Persistent postural-perceptual dizziness: A functional neuro-otologic disorder.

Persistent postural-perceptual dizziness (PPPD) is a functional neuro-otologic disorder that is the most frequent cause of chronic vestibular syndrome. The core vestibular symptoms include dizziness, unsteadiness, and non-spinning vertigo, which are exacerbated by an upright posture or walking, active or passive motion, and exposure to moving or complex visual stimuli. PPPD is mostly precipitated by acute or episodic vestibular diseases; however, its symptoms cannot be accounted for by its precipitants. PPPD is not a diagnosis of exclusion, but may coexist with other structural diseases. Thus, when diagnosing PPPD, the patient's symptoms must be explained by PPPD alone or by PPPD in combination with a structural illness. PPPD is most frequently observed at approximately 50 years of age, with a female predominance. Conventional vestibular tests do not reveal any specific signs of PPPD. However, the head roll-tilt subjective visual vertical test and gaze stability test after exposure to moving visual stimuli may detect the characteristic features of PPPD, that is, somatosensory- and visually-dependent spatial orientation, respectively. Therefore, these tests could be used as diagnostic tools for PPPD. Regarding the pathophysiology of PPPD, neuroimaging studies suggest shifts in interactions among visuo-vestibular, sensorimotor, and emotional networks, where visual inputs dominate over vestibular inputs. Postural control also shifts, leading to the stiffening of the lower body. To treat PPPD, selective serotonin reuptake inhibitors/serotonin noradrenaline reuptake inhibitors, vestibular rehabilitation, and cognitive behavioral therapy are used alone or in combination.

Otic Capsule Demineralization and Hearing Outcome of Stapes Surgery for Osteogenesis Imperfecta in Comparison With Otosclerosis.

OBJECTIVE: To assess the location/number of otic capsule demineralization and hearing outcomes of stapes surgery (SS) for osteogenesis imperfecta (OI) compared with otosclerosis (OS). PATIENTS: This study included 11 and 181 consecutive ears from 6 and 152 patients with OI and OS, respectively. INTERVENTIONS: Demineralization loci observed as hypodense area of the otic capsule were examined using high-resolution computed tomography. All patients underwent SS. MAIN OUTCOME MEASURES: Locations of the hypodense areas were classified into the anterior oval window, anterior internal auditory canal, and pericochlear area. The location/number of hypodense areas and preoperative/postoperative hearing parameters were correlated. Postoperative hearing outcome was evaluated 12 months after surgery. RESULTS: Hypodense area was more frequently observed in OI (9 of 11 ears [81.8%]) than in OS (96 of 181 ears [53.0%]), with significant differences. Multiple sites were involved in 81.8% OI and 18.8% OS patients, showing significant differences. Preoperative air conduction (AC), bone conduction, and air-bone gap (ABG) were 48.9 ± 17.8, 28.0 ± 11.3, and 20.7 ± 8.4 dB, respectively, in OI and 56.2 ± 13.5, 30.5 ± 9.9, and 26.4 ± 9.7 dB, respectively, in OS, demonstrating greater AC and ABG in OS than in OI. Postoperative AC (31.3 ± 20.5 dB), ABG (10.6 ± 10.0 dB), and closure of ABG (12.1 ± 4.7 dB), that is, preoperative ABG minus postoperative ABG of OI, were comparable to those of OS (AC, 30.9 ± 13.3 dB; ABG, 7.0 ± 7.4 dB; closure of ABG, 20.1 ± 11.6 dB). CONCLUSION: OI ears showed more severe demineralization of otic capsule than OS ears. However, favorable hearing outcomes could be obtained through SS for OI and OS ears.

Role of Common Antihypertensives in the Growth of Abdominal Aortic Aneurysm at the Presurgical Stage.

