Cupulolithiasis: A Critical Reappraisal.

Objective: To review the history and pathophysiologic theories for cupulolithiasis and canalith jam in benign paroxysmal positional vertigo. Data Sources: PubMed, Google Scholar. Review Methods: Three PubMed and Google Scholar searches were performed, keywords: "cupulolithiasis," "apogeotropic [and] benign," and "canalith jam," resulting in 187 unique full-text articles in English or with English translation. Figures-Labyrinthine photographs were obtained of fresh utricles, ampullae, and cupulae of a 37-day-old mouse. Conclusions: Freely moving otoconial masses explain most cases (>98%) of benign paroxysmal positional vertigo. Evidence that otoconia adhere strongly or persistently to the cupula is lacking. Apogeotropic nystagmus in the horizontal canal form is often attributed to cupulolithiasis; however, periampullary canalithiasis explains self-limited nystagmus, and reversible canalith jam explains prolonged apogeotropic nystagmus. Treatment-resistant cases can be explained by entrapment of particles in the canals or ampullae, but persistent adherence to the cupula remains theoretical. Implications for Practice: Apogeotropic nystagmus is usually due to freely moving particles and should not be used in studies of horizontal canal benign paroxysmal positional vertigo as the sole method to define entrapment or cupulolithiasis. Caloric testing and imaging may help differentiate jam from cupulolithiasis. Treatment for apogeotropic benign paroxysmal positional vertigo should include maneuvers that rotate the head through 270° to fully clear the canal of mobile particles, using mastoid vibration or head shaking if entrapment is suspected. Canal plugging can be used for treatment failures.

Consistent hearing aid use is associated with lower fall prevalence and risk in older adults with hearing loss.

BACKGROUND: Falls and their sequelae cost more than $50 billion every year. Older adults with hearing loss are at 2.4 times greater risk of falls than their normal hearing peers. Current research is inconclusive about whether hearing aids can offset this increased fall risk, and no previous studies considered if outcomes differed based on the consistency of hearing aid use. METHODS: Individuals 60 years and older with bilateral hearing loss completed a survey consisting of the Fall Risk Questionnaire (FRQ) and questions about hearing loss history, hearing aid use, and other common fall risk factors. In this cross-sectional study, fall prevalence, as well as fall risk (based on FRQ score), was compared between hearing aid users and non-users. A separate group of consistent hearing-aid users (at least 4 h daily use for more than 1 year) was also compared with inconsistent/non-users. RESULTS: Responses from 299 surveys were analyzed. Bivariate analysis found 50% reduced odds of experiencing a fall for hearing aid users compared with non-users (OR = 0.50 [95% CI: 0.29-0.85], p = 0.01). After adjusting for age, sex, hearing loss severity, and medication usage, those who reported any hearing aid use still had lower odds of falls (OR = 0.48 [95% CI: 0.26-0.90], p = 0.02) and lower odds of being at risk for falls (OR = 0.36 [95% CI: 0.19-0.66] p < 0.001) than non-users. Results for consistent hearing aid users demonstrate an even stronger association of lowered odds of falling (OR = 0.35 [95% CI: 0.19-0.67], p < 0.001) and lower odds of being at risk for falls (OR = 0.32 [95% CI: 0.12-0.59], p < 0.001), suggesting a potential dose-response relationship. CONCLUSIONS: These findings suggest that use of hearing aids-especially consistent hearing aid use-is associated with lower odds of experiencing a fall or being classified as at risk for falls in older individuals with hearing loss.

Adolescent and parent perceptions of patient-centered communication while managing type 1 diabetes.

OBJECTIVE: To examine whether adolescents' and parents' perceptions of patient-centered communication (PCC) with the physician may be associated with aspects of patient empowerment (e.g., perceptions of competence) and diabetes management (i.e., adherence and HbA1c). METHODS: One hundred and ninety adolescents with type 1 diabetes and their parents rated perceptions of PCC following a clinic visit and completed measures of competence, illness perceptions, self-efficacy, and adherence in the weeks following their clinic visit, and again 6 months later. Metabolic control was indexed from medical records. RESULTS: Higher levels of PCC with physicians were associated cross-sectionally and longitudinally with greater perceptions of control and competence for both adolescents and parents. Mediation analyses indicated that PCC was indirectly related to subsequent adherence and metabolic control through perceptions of the adolescent's competence in diabetes management. CONCLUSIONS: Perceptions of PCC with healthcare providers may empower adolescents and parents in their diabetes management.

