Olfactory and taste dysfunctions caused by COVID-19: a nationwide study.

BACKGROUND: Olfactory dysfunctions (OD) and taste dysfunctions (TD) are widely recognized as characteristic symptoms of COVID-19; however, the frequency and mode of occurrence has varied depending on the viral mutation. The prevalence and characteristics of OD/TD in Japan have not been definitively investigated. The purpose of this study is to assess the prevalence of OD/TD in Japan during the Alpha variant epidemic, and measure symptom prolongation at 6 months and 1 year later following initial infection. METHODS: Patients treated for COVID-19 between February to May 2021 were evaluated for OD/TD symptoms and provided with a QOL questionnaire. Olfactory tests and taste tests were performed using Open Essence and Taste Strips, respectively. RESULTS: Among the 251 COVID-19 patients who participated, 119 underwent both olfactory and taste tests. Prevalence of subjective OD and TD at the time of survey was 57.8% and 40.2%, respectively. After 12 months, the prevalence fell to 5.8% for OD and 3.5% for TD. Among the OD/TD patients, 36.6% experienced parosmia, and 55.4% experienced parageusia. Prevalence of parosmia and parageusia was higher at 6 and 12 months than at the time of survey. Patients with long-lasting disease reported qualitative dysfunctions and scored significantly higher in food-related QOL problems. Most patients who were aware of their hyposmia had low scores on the olfactory test (83.1%). In contrast, only 26.7% of patients who were aware of their hypogeusia had low scores on the taste test. CONCLUSIONS: The prevalence of COVID-19-related OD and TD at the time of survey was 57.8% and 40.2%, respectively. Subjective symptoms of OD and TD persisted for one year in 5.8% and 3.5% of patients, respectively. More than half of the patients with OD or TD complained of qualitative dysfunction and a decrease in their QOL related to eating and drinking. Most patients with TD did not have true TD, but rather developed flavour disorders associated with OD. This conclusion is supported by the finding that patients with subjective OD had low scores on the olfactory test, whereas most patients with subjective TD had normal scores on the taste test.

Observation of a large reaction cross section in the drip-line nucleus 22C.

Reaction cross sections (sigma(R)) for 19C, 20C and the drip-line nucleus 22C on a liquid hydrogen target have been measured at around 40A MeV by a transmission method. A large enhancement of sigma(R) for 22C compared to those for neighboring C isotopes was observed. Using a finite-range Glauber calculation under an optical-limit approximation the rms matter radius of 22C was deduced to be 5.4+/-0.9 fm. It does not follow the systematic behavior of radii in carbon isotopes with N < or = 14, suggesting a neutron halo. It was found by an analysis based on a few-body Glauber calculation that the two-valence neutrons in 22C preferentially occupy the 1s(1/2) orbital.

Poor applicability of estimation method for adults to calculate unbound serum concentrations of valproic acid in epileptic neonates and infants.

OBJECTIVE: To characterize the relationship between total and unbound concentrations of valproic acid (VPA) in epileptic neonates and infants, the clinical examination records of those patients archived via therapeutic drug monitoring (TDM) activities were retrospectively analyzed. METHODS: The screening encompassed 249 records of 114 epileptic patients aged 0-19 years old, who were treated with VPA monotherapy and whose total and unbound VPA concentrations were determined. These data were divided into groups according to the patients' age. In each group, the relationship between total and unbound VPA concentrations was compared to a reference profile, and the deviation from the reference was evaluated. The reference profile was calculated using the Langmuir equation, in which two parameters Kd and Bm were set to 7.8 and 130 microg/mL, respectively, according to our previous findings. RESULTS: The relationship between total and unbound VPA concentrations of patients of 0 years old considerably deviated from the reference, and their unbound VPA concentrations were generally higher compared to the corresponding reference values. It is suggested that the large deviation is related to the fact that the serum albumin concentrations of patients younger than 1 year old tend to be lower than those of patients in other age groups. CONCLUSION: Since the relationship between the VPA concentrations of epileptic neonates and infants is noticeably different from the reference, the unbound serum VPA concentrations of these patients are not adequately estimated using the same method as that for grown-ups. The unbound VPA concentrations of neonates and infants should be explicitly determined via TDM activities.

Randomized clinical trial of single skin sterilization with a povidone-iodine applicator versus conventional skin sterilization in abdominal surgery.