Background: Whether drug therapy slows the growth of abdominal aortic aneurysms (AAAs) in the Japanese population remains unknown. Methods and Results: In a multicenter prospective open-label study, patients with AAA at the presurgical stage (mean [±SD] AAA diameter 3.27±0.58 cm) were randomly assigned to treatment with candesartan (CAN; n=67) or amlodipine (AML; n=64) considering confounding factors (statin use, smoking, age, sex, renal function), with effects of blood pressure control minimized setting a target control level. The primary endpoint was percentage change in AAA diameter over 24 months. Secondary endpoints were changes in circulating biomarkers (high-sensitivity C-reactive protein [hs-CRP], malondialdehyde-low-density lipoprotein, tissue-specific inhibitor of metalloproteinase-1, matrix metalloproteinase [MMP] 2, MMP9, transforming growth factor-ß1, plasma renin activity [PRA], angiotensin II, aldosterone). At 24 months, percentage changes in AAA diameter were comparable between the CAN and AML groups (8.4% [95% CI 6.23-10.59%] and 6.5% [95% CI 3.65-9.43%], respectively; P=0.23]. In subanalyses, AML attenuated AAA growth in patients with comorbid chronic kidney disease (CKD; P=0.04) or systolic blood pressure (SBP) <130 mmHg (P=0.003). AML exhibited a definite trend for slowing AAA growth exclusively in never-smokers (P=0.06). Among circulating surrogate candidates for AAA growth, PRA (P=0.02) and hs-CRP (P=0.001) were lower in the AML group. Conclusions: AML may prevent AAA growth in patients with CKD or lower SBP, associated with a decline in PRA and circulating hs-CRP.

Rehabilitation contributes to lower readmission rates for individuals with peripheral arterial disease: A retrospective observational study.

BACKGROUND: Non-pharmacological interventions, such as rehabilitation, are crucial for the treatment of people with peripheral arterial disease (PAD). Although several studies have shown rehabilitation is effective in improving the functional prognosis of PAD, there is currently insufficient evidence regarding its effect on readmission rates. OBJECTIVES: To examine the impact of rehabilitation on readmission rates for people with PAD. METHODS: A retrospective analysis of the JMDC hospital database was performed on data from two groups of people aged ≥20 years who were hospitalized between 2014 and 2020 with PAD, as based on a previous diagnosis. Participants were divided according to whether they did, or did not, receive any form of rehabilitation as part of their treatment in hospital. The primary outcome was readmission rates at 30, 60, 90, and 180 days after initial admission. A one-to-one propensity score matching was used to compare readmission rates between rehabilitation and non-rehabilitation groups. RESULTS: We included 13,453 people with PAD, of whom 2701 pairs (5402 subjects) were selected after being matched in the rehabilitation and non-rehabilitation groups. The rehabilitation group participants had significantly lower mortality and readmission rates at 30, 60, 90, and 180 days. The odds ratios (95% confidence interval) for both groups were 0.79 (0.69-0.91; 30 days), 0.81 (0.71-0.91; 60 days), 0.78 (0.69-0.88; 90 days), and 0.79 (0.71-0.88; 180 days). CONCLUSIONS: This large, nationwide study found that rehabilitation treatment during hospitalization was associated with lower readmission rates and mortality for people following hospitalization with PAD and supports its inclusion as a standard PAD treatment.

Different voltage dependence of ICaL blockade in nonselective IKr blockers causes their opposite effects on early afterdepolarization in drug-induced arrhythmia.

Several false-positive results in the human ether-à-gogo-related gene test suggest that blockers of the rapid component of delayed rectifier K+ current (IKr) do not necessarily produce drug-induced arrhythmias. Specifically, the occurrence of early afterdepolarization (EAD) differs among IKr blockers, even if the prolonged action potential duration is in the same range. To predict EAD in drug-induced arrhythmias, we proposed a prediction method based on the mechanisms underlying the difference in frequency of EAD among nonselective IKr blockers. The mechanisms were elucidated by examining how different blockade kinetics of L-type Ca2+ current (ICaL) affect the frequency of EAD, using mathematical models of human ventricular myocytes. Addition of voltage-independent ICaL blockade resulted in the suppression of EAD. However, when voltage-dependent ICaL blockade kinetics of amiodarone, bepridil, and terfenadine were incorporated into ICaL in the model, bepridil and terfenadine induced EAD more than the voltage-independent ICaL blockade, while amiodarone suppressed EAD more effectively. Opposite effects were accounted for by the difference in ICaL blockade at negatively polarized potential. EAD occurrence was found to be associated with ICaL blockade measured at -20 mV. These results suggest that voltage dependence of ICaL blockade may be useful in predicting the different risks of nonselective IKr blockers.