Reversible Canalith Jam of the Horizontal Semicircular Canal Mimicking Cupulolithiasis.

OBJECTIVE: To describe a case of benign paroxysmal positional vertigo (BPPV) resulting in reversible horizontal semicircular canalith jam successfully treated with horizontal canal occlusion. A brief literature review of similar cases was performed. METHODS: Case report and literature review. RESULTS: A 68-year-old female presented with apogeotropic positional nystagmus, attributed to reversible horizontal canalith jam mimicking cupulolithiasis that was refractory to tailored repositioning maneuvers across months. She was unable to work due to the severity of her symptoms. She underwent surgical occlusion of the affected canal with immediate resolution of her symptoms. A literature review revealed similar cases of canalith jam mimicking cupulolithiasis. CONCLUSIONS: Reversible canalith jam, in which particles moving with horizontal head position alternate between obstructing the semicircular canal and resting on the cupula, can mimic signs of cupulolithiasis. This variant of BPPV can be effectively managed with surgical canal occlusion should symptoms fail to resolve after tailored repositioning maneuvers.

Identification of the novel protein QQS as a component of the starch metabolic network in Arabidopsis leaves.

Little is known about the role of proteins that lack primary sequence homology with any known motifs (proteins with unknown functions, PUFs); these comprise more than 10% of all proteins. This paper offers a generalized experimental strategy for identifying the functions of such proteins, particularly in relation to metabolism. Using this strategy, we have identified a novel regulatory function for Arabidopsis locus At3g30720 (which we term QQS for qua-quine starch). QQS expression, revealed through global mRNA profiling, is up-regulated in an Arabidopsis Atss3 mutant that lacks starch synthase III and has increased leaf starch content. Analysis of public microarray data using MetaOmGraph (metnetdb.org), in combination with transgenic Arabidopsis lines containing QQS promoter-GUS transgenes, indicated that QQS expression responds to a variety of developmental/genetic/environmental perturbations. In addition to the increase in the Atss3 mutant, QQS is up-regulated in the carbohydrate mutants mex1 and sis8. A 586 nt sequence for the QQS mRNA was identified by 5' and 3' RACE experiments. The QQS transcript is predicted to encode a protein of 59 amino acids, whose expression was confirmed by immunological Western blot analysis. The QQS gene is recognizable in sequenced Arabidopsis ecotypes, but is not identifiable in any other sequenced species, including the closely related Brassica napus. Transgenic RNA interference lines in which QQS expression is reduced show excess leaf starch content at the end of the illumination phase of a diurnal cycle. Taken together, the data identify QQS as a potential novel regulator of starch biosynthesis.

Parental involvement buffers associations between pump duration and metabolic control among adolescents with type 1 diabetes.

OBJECTIVES: To examine pump duration associations with adolescents' metabolic control and whether parental involvement moderated this association. METHODS: This study used a cross-sectional sample of 10- to 14-year-olds with diabetes (N = 252, 53.6% female) and parents' reported parental involvement; HbA1c was obtained from medical records. Half (50.8%) were on an insulin pump (continuous subcutaneous insulin infusion, CSII), with the remainder prescribed multiple daily injections (MDI). RESULTS: Adolescents on CSII displayed better HbA1c than those on MDI. A curvilinear association revealed that participants on CSII for <2 years showed a positive pump duration-HbA1c association, while those on CSII longer showed no association. Parental involvement interacted with pump duration to predict HbA1c. Pump duration was associated with poorer HbA1c only when parents were relatively uninvolved. CONCLUSIONS: Within the limitations of a cross-sectional design, data suggest that adolescents on CSII have better HbA1c than those on MDI, but may experience a period of deterioration that can be offset by parental involvement.

The Clinical Spectrum of Dizziness in Sleep Apnea.