Background: The efficacy of widely used povidone-iodine applicators for skin sterilization in abdominal surgery is unclear. The aim of this trial was to evaluate whether sterilization with a povidone-iodine applicator was not inferior to a conventional sterilization method. Methods: Patients undergoing elective abdominal surgery were assigned randomly to receive single sterilization with the applicator or conventional sterilization. The primary endpoint was wound infection rate. Secondary endpoints were rate of organ/space surgical-site infection (SSI), adverse effects of povidone-iodine, amount of povidone-iodine used and total cost of sterilization. Results: Of 498 patients eligible for the study between April 2015 and September 2017, 240 were assigned and analysed in the applicator group and 246 in the conventional group. Wound infection was detected in 16 patients (6·7 per cent) in the applicator group and 16 (6·5 per cent) in the conventional group (absolute difference 0·0016 (90 per cent c.i. -0·037 to 0·040) per cent; P = 0·014 for non-inferiority). There was no difference between the groups in the organ/space SSI rate (11 patients (4·6 per cent) in the applicator group and 16 (6·5 per cent) in the conventional group. Both the amount of povidone-iodine used and the total cost of sterilization were higher in the conventional group than in the applicator group (median 76·7 versus 25 ml respectively, P < 0·001; median €7·0 versus €6·4, P < 0·001). Skin irritation was detected in three patients in the conventional group. Conclusion: In abdominal surgery, this povidone-iodine applicator was not inferior to conventional sterilization in terms of the wound infection rate, and it is cheaper. Registration number: UMIN000018231 (http://www.umin.ac.jp/ctr/).

Characterization of non-linear relationship between total and unbound serum concentrations of valproic acid in epileptic children.

OBJECTIVE: To establish a regression equation to properly estimate the unbound serum concentration of valproic acid (VPA) from its total serum concentration; the relationship between total and unbound serum VPA concentrations was retrospectively characterized. METHODS: Data were obtained from the clinical examination records that were routinely archived during therapeutic drug monitoring. The screening encompassed 342 records of 108 paediatric patients whose total and unbound VPA concentrations had been determined. The relationship between total and unbound VPA concentrations was characterized according to the Langmuir equation by taking account of inter-individual variability with the nonmem program. RESULTS: The total VPA concentration (C(t)) in the screened patients ranged from 5.5 to 179.8 microg/mL, and the unbound VPA concentration (C(f)) increased in a non-linear manner as the total VPA concentration increased. Taking account of the effects of antiepileptics concurrently administered, the VPA dissociation constant (K(d)) and maximum binding site concentration (B(m)) were 7.8 +/- 0.7 and 130 +/- 4.5 microg/mL respectively, for the regression equation, C(t) = C(f) + B(m) x C(f)/(K(d) + C(f)). An alteration in the unbound concentration was seen in patients who were treated with the combination of VPA and ethosuximide and in those who received two additional antiepileptics. CONCLUSIONS: A regression equation for estimation of the unbound VPA concentration, based on total VPA concentration collected during routine therapeutic drug monitoring was established. Use of two additional antiepileptics and ethosuximide treatment was considered as potential factors affecting unbound VPA concentration.

Comparison between dexmedetomidine and midazolam as a sedation agent with local anesthesia in inguinal hernia repair: randomized controlled trial.

PURPOSE: In Japan, inguinal hernia repair is widely performed with local anesthesia. The objective of this study was to evaluate safety and efficacy of intravenous dexmedetomidine as a sedation agent with local anesthesia in inguinal hernia repair. METHODS: We performed this randomized, single-blind study for 200 patients who were scheduled to undergo inguinal hernia repair with local anesthesia. Patients were randomly divided into two groups (dexmedetomidine group: Group D, midazolam group: Group M). The primary outcome was to evaluate the safety of intravenous dexmedetomidine. Secondary outcomes were to analyze results of operators' surveys and patients' questionnaires and evaluate implementation of conscious sedation. RESULTS: Incidence of respiratory depression was significantly higher in Group M than Group D (p = 0.03). Other adverse events examined did not differ significantly. All three operators' questionnaires indicated that results were better in Group D than Group M. More than 70% of patients in both groups were satisfied with the surgery. More than 80% of Group D patients and 74% of Group M patients achieved a state of conscious sedation. CONCLUSION: This study demonstrated that intravenous dexmedetomidine during hernia repair with local anesthesia is safe and the results were satisfactory to both operators and patients.