Clinical outcomes following percutaneous coronary intervention for bifurcation lesions: kissing balloon inflation vs. sequential dilation.

Percutaneous coronary intervention for bifurcation lesions remains challenging, with there being several debatable issues, including the requirement for kissing balloon inflation (KBI). The objective of this study was to assess the clinical outcomes following single crossover stent implantation with KBI or sequential dilation alone. Data were examined for 255 non-left main bifurcation lesions (246 patients) treated with single crossover stent implantation, followed by side branch (SB) strut dilation with KBI (n = 74 lesions) or sequential dilation (n = 181 lesions) in three hospitals. Target lesion revascularization (TLR) was the primary endpoint. There was no significant difference in the pre-procedural reference diameter of both the main vessel (MV) and SB between the KBI and sequential dilation groups. However, MV post-dilation balloon size was smaller with lower pressure and post-procedural minimal lumen diameter was significantly smaller in the KBI group. During the median follow-up period of approximately 3 years, TLR incidence was significantly higher in the KBI group than in the sequential dilation group; in particular, the TLR rate at the distal MV was higher in the former. For bifurcation lesions treated with single crossover stent implantation, the TLR rate was higher after KBI than after sequential dilation; this was mainly due to higher revascularization in the distal MV. For bifurcation lesions treated with KBI, MV post-dilation balloon diameter tended to be smaller with lower pressure, which might lead to poorer stent expansion and a higher TLR rate.

Association Between Sarcopenic Obesity and Metabolic Syndrome in Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: In the last two decades, a new phenotype termed Sarcopenic Obesity (SO), in which sarcopenia and obesity coexist, has emerged. OBJECTIVE: The aim of this systematic review and meta-analysis was first to assess the prevalence of Metabolic syndrome (Mets) among individuals with and without SO, and second, to determine if SO may increase the relative risk of Mets. METHODS: This study was conducted in adherence to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and the data were collated by means of metaanalysis and narrative synthesis. RESULTS: Twelve studies including a total of 11,308 adults with overweight or obesity of both genders met the inclusion criteria and were reviewed, revealing two main findings. First, a similar overall prevalence of Mets in individuals with SO (61.49%; 95% CI: 52.19-70.40) when compared to those without SO (56.74%; 95% CI: 47.32-65.93) was identified. Second, the presence of SO appears not to increase the risk of Mets with respect to those without SO (RR = 1.08, 95% CI: 0.99- 1.17, p = 0.07). CONCLUSION: No higher prevalence of Mets among individuals with SO when compared to those with obesity only, nor a significant association between SO and a higher risk of Mets was found.

How successful are we in relieving terminal dyspnea in cancer patients? A real-world multicenter prospective observational study.

PURPOSE: Parenteral morphine is widely used for dyspnea of imminently dying cancer patients, but the outcomes to expect over time remain largely unknown. We examined outcomes after the administration of parenteral morphine infusion over 48 h in cancer patients with a poor performance status. METHODS: This was a multicenter prospective observational study. Inclusion criteria were metastatic/locally advanced cancer, ECOG performance status = 3-4, a dyspnea intensity ≥ 2 on a Support Team Assessment Schedule, Japanese version (STAS-J), and receiving specialized palliative care. After initiating parenteral morphine infusion, we measured dyspnea STAS-J as well as Memorial Delirium Assessment Scale (MDAS), item 9, and Communication Capacity Scale (CCS), item 4, every 6 h over 48 h. RESULTS: We enrolled 167 patients (median survival = 4 days). The mean age was 70 years, 80 patients (48%) had lung cancer, and 109 (65%) had lung metastases. The mean STAS-J scores decreased from 3.1 (95% confidence interval (CI) = 3.0-3.2) at the baseline to 2.1 (95%CI = 1.9-2.2) at 6 h, and remained 1.6-1.8 over 12-48 h. The proportion of patients with dyspnea relief (STAS-J ≤ 1) increased to 39% at 6 h, and ranged between 49 and 61% over 12-48 h. In contrast, up to 6.6 and 20% of patients showed hyperactive delirium (MDAS item 9 ≥ 2) and an inability to communicate (CCS item 4 = 3), respectively, over 48 h. CONCLUSIONS: Overall, terminal dyspnea was relatively well controlled with parenteral morphine, though a significant number of patients continued to suffer from dyspnea. Future efforts are needed to improve outcomes following standardized dyspnea treatment using patient-reported outcomes for imminently dying patients.