OBJECTIVE: Sleep apnea has been associated with dizziness, but the clinical characteristics of this dizziness have not been fully described. This study evaluated clinical descriptions of dizziness, vestibular diagnoses, and the response to treatment of dizzy patients with sleep apnea. PATIENTS: All subjects had a new diagnosis of sleep apnea with a confirmatory pulse oximetry or polysomnogram and received treatment for sleep apnea through our center. Fifty-two patients met these criteria, with a mean age of 55 years and a mean BMI of 31. INTERVENTION: Continuous positive airway pressure or uvulopalatopharyngoplasty. MAIN OUTCOME MEASURES: Reported symptoms of dizziness and vestibular diagnoses were collected retrospectively in all patients. Nineteen patients with a complete resolution of dizziness with treatment of sleep apnea on mean follow-up of 4 years were used to define the clinical syndrome and their symptoms were compared with the remainder of the group. RESULTS: Repeated spells of sudden momentary vertigo were common. Vestibular migraine, Menière's disease, and sudden sensorineural hearing loss occurred in a much higher frequency than in the general population. CONCLUSIONS: Brief spells of nonpositional vertigo that recur throughout the day, phenotypically similar to vestibular paroxysmia, responded to treatment of sleep apnea, and could represent a new vestibular entity. The greatly elevated risk of migraine, Menière's disease and sudden sensorineural hearing loss are likely due to enhanced vascular risks associated with sleep apnea. A history of snoring should be sought in all dizzy patients.

Mothers', fathers', and children's perceptions of parental diabetes responsibility in adolescence: examining the roles of age, pubertal status, and efficacy.

OBJECTIVES: To examine how perceptions of parental responsibility for diabetes management are associated with age, pubertal status, adolescents' self-efficacy, and parental perceptions of adolescents' efficacy, and if parental responsibility is associated with better metabolic control as a function of adolescents' self-efficacy and parental perceptions of adolescents' efficacy. METHODS: Questionnaires assessing parental responsibility, pubertal status, adolescents' self-efficacy, and parental perceptions of adolescents' efficacy were given to 185 adolescents with type 1 diabetes, 185 mothers, and 145 fathers. RESULTS: Greater parental responsibility was negatively associated with age, perceptions of pubertal status, and efficacy for all reporters. Interactions between parental responsibility and parental perceptions of adolescents' efficacy indicated that parental responsibility was associated with better metabolic control when adolescents were perceived to have lower efficacy. CONCLUSIONS: Adolescents' and parents' perceptions of parental responsibility are related to multiple factors. Metabolic control is best when high parental responsibility is maintained among adolescents with lower efficacy.

Parental negative affect and adolescent efficacy for diabetes management.

The authors investigated whether parental perceptions of adolescent efficacy are colored by parental negative affect and are associated with adolescents' self-perceptions of efficacy for diabetes management. Adolescents (n = 183, M age = 12.53) with Type 1 diabetes and their mothers and fathers separately reported perceptions of adolescents' efficacy for diabetes management and parents reported their own negative affect (depressed mood and trait anxiety). glycosolated hemoglobin (HbA1c) levels were obtained from medical records. The results indicated that parental negative affect was associated with parental perceptions of poorer adolescent efficacy beyond the association of HbA1c scores. The relationship between fathers' negative affect and adolescents' self-efficacy was mediated by fathers' perceptions of adolescent efficacy. The results suggest that parental negative affect may negatively color their views of adolescents' efficacy and, in the case of fathers' beliefs, may relate to adolescent self-efficacy. Parental negative affect should be considered when evaluating perceptions of adolescents' efficacy.

The relationship between negative communication and body image dissatisfaction in adolescent females with Type 1 Diabetes Mellitus.

Maladaptive eating attitudes and behaviors are common in adolescent females with Type 1 Diabetes Mellitus (T1DM). This research assessed potential pathways through which individual and familial factors relate to treatment adherence and glycemic control. Seventy-five females with T1DM (aged 11-17 years) and their mothers completed questionnaires regarding communication, diabetes management, and eating attitudes and behaviors. Hierarchical regression analyses found that body image dissatisfaction moderates the relationship between negative communication and maladaptive eating attitudes and behaviors. Treatment adherence mediates the relationship between maladaptive eating attitudes and behaviors and glycemic control. None of the participants endorsed omitting insulin for the purposes of weight management. This study highlights the need to address familial and individual factors along with treatment adherence within this population.

Obesity and sex steroid changes across puberty: evidence for marked hyperandrogenemia in pre- and early pubertal obese girls.