Endocrine and morphological study of a clinically silent somatotroph adenoma of the human pituitary.

Silent somatotroph adenomas are defined as tumors showing morphological features consistent with GH production, but no clinical evidence of GH excess. We report here the case of a 46-yr-old woman with a large pituitary macroadenoma, slightly elevated serum GH levels, high serum insulin-like growth factor-I levels, and abnormal GH dynamics, but no acromegaly. The endocrinological abnormalities receded after transphenoidal surgery despite tumor persistence, as shown by neuroimaging. The reverse hemolytic plaque assay, performed for the first time in a silent GH cell adenoma, demonstrated that the number of GH cells releasing GH and the amount of GH discharged from individual cells were less than those in clinically functioning somatotroph adenomas. Thus, it is conceivable that this tumor secreted only small quantities of GH and for only short periods, providing an explanation for the lack of acromegaly. It appears that silent somatotroph adenomas do not represent a distinct entity. It is more likely that there is a continuous spectrum from clinically functioning, sparsely granulated somatotroph adenomas with high serum GH levels to silent somatotroph adenomas with normal serum GH levels. The cause of the lack of GH oversecretion in silent GH cell adenomas has yet to be elucidated.

Calcium sensitivity of contractile proteins from chicken gizzard muscle.

Actin, myosin, and "native" tropomyosin (NTM) were separately isolated from chicken gizzard muscle and rabbit skeletal muscle. With various combinations of the isolated contractile proteins, Mg-ATPase activity and superprecipitation activity were measured. It was thus found that gizzard myosin and gizzard NTM behaved differently from skeletal myosin and skeletal NTM, whereas gizzard actin functioned in the same wasy as skeletal actin. It was also found that gizzard myosin preparations were often Ca-sensitive, that is, that the two activities of gizzard myosin plus actin without NTM were activated by low concentrations of Ca2+. The Mg-ATPase activity of a Ca-insensitive preparation of gizzard myosin was not activated by actin even in the presence of Ca2+. When Ca-sensitive gizzard myosin was incubated with ATP (and Mg2+) in the presence of Ca2+, a light-chain component of gizzard myosin was phosphorylated. The light-chain phosphorylation also occurred when Ca-insensitive myosin was incubated with gizzard NTM and ATP (plus Mg2+) in the presence of Ca2+. In either case, the light-chain phosphorylation required Ca2+. Phosphorylated gizzard myosin in combination with actin was able to exhibit superprecipitation, and Mg-ATPase of the phosphorylated gizzard myosin was activated by actin; the actin activation and superprecipitation were found to occur even in the absence of Ca2+ and NTM or tropomyosin. The phosphorylated light-chain component was found to be dephosphorylated by a partially purified preparation of gizzard myosin light-chain phosphatase. Gizzard myosin thus dephosphorylated behaved exactly like untreated Ca-insensitive gizzard myosin; in combination with actin, it did not superprecipitate either in the presence of Ca2+ or in its absence, but did superprecipitated in the presence of NTM and Ca2+. Ca-activated hydrolysis of ATP catalyzed by gizzard myosin B proceeded at a reduced rate after removal of Ca2+ (by adding EGTA), whereas that catalyzed by a combination of actin, gizzard myosin, and gizzard NTM proceeded at the same rate even after removal of Ca2+. However, addition of a partially purified preparation of gizzard myosin light-chain phosphatase was found to make the recombined system behave like myosin B. Based on these findings, it appears that myosin light-chain kinase and myosin light-chain phosphatase can function as regulatory proteins for contraction and relaxation, respectively, of gizzard muscle.

Growth hormone and prolactin gene expression in human densely and sparsely granulated somatotroph adenomas by in situ hybridization with digoxigenin-labeled probes.