An experiment to classify the clinical fear seen during aerobic movement acquisition in adults with visual impairment.

[Purpose] This study aimed to classify the fear that occurs during the process of a squat-like movement by persons with visual impairment. [Subjects and Methods] Fifteen persons with a visual impairment, 45 years and older, who were independent in daily living were recruited for the study. The study utilized a field experiment design. The setting was the Kusatsumachi Welfare Center, and the study period was from March through August 2015. Outcome measures included the presence or absence of fear during attempt of a squat-like movement on a force plate. Metrics included the ratio of low and high frequency components of heart rate variability spectra (cm2/Hz) based on resting rate intervals (ActiGraph wGT3X-BT, USA). Autonomic hyperactivity was defined as the occurrence of objective fear with LF/HF ratio of over 2.0. Statistics included Fischer's exact test. [Results] Four fear types included the combination of danger and objective fear factors. The frequencies of occurrence of clinically categorized subjective fear across the four fear types were two (danger, fear), seven (no danger, fear), six (danger, no fear), and zero (no danger, no fear) persons. [Conclusion] This procedure of classifying fear might be feasible during evaluation of a squat-like movement by persons with a visual impairment.

Validity of body impedance analysis for evaluating body composition in patients undergoing long-term hemodialysis.

[Purpose] This study assessed changes in body composition before and after dialysis in chronic hemodialysis patients and determined the relationships between various body composition parameters and blood lipid levels in these patients. [Subjects] The cross-sectional study included 19 dialysis outpatients (17 men and 2 women, aged 35-82 years). [Methods] Body mass index, body weight, percent body fat, and percent skeletal muscle were measured before and after dialysis by using body impedance analysis. Blood lipid levels were obtained from patients' clinical records. The body composition parameters before and after dialysis were compared using paired t-tests. Spearman's rank correlation coefficients were calculated to determine relationships between the body composition parameters, before and after dialysis, and the blood lipid levels. [Results] All body composition parameters differed significantly before and after dialysis. High-density lipoprotein cholesterol level significantly correlated with all the body composition parameters, whereas total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels significantly correlated with some of these parameters. The correlation coefficients revealed no major differences in the relationships between blood lipid parameters and body compositions before and after dialysis. [Conclusion] Our findings suggest that body composition parameters, whether measured before or after dialysis, can be used to evaluate obesity in longitudinal studies.

Non-superiority of Kakkonto, a Japanese herbal medicine, to a representative multiple cold medicine with respect to anti-aggravation effects on the common cold: a randomized controlled trial.

OBJECTIVE: Kakkonto, a Japanese herbal medicine, is frequently used to treat the common cold not only with a physician's prescription, but also in self-medication situations. This study aimed to examine whether Kakkonto prevents the aggravation of cold symptoms if taken at an early stage of illness compared with a well-selected Western-style multiple cold medicine. METHODS: This study was a multicenter, active drug-controlled, randomized trial. Adults 18 to 65 years of age who felt a touch of cold symptoms and visited 15 outpatient healthcare facilities within 48 hours of symptoms onset were enrolled. The participants were randomly assigned to two groups: one treated with Kakkonto (Kakkonto Extract-A, 6 g/day) (n=209) and one treated with a Western-style multiple cold medicine (Pabron Gold-A, 3.6 g/day) (n=198) for at most four days. The primary outcome of this study was the aggravation of cold, nasal, throat or bronchial symptoms, scored as moderate or severe and lasting for at least two days within five days after entry into the study. RESULTS: Among the 410 enrollees, 340 (168 in the Kakkonto group and 172 in the Pabron group) were included in the analyses. The proportion of participants whose colds were aggravated was 22.6% in the Kakkonto group and 25.0% in the Pabron group (p=0.66). The overall severity of the cold symptoms was not significantly different between the groups. No harmful adverse events occurred in either group. CONCLUSION: Kakkonto did not significantly prevent the progression of cold symptoms, even when prescribed at an early stage of the disease.

Smoking as a confounding factor on the influence of cold therapy on the vascular endothelium function of young men.