CONTEXT: Peripubertal obesity is associated with abnormal sex steroid concentrations, but the timing of onset and degree of these abnormalities remain unclear. OBJECTIVE: The objective of the study was to assess the degree of hyperandrogenemia across puberty in obese girls and assess overnight sex steroid changes in Tanner stage 1-3 girls. DESIGN: This was a cross-sectional analysis. SETTING: The study was conducted at general clinical research centers. SUBJECTS: Thirty normal-weight (body mass index for age < 85%) and 74 obese (body mass index for age >or= 95%) peripubertal girls. INTERVENTION: Blood samples (circa 0500-0700 h) were taken while fasting. Samples from the preceding evening (circa 2300 h) were obtained in 23 Tanner 1-3 girls. MAIN OUTCOME MEASURES: Hormone concentrations stratified by Tanner stage were measured. RESULTS: Compared with normal-weight girls, mean free testosterone (T) was elevated 2- to 9-fold across puberty in obese girls, whereas fasting insulin was 3-fold elevated in obese Tanner 1-3 girls (P < 0.05). Mean LH was lower in obese Tanner 1 and 2 girls (P < 0.05) but not in more mature girls. In a subgroup of normal-weight Tanner 1-3 girls (n = 17), mean progesterone (P) and T increased overnight 2.3- and 2.4-fold, respectively (P

Relationships among body mass index, parental perceptions, birthweight and parental weight after referral to a weight clinic.

OBJECTIVE: We sought to determine whether, in a specialty referral clinic, parental perceptions of their child's obesity were commensurate with the child's body mass index z score. Secondarily, we examined the impact of birth weight and parental body mass index on their child's body mass index z score and review results of an intake questionnaire. DESIGN: Cross-sectional study SETTING: University of Michigan from March 21, 2003 through June 30, 2004 PARTICIPANTS: Eighty-two children ages 1-20.2 years of age INTERVENTION: Body mass index z score for all participants was calculated. An intake questionnaire was completed by caregivers in which they were asked to describe their child as little overweight, overweight, very overweight or obese. OUTCOME MEASURES: Mean body mass index z score was compared to each parental descriptor. Regression analysis related body mass index z score to birthweight and parental body mass index. RESULTS: Body mass index z score was not related to parental descriptors. Maternal body mass index and child birthweight were predictors of the child's body mass index z score (r2=0.15, p<0.05; and r2=0.11, p<0.05, respectively). Both together produced a better model than either alone (r2=0.23, p<0.05). There was no relationship between paternal and child body mass index z score (p>0.05). CONCLUSIONS: There is a divergence between the parental perception of childhood obesity and the clinical definition that persists even in the context of an explicit referral. Given the significant impact of maternal weight on childhood overweight, education for prevention of overweight youth should encompass prenatal, early childhood and adolescent health maintenance.

Intermediate care for older people.

Up to 40 per cent of older people do not go to hospital after calling an emergency ambulance and until recently were not referred on to any other community services. This article describes how a multidisciplinary working group developed and evaluated a protocol to enable older people to be referred to intermediate care services after calling an emergency ambulance. A total of 54 patients were monitored after referral to intermediate care to assess adherence to the protocol and outcomes.

The association of obesity and hyperandrogenemia during the pubertal transition in girls: obesity as a potential factor in the genesis of postpubertal hyperandrogenism.