We studied growth hormone (GH) and prolactin (PRL) messenger ribonucleic acids (mRNAs) in 14 cases with densely granulated somatotroph (DG) adenomas and 10 cases with sparsely granulated somatotroph (SG) adenomas using in situ hybridization with digoxigenin-labeled probes and correlated these data with their immunohistochemical results. A good correlation between in situ hybridization results and immunohistochemical data was found in most cases examined. The DG adenomas generally had a diffuse and intense GH immunoreactivity and GH hybridization signal, whereas in SG adenomas the number of cells exhibiting a GH mRNA signal and the strength of the GH mRNA signal in these cells were relatively lower than those of DG adenomas, indicating that lower expression of the GH mRNA signal is responsible for lower GH production in SG adenomas. In addition, PRL mRNA expression differed in the two types of adenoma; in DG adenomas, seven cases (50%) expressed PRL mRNA signal with a focal or scattered distribution despite normal serum PRL levels, but two showed no PRL immunoreactivity. In contrast, in SG adenomas, only one case contained a few cells possessing a PRL mRNA signal despite having no PRL immunoreactivity. It can be concluded that DG and SG adenomas, which have been considered variants of the same tumor, display definite differences as to GH or PRL gene expression in each type of adenoma.

Unusual CT and MR findings of inflammatory pseudotumor in the parapharyngeal space: case report.

Unusual MR and CT findings of an inflammatory pseudotumor in the parapharyngeal space of a 73-year-old woman are reported. The mass was hypointense on T1- and T2-weighted images and demonstrated ring enhancement after contrast medium injection. Punctated calcifications were scattered at the periphery. Inflammatory pseudotumors in the parapharyngeal space are rare, and only three cases have been reported. The possible pathogenesis and varieties of inflammatory pseudotumors are discussed.

Enterogenous cyst of the cerebellopontine angle cistern: case report.

A case of an enterogenous cyst located in the cerebellopontine angle cistern is presented. These cysts have usually been found in the spinal canal, and their intracranial occurrence is exceptional. In the present case, the cyst was lined histologically by a single epithelial layer of cuboidal cells with some glandular structures resembling the fundic glands of the stomach. The unusual location of the cyst and its histological features are discussed.

Early and late postoperative hearing preservation in patients with acoustic neuromas.

OBJECTIVE: To examine the incidence of postoperative hearing preservation and the factors that influence early and late postoperative hearing in patients with acoustic neuromas. METHODS: We reviewed the results of surgery and follow-up in 73 consecutive patients. RESULTS: Of 73 patients, 51 demonstrated preoperative hearing levels equal to or better than Class 3, according to the classification system of Gardner and Robertson (8). After surgery, 21 (41.2%) of the 51 patients retained Class 1, 2, or 3 hearing. Hearing was more likely to be preserved after surgery if the tumor was small and if the preoperative hearing was good. The early postoperative hearing grade declined in 7 (33.3%) of the 21 patients, compared with the preoperative hearing level. The long-term follow-up of 17 patients in whom measurable hearing was retained after surgery indicated that 3 (17.6%) experienced delayed worsening of hearing, without evidence of tumor recurrence. The extent of hearing loss in patients with successful hearing preservation was not correlated with tumor size, preoperative hearing, patient age, or the shape of the cochlear nerve on the tumor surface. Hearing at long-term follow-up was significantly better in patients with excellent preoperative hearing. CONCLUSION: Postoperative long-term preservation of hearing is more likely if surgery is performed while the tumor is still small and hearing is still excellent. Under these circumstances, it is more likely that the early and late hearing loss will be compensated.

Creutzfeldt-Jakob disease transmitted by a cadaveric dura mater graft.

We report a case of Creutzfeldt-Jakob disease developing in a 31-year-old woman 56 months after she received a cadaveric dura mater graft after the removal of a giant pituitary adenoma. Creutzfeldt-Jakob disease was confirmed by a brain autopsy and the existence of an abnormal isoform of prion protein, verified by both immunohistochemical and Western blot analysis. Moreover, prion protein gene analysis was shown in this case to possess a wild-type genotype. The characteristics of Creutzfeldt-Jakob disease after a cadaveric dura mater graft are reviewed and discussed.

Growth hormone-producing pituitary adenomas: correlations between clinical characteristics and morphology.