[Purpose] This study was designed to determine whether smoking affects endothelium function after cold therapy in young men. [Subjects] The final cohort included 27 healthy men (age, 20-21 years). Because an impact on vascular endothelium function was anticipated to be caused by smoking, the study enrolled 14 participants in a smoking group and 13 in a non-smoking group. [Methods] Vascular endothelial function was assessed by determining the reactive hyperemia index (RHI), using finger-tonometry. RHI was measured twice, at rest (baseline) and after a cold stimulus. The forearm was cooled with an ice bag for 10 min as the cold stimulus. Comparisons between the RHI at baseline and after cold treatment, and between the smoking and non-smoking groups, were performed using the paired and unpaired t-tests, respectively. [Results] There was a significant difference in baseline RHI values between the smoking and non-smoking groups, but there was no significant difference between the baseline and post-treatment RHI values in either group. [Conclusion] These results suggest that cigarette smoking damages the endothelial cells in young men with a short history of smoking. However, cold therapy did not have a significant impact on the RHI in either group.

A bioluminescent assay system for whole-cell determination of hormones.

A bioluminescent-assay system was fabricated for an efficient determination of bioactive small molecules in physiological samples. The following three components were newly created for this assay system: (i) a single-chain probe exerting a 7.2-times stronger optical intensity than conventional ones, (ii) a high throughput assay device uniquely designed for the assay system with ca. one-fourth smaller standard deviation (S.D.) to samples than without the device, (iii) a buffer cocktail optimized for the assay system. The advantages of the assay system were evaluated by determining (i) the stress hormone levels in human saliva and (ii) multicolor imaging of genomic and nongenomic effects of woman sex hormones. This study guides on how to fabricate an efficient assay system for bioactive small molecules with convenience and high precision.

Phase-transfer behavior of cross-linked poly(acrylic acid) particles prepared by dispersion polymerization from ionic liquid to water.

The phase-transfer behavior of poly(acrylic acid) (PAA) particles from the hydrophobic ionic liquid N,N-diethyl-N-methyl-N-(2-methoxyethyl)ammonium bis(trifluoromethanesulfonyl)amide phase to the water phase in the particle state, which we reported previously, was examined in more detail. PAA particles were prepared in the ionic liquid 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amide ([Bmim][TFSA]) and the organic solvent chloroform and were extracted. The transfer of PAA particles to water in the particle state was also observed in [Bmim][TFSA] systems. In contrast, the transfer phenomenon was not observed in the chloroform system. It was clarified that water/oil interfacial tension γ(wo) is an important parameter in the extraction of PAA in the particle state from the viewpoint of free energy. When the cationic surfactant tetradecyltrimethylammonium bromide, aqueous solution was used as the extraction medium, the PAA particles were extracted in the particle state from chloroform to water, in which γ(wo) became as low as that of the ionic liquid. This suggests that the phase-transfer phenomenon of PAA particles in the particle state was induced by the ionic liquid's unique property of low interfacial tension with water despite its high hydrophobic character.

Determination of oxygen sources for oxidation of benzene on TiO2 photocatalysts in aqueous solutions containing molecular oxygen.

Photocatalytic oxidation of benzene to CO(2) was studied in aqueous solutions using different kinds of TiO(2) powders, and isotopic oxygen tracers (H(2)(18)O and (18)O(2)) were used to investigate the oxidation process. Phenol was produced as a main intermediate in solution. When anatase powders, which showed high activity for oxidation of benzene, were used, 70-90% of oxygen introduced into phenol was from water. On the other hand, when rutile powders were used, only 20-40% of the oxygen was from water. The rest was from molecular oxygen in both cases. The rate of phenol production by using molecular oxygen was nearly the same between anatase and rutile powders. Hence, the high activity of anatase powders for oxidation of benzene to CO(2) is attributed to their high activity for oxidation of benzene to phenol, which is considered to be the rate-determining step, using water as the oxygen source. The processes using water and molecular oxygen as the oxygen sources are ascribed, respectively, to oxygen transfer and hole transfer processes in the initial step of benzene oxidation.

Preparation of poly(acrylic acid) particles by dispersion polymerization in an ionic liquid.