CONTEXT: Adolescent hyperandrogenemia is considered a forerunner of adult polycystic ovary syndrome, but its etiology remains uncertain. OBJECTIVE: Our objective was to explore the hypothesis that peripubertal obesity is associated with hyperandrogenemia. DESIGN AND SETTING: We performed a cross-sectional analysis of data obtained at General Clinical Research Centers. SUBJECTS: Subjects were 41 obese [body mass index (BMI) for age, >or=95%] and 35 normal-weight (BMI for age, <95%) peripubertal girls. INTERVENTION: We used pooled blood samples (approximately 0500-0700 h; n = 64) while fasting or single morning (fasting) samples (n = 12). MAIN OUTCOME MEASURES: We assessed adiposity and androgen concentrations. RESULTS: BMI correlated with total testosterone (T) (r(s) = 0.59), SHBG (r(s) = -0.69), and free T (r(s) = 0.69); free T was three times as great in obese girls compared with normal-weight girls (P < 0.0001 for all). BMI correlated with insulin (r(s) = 0.52); both insulin and LH correlated with free T (r(s) = 0.45 and 0.44, respectively; P < 0.001 for all). When analyzing early pubertal girls (pubertal stages 1-3; n = 36) alone, BMI correlated with total T (r(s) = 0.65), SHBG (r(s) = -0.74), and free T (r(s) = 0.75); free T was five times as great in obese early-pubertal girls (P < 0.001 for all). BMI correlated with insulin (r(s) = 0.65), and insulin correlated with free T (r(s) = 0.63, P < 0.01 for both). BMI correlated with free T while simultaneously adjusting for age, pubertal stage, insulin, LH, and dehydroepiandrosterone sulfate. CONCLUSION: Peripubertal obesity is associated with marked hyperandrogenemia, which is especially pronounced in early puberty.

Meniere's disease.

Meniere's disease (MD) is a disorder of the inner ear that causes vertigo attacks, fluctuating hearing loss, tinnitus and aural fullness. The aetiology of MD is multifactorial. A characteristic sign of MD is endolymphatic hydrops (EH), a disorder in which excessive endolymph accumulates in the inner ear and causes damage to the ganglion cells. In most patients, the clinical symptoms of MD present after considerable accumulation of endolymph has occurred. However, some patients develop symptoms in the early stages of EH. The reason for the variability in the symptomatology is unknown and the relationship between EH and the clinical symptoms of MD requires further study. The diagnosis of MD is based on clinical symptoms but can be complemented with functional inner ear tests, including audiometry, vestibular-evoked myogenic potential testing, caloric testing, electrocochleography or head impulse tests. MRI has been optimized to directly visualize EH in the cochlea, vestibule and semicircular canals, and its use is shifting from the research setting to the clinic. The management of MD is mainly aimed at the relief of acute attacks of vertigo and the prevention of recurrent attacks. Therapeutic options are based on empirical evidence and include the management of risk factors and a conservative approach as the first line of treatment. When medical treatment is unable to suppress vertigo attacks, intratympanic gentamicin therapy or endolymphatic sac decompression surgery is usually considered. This Primer covers the pathophysiology, symptomatology, diagnosis, management, quality of life and prevention of MD.

Optimal management of Ménière's disease.

Confusion in the nomenclature of Ménière's disease and lack of a standard definition of the disorder until 1995 has hampered accurate assessment of treatment efficacy since the presently defined disorder was first described in 1938. The lack of a widely accepted mechanism of the disease has also delayed the development of rational treatments. Past treatments have focused on relieving elevated pressures in the hydropic ear and more recently on treatment of underlying migraine. Present dietary methods of control include sodium restriction and migraine trigger elimination. Pharmacologic treatments include diuretics, migraine prophylactic medications, histamine analogs, and oral steroids. Surgical procedures include intratympanic steroid perfusion, shunts, and ablative procedures when conservative treatments fail. External pressure devices are also used. Evidence of efficacy is lacking for most interventions other than ablation. At our institution, Ménière's disease is treated as a cerebrovascular disorder. Control of risk factors for cerebrovascular ischemia is combined with treatment of pressure dysfunction in the hydropic ear. Screening for risk factors is performed at presentation. Migraine, dyslipidemia, obesity, diabetes, sleep apnea, hypertension, and atherosclerosis are among the major factors that often require medical management. Migraine prophylactic medications, magnesium supplementation, sodium restriction, migraine trigger elimination, diuretics, anticoagulants, and antihypertensives are among the treatments used initially. Steroids administered orally or intratympanically are used if control is not achieved medically, and ablation remains the definitive treatment in unilateral cases experiencing treatment failure.

Incomplete modified fast in obese early pubertal girls leads to an increase in 24-hour growth hormone concentration and a lessening of the circadian pattern in leptin.