In this study, we compared the clinical and endocrinological characteristics, neuroimaging findings, surgical outcome, and conventional histological findings (including immunohistochemistry) with the electron microscopic appearance of 31 growth hormone (GH)-producing adenomas. By electron microscopy, these 31 tumors were divided into 23 densely granulated somatotroph adenomas (DG adenomas) and 8 sparsely granulated somatotroph adenomas (SG adenomas). SG adenomas more frequently affected younger women, but no significant correlation was found between the adenoma type and the characteristic signs and symptoms of acromegaly, the incidence of diabetes mellitus or hypertension, or the basal serum GH and insulin-like growth factor I levels. A distinct response of GH to thyrotropin-releasing hormone, bromocriptine, or GH-releasing hormone was significantly more common in patients with DG adenomas than in those with SG adenomas, whereas the incidence of a response to gonadotropin-releasing hormone or oral glucose was not significantly different between the two groups. An analysis of neuroimaging findings and surgical results indicated that SG adenomas were more likely to be macroadenomas with suprasellar extension or invasive tumors and had a lower surgical cure rate. However, postoperative radiotherapy seemed to be similarly effective in both types of adenoma to prevent a tumor recurrence and to reduce postoperative GH basal level in serum. Light microscopy showed that DG adenomas were mainly acidophilic and were immunopositive not only for GH but also for prolactin (43%), the beta subunit of thyroid-stimulating hormone (26%), and the alpha subunit of glycoprotein hormone (87%), whereas SG adenomas were almost all chromophobic and only revealed immunopositivity for GH.(ABSTRACT TRUNCATED AT 250 WORDS)

Gonadotroph adenoma of the pituitary mimicking a prolactinoma.

In a 41-year-old woman with mild hyperprolactinemia and amenorrhea, preoperative hormonal and neuroradiological findings suggested the diagnosis of a macroprolactinoma. She underwent transsphenoidal surgery since the tumor size had not changed in spite of bromocriptine administration for 5 months. Consequently, this case was diagnosed as a female-type gonadotroph adenoma on the basis of its characteristic ultrastructural features including a honeycomb Golgi complex, even though endocrinological and immunohistochemical findings were not those of a typical gonadotroph adenoma.

The spatiotemporal range of inhibitory interaction in flicker detection.

The flicker thresholds of luminous bars were measured as a function of the spatial and/or temporal separation of two flickering stimuli. Each of the bars had an intensity profile of one-half cycle of a sinusoidal wave subtending 2.26 x 0.45 arc deg and each bar was presented twice at two positions with a duration of 10 msec. The spatial separation was defined as the distance between the adjacent flanks of two flickering stimuli, while the temporal separation was determined as the time-lag between the offset of the first flickering stimulus and the onset of the second. We found that the thresholds increased asymptotically with the spatial separation in such a way as to suggest that the spatial extent over which inhibitory interaction could be effective was as large as about 2 arc deg. We also found that the threshold gradually decreased with greater temporal separation; this indicated that the temporal proximity of successive stimuli effects less suppression on the temporal response. These two effects were seemingly additive. These findings suggest that the visual system involves not only local spatial interaction, but also a global mechanism capable of spreading inhibition over several local units after a delay of several msec.

Positional acuity with chromatic stimuli.

Theoretical reasons are presented for expecting a high precision spatial acuity task (vernier acuity) to be more difficult with an equiluminous stimulus than with stimuli containing luminance cues. This prediction was verified in Experiment 1. In a second experiment, it was shown that the result of the first experiment could not be explained by reduced detectability of the equiluminous target bar. We explain these results by the conflicting demands of chromatic and spatial differencing within a single mechanism, and propose that this also explains the similarities between long and medium wavelength cones in their spectral sensitivities.

Color-opponent characteristics revealed in temporal integration time.

The critical durations for temporal integration at threshold were obtained for lights of various wavelengths, presented both against darkness and against achromatic or chromatic backgrounds of different luminances. The critical duration (tc) was defined by a point of intersection of the two lines with the slopes of zero and unity in a log I.t-t plot, fitted by means of an algorithm implemented by computer program. tc was short for the lights of middle wavelengths, longer for the lights at the ends of the spectrum, and became shorter as the background luminance increased. tc also depended on the background wavelength, generally showing color-opponent characteristics when the difference was taken between tc's for the chromatic background and those for the achromatic one. The results were interpreted as the manifestation of chromatically-opponent system activities in temporal integration.

Temporal integration in human vision and the opponent-color systems.

The present study demonstrated that the temporal integration time (t.i.t.) could be prolonged even if the background energy was increased, provided that the background consisted of the colors opponent to each other. This was found, more or less, irrespective of the test stimulus size. These results suggest that the t.i.t. is not determined solely at receptor sites in the visual system, but that the chromatically-opponent systems are heavily involved. Mechanisms based upon a two-sites adaptation with one detection pathway model were briefly discussed.