Poly(acrylic acid) (PAA) particles were successfully prepared by dispersion polymerization of acrylic acid in ionic liquid, N,N-diethyl-N-methyl-N-(2-methoxyethyl)ammonium bis(trifluoro-methanesulfonyl)amide ([DEME][TFSA]) at 70 degrees C with low hydrolysis grade (35.4%) poly(vinyl alcohol) as stabilizer. Interestingly, the PAA particles were easily extracted as particle state with water. Thus, the PAA particles had a cross-linked structure during the polymerization without cross-linker. Moreover, it was also noted that the cross-linking density of the PAA particles could be controlled by thermal treatment at various temperatures in [DEME][TFSA] utilizing the advantages of nonvolatility and high thermal stability of the ionic liquid.

Effect of genetic predisposition on the risk of gallbladder cancer in Hungary.

A CYP1A1 polymorphism has been associated with an increased risk for gallbladder cancer (GBC) in Japanese women. However, genetic risk factors for GBC in Hungary, where the population has a relatively high GBC incidence, has not been well studied. We therefore tested associations between CYP1A1 T3801C, CYP1A1 Ile462Val, GSTM1deletion, and TP53 Arg72Pro and GBC in Hungary. Genomic DNA was extracted from peripheral blood of 100 controls (52 men and 48 women) and from the tissue embedded in paraffin of 43 cases (6 men and 37 women). The case-control analysis was limited to females due to a small number of males. Of 37 female cases, 21 (56.8%) were diagnosed as adenocarcinoma, and the remaining 16 (43.2%) were classified as non-adenocarcinoma. The odds ratios (ORs) for the Ile/Val genotype and the Val allele were 8.9 (95% CI: 2.9-27.4) and 4.4 (95% CI: 1.7-11.1), respectively. The occurrence of the combined variant genotypes of CYP1A1 Ile462Val and GSTM1 (37.8% vs. 8.3%) or CYP1A1 Ile462Val and TP53 Arg72Pro (24.3% vs. 0%) was significantly higher in the cases than in the controls. The Ile/Val genotype was significantly associated with an increased risk of adenocarcinoma (OR 9.2; 95% CI: 2.6-32.6) and non-adenocarcinoma (OR 8.4; 95% CI: 2.2-32.4). Additionally, the Arg/Pro genotype increased risk of non-adenocarcinoma (OR 3.8; 95% CI: 1.2-12.8). The Val allele may contribute to the development of GBC not only in Japanese but also in Hungarian women. Our results provide a rationale for further studies of genetic variation on the risk of GBC in Hungary.

A pilot study of advice on physical activity in senior disabled individuals in rural Japan.

This study evaluates the effect of active implementation of the amount of physical activity on the double product (DP) in senior disabled individuals. Our study included 20 hemiplegic patients comprising an intervention group (IG; n = 10) who performed prescribed exercises daily for 12 weeks and a control group (CG; n = 10) for whom physical activity (PA) was measured without intervention. In the IG, the energy consumption during PA with multiple positions and intensity increased significantly as compared to that of the CG. In the IG0 to the CG, the DP decreased significantly. We concluded that advice regarding active implementation increases the amount of PA and improves the DP after a 12-week period.

Ropivacaine-induced toxicity with overdose suspected after axillary brachial plexus block.

Ropivacaine has a high threshold for systemic toxicity. We report and highlight a rare case in which an overdose of ropivacaine was suspected of leading to a generalized convulsion following the injection of this agent for axillary brachial plexus block (ABPB). A 25-year-old woman (height, 153 cm; weight, 48 kg; American Society of Anesthesiologists physical status I) was scheduled for finger surgery with ABPB. The perivascular sheath was identified by fascial clicks. We administered 300 mg (6.25 mg x kg(-1)) ropivacaine, while confirming that no blood flow was observed in the injection line by repeated negative aspiration tests. Ten minutes after the injection, most sensory and motor nerves were blocked effectively. Thirteen minutes after the administration, the patient lost consciousness and convulsed suddenly. No severe symptoms of cardiovascular toxicity occurred. The concentration of ropivacaine in a venous blood sample taken 28 min after the ropivacaine injection was 3.65 microg x ml(-1). She recovered with no sequelae. Limited cases have indicated high efficacy and sufficient safety for the use of 300 mg ropivacaine for ABPB. However, the toxic threshold of ropivacaine remains unclear, and the dose should be calculated in relation to the weight of the patient to prevent severe toxic complications.