We studied nutrition and GH in eight obese girls, aged 6-11 yr. Blood was sampled every 15 min for 24 h. A 48-h diet providing 25% of assumed caloric needs was imposed, with repeat sampling during the last 24 h. Six nonfasting lean girls were also studied, and their mean GH was 3 times that of the obese girls in the fed state (P = 0.024). Dieting increased mean GH by 60% (P = 0.0028). There was no difference in pulse number for either group, but total secretion for lean girls was 3.9 times greater than that in obese girls during the fed state. With dieting, obese girls increased their total GH secretion by 60% (P = 0.010), but maintained lower total secretion, approximately 40% that of lean girls (P = 0.014). Mean leptin in obese girls in the fed state was 6.2 times greater than mean leptin in lean girls (P = 0.0001), with higher concentrations at night (P < 0.05) and lowering of total mean leptin while dieting. We conclude that in early pubertal obese girls, short-term caloric restriction partially reverses the low GH state that is characteristic of obesity. The change is concomitant with a decrease in leptin and a lessening of circadian differences.

Augmentation of growth hormone secretion after testosterone treatment in boys with constitutional delay of growth and adolescence: evidence against an increase in hypothalamic secretion of growth hormone-releasing hormone.

The increase in pituitary GH secretion that occurs during mid-late puberty in boys follows an increase in circulating testosterone (T) concentration; the direct mechanism by which this occurs is unknown. We hypothesized that T increases GH secretion during puberty by augmenting hypothalamic output of GHRH. Using constant infusions of a GHRH antagonist, we tested this hypothesis in six early pubertal boys with constitutional delay of growth and adolescence who had a mean chronological age of 14.0 +/- 0.3 yr and mean bone age of 11.4 +/- 0.2 yr. Blood samples were obtained from subjects every 15 min for 24 h during the overnight infusion of normal saline (2000-0600 h) and again during the overnight infusion of GHRH antagonist (0.33 microg/kg/h) the following night. Subjects then received transdermal T (5-mg patch) for 12 h nightly and were studied again after 4 wk of treatment. Serum samples were assayed for GH and total ghrelin; the percent suppression of GH during GHRH antagonist infusion was calculated. Morning serum T rose from 0.44 +/- 0.09 to 4.43 +/- 0.74 microg/liter (P = 0.005). T treatment was associated with a 92.6% increase in mean nocturnal GH secretion area under the curve (830 +/- 177 to 1599 +/- 340 microg/24 h.liter). Infusion of GHRH-antagonist suppressed mean nocturnal GH area under the curve by 29.1% before T treatment (830 +/- 177 to 621 +/- 168 microg/24 h.liter), and by 29.4% after T treatment (1599 +/- 340 to 1182 +/- 249 microg/24 h.liter; P = 0.99). Somatotroph sensitivity to GHRH was tested with 0.1- and 1.0-microg/kg doses of GHRH-44 iv; GH response did not change with regard to T treatment. The mean 24-h concentration of total ghrelin was unchanged with regard to T treatment. In summary, nightly transdermal T administration in six boys with constitutional delay of growth and adolescence increased GH output almost 2-fold, whereas the degree of GH suppressibility by GHRH antagonist remained unchanged. We conclude that the T-associated augmentation of GH secretion during early puberty in boys is unlikely to involve an absolute increase in hypothalamic GHRH output.

Endolymphatic hydrops in Ménière's disease: cause, consequence, or epiphenomenon?

OBJECTIVE: To determine the relationship of endolymphatic hydrops to Ménière's disease. DATA SOURCES: Comprehensive review of articles from 1938 through 2012 via Medline and Index Medicus. STUDY SELECTION: Articles discussing Ménière's disease and/or endolymphatic hydrops that include temporal bone autopsy data. DATA EXTRACTION: Fifty-three case reports and series were studied containing examination of 541 hydropic temporal bones and including 276 patients with Ménière's disease. These were divided into those meeting the 1995 American Academy of Otolaryngology-Head and Neck Surgery criteria for Ménière's disease and those that failed to meet these criteria. CONCLUSION: An individual meeting the 1995 criteria for Ménière's disease has a near certain probability of having endolymphatic hydrops in at least 1 ear. Autopsy data do not support the view that the association of MD and EH is an epiphenomenon or that MD causes EH; this leaves us with the probability that EH causes MD. If it is causative, hydrops alone is insufficient to cause Ménière's disease, indicating that there must be one or more additional cofactors that cause asymptomatic hydrops to become symptomatic Ménière's disease. Vascular risk factors should be studied as possible cofactors.