined using different passive and active avoidance behavioural test procedures on rats. CR 2249 was active only when given 45 min before training and did not show any effect when administered immediately after the learning training or before the retention trial. No changes in the general behaviour or motor activity of the animals were observed, indicating that CR 2249 effects cannot be attributed to sensory-motor deficit. Microdialysis experiments have shown that CR 2249 significantly increased noradrenaline release in the hippocampus of freely moving rats and reduced 3,4-dihydroxyphenylglycol efflux. These effects have led us to hypothesize that CR 2249 memory effect might be mediated by a direct or indirect action on noradrenergic transmission. These behavioural results suggest that this new agent has clinical application in memory disorders.

Direct autofluorescence during CO2 laser surgery of the larynx: can it really help the surgeon?

Herein we assessed the impact of direct autofluorescence during intraoperative work-up on obtaining superficial free resection margins, identifying new areas of malignant transformation and altering disease-free survival and local control at 3 years in patients submitted to transoral laser surgery (TLS) for early glottic cancer. Prospective cohort evaluation was carried out on the diagnostic accuracy of the superficial extent and TNM staging in 73 patients with glottic carcinoma undergoing transoral CO2 laser surgery. The use of direct autofluorescence was associated with superficial disease-free margins in 97.2% of cases, and with superficial close margins in 2.8%. The improvement in diagnostic accuracy was 16.4%; in 8.2% of cases, there was upstaging of the TNM classification (in one case, a second neoplastic area in a different laryngeal site was observed and considered to be a second endolaryngeal primary). The sensitivity of direct autofluorescence was 96.5% with a specificity of 98.5%. Overall, 3-year disease-specific survival and local control with laser alone were, respectively: T1a (97.5%, 100%), T1b (86.7%, 86.7%), T2 (88.9%, 88.9%). This study demonstrates that direct autofluorescence can help to identify positive superficial margins, and has a favourable impact on disease-specific survival and local control at 3 years.

How the operated larynx ages.

After open partial laryngectomy (HOPL), many patients experience deterioration of laryngeal function over time. The aim of this study was to evaluate laryngeal functional outcome at least 10 years after surgery in a cohort of 80 elderly patients. The incidence of aspiration pneumonia (AP) and objective/subjective laryngeal functional assessments were carried out. Eight patients experienced AP including four with repeated episodes. A significant association was observed between AP and severity of dysphagia (p < 0.001). Dysphagia was more pronounced than in a normal population of similar age, but less than would be expected. There was a significant association between the type of intervention and grade of dysphagia/dysphonia; a difference in voice handicap was found, depending on the extent of glottic resection. After HOPL, laryngeal function was impaired, but this did not significantly affect the quality of life. AP is more frequent in the initial post-operative period, and decreases in subsequent years.