Yael Raz | The Hebrew University of Jerusalem (original) (raw)

Papers by Yael Raz

Otolaryngology Head and Neck Surgery, 2011

PROGRAM DESCRIPTION: Hoarseness is an exceptionally common symptom that often will lead to a refe... more PROGRAM DESCRIPTION: Hoarseness is an exceptionally common symptom that often will lead to a referral to an otolaryngologist. Although frequently self-limited, hoarseness can persist and lead to significant dysfunction as well as portend potentially life threatening illness. The otolaryngologist plays a unique role on the appropriate diagnosis and treatment of hoarseness, while considering the health care costs of care. Fortunately the directed history and physical examination will often yield the diagnosis, but this is not always the case. The role of more complex evaluation modalities such as laryngeal videostroboscopy and electromyography are not as straight forward. Even more complex is the treatment, such as for laryngopharyngeal reflux, or the timing of surgery in relationship to speech therapy. This subject has been the focus of much recent interest, and by having input in an open panel format, the practitioner will be offered guidelines to modern management based on the recent literature. Focused history and physical examination will be reviewed as well on the components of a thorough physical examination. The place of more sophisticated diagnostic modalities will be discussed as well as various treatment options whether they be medical, voice therapy, or surgical. Case examples will form the basis for discussion, with ample time for audience interaction. EDUCATIONAL OBJECTIVES: 1) Understand the elements of a history and physical examination of an adult patient with hoarseness. 2) Discern the appropriate role of ancillary diagnostic studies such as videostroboscopy and electromyography. 3) Comprehend, based on current information, treatment modalities such a medications, voice therapy, and surgery.

American journal of obstetrics and gynecology, Jan 8, 2015

EuroIntervention, 2008

There are limited data regarding clinical outcomes of drug-eluting stents (DES) in saphenous vein... more There are limited data regarding clinical outcomes of drug-eluting stents (DES) in saphenous vein grafts (SVGs) compared to bare metal stents (BMS). Here we compared outcomes of DES in de novo SVG lesions versus BMS in contemporary percutaneous coronary intervention (PCI). We compared in-hospital, 6-month, 1-year and two years outcomes in 68 patients (72 grafts) who underwent PCI of SVG lesions using DES and a control BMS group composed of 43 patients (46 grafts) who underwent angioplasty in de novo SVG lesions. Major adverse cardiac events (MACE) included death, myocardial infarction (MI), target lesion revascularisation (TLR), and target vessel revascularisation (TVR). The rates of TLR and TVR at the 1-year evaluation were lower in the DES group than the BMS group (TLR per patient, 7.4% vs. 21%, P=0.04; TVR per patient, 10.3% vs. 23.3%, P=0.1). MACE-free survival was 88.2% in the DES group and 69.8% in the BMS group (P=0.02). At two years clinical follow-up: death 2.9% vs. 4.7% (P=0.6); MI: 8.8% vs. 7% (P=0.6). The rates of TLR and TVR were significantly lower in the DES group compared to the BMS group (TLR per patient, 14.7% vs. 32.6%, P=0.03; TVR per patient, 10.3% vs. 27.9%, P=0.02). The rate of MACE-free survival was 79.4% in the DES group and 58.1% in the BMS group (P=0.02). Between one to two years after PCI, no cases of angiographic stent thrombosis were recorded in either group. DES implantation in SVG lesions was safe and had favourable outcomes after two years without excess cardiac mortality.

Hormones and Behavior, 2015

Empathy is the ability to recognize and share in the emotions of others. It can be considered a m... more Empathy is the ability to recognize and share in the emotions of others. It can be considered a multifaceted concept with cognitive and emotional aspects. Little is known regarding the underlying neurochemistry of empathy and in the current study we used a neurogenetic approach to explore possible brain neurotransmitter pathways contributing to cognitive and emotional empathy. Both the oxytocin receptor (OXTR) and the arginine vasopressin receptor 1a (AVPR1a) genes contribute to social cognition in both animals and humans and hence are prominent candidates for contributing to empathy. The following research examined the associations between polymorphisms in these two genes and individual differences in emotional and cognitive empathy in a sample of 367 young adults. Intriguingly, we found that emotional empathy was associated solely with OXTR, whereas cognitive empathy was associated solely with AVPR1a. Moreover, no interaction was observed between the two genes and measures of empathy. The current findings contribute to our understanding of the distinct neurogenetic pathways involved in cognitive and emotional empathy and underscore the pervasive role of both oxytocin and vasopressin in modulating human emotions.

Otology & Neurotology, 2014

To assess intracranial pressure (ICP), body mass index (BMI), surgical repair, and cerebrospinal ... more To assess intracranial pressure (ICP), body mass index (BMI), surgical repair, and cerebrospinal fluid (CSF) diversion in patients presenting with spontaneous CSF otorrhea. Retrospective series review. Tertiary referral center. Thirty-two patients were treated surgically from 2004 to 2013 for spontaneous CSF otorrhea by the principal investigators. Patients with a history of chronic ear disease and cholesteatoma, previous mastoid surgery, head trauma, or iatrogenic injury were excluded. Average age was 56 years. Twenty-two patients (69%) were female. Middle fossa repair, transmastoid repair, lumbar puncture, V-P shunt, L-P shunt, and magnetic resonance imaging. Patients underwent middle fossa or transmastoid repair of tegmen defects. Intracranial pressures were determined with lumbar puncture at time of surgical repair or shortly after surgery. CSF diversion procedures were performed in patients who were found to have elevated ICP, which was not controlled medically, presented with recurrent leak or had ICP of 25 cm or greater of H2O. Preoperative BMI was calculated. Thirty-two patients underwent 37 operations. Average BMI was 35.0 kg/m2 (median, 34.7; range, 18.7-53.2 kg/m2). There were 21 repairs on the left and 16 on the right. The majority underwent a middle fossa craniotomy for repair (27/32). Two patients had bilateral repairs. Three patients (8%) underwent revision surgery, of which, 2 had untreated intracranial hypertension (ICP 24.5 and 24 cm H2O). ICP measurements were available for 29 patients. The mean ICP was 23.4 cm H2O (median, 24; range, 13-36 cm H20). Twenty-two patients (69%) had ICP of 20 cm or greater of H20; of those, 13 had an ICP of 25 cm or greater of H20. Seventeen patients (53%) underwent CSF diversion procedures. Our findings of elevated ICP and BMI in patients presenting with spontaneous CSF otorrhea are consistent with previous reports in the literature. The percentage of patients that underwent CSF diversion procedures was high at 53% and represents an aggressive stance in managing elevated ICP in a population that may be at risk for subsequent leaks.

Emotion, 2014

Increasing evidence points to a role of dopaminergic pathways in modulating social behavior. Spec... more Increasing evidence points to a role of dopaminergic pathways in modulating social behavior. Specifically, a polymorphic region in the third exon of the Dopamine D4 receptor (DRD4) has been associated with a host of social behaviors, often in an environment-sensitive manner. Empathy is thought to be an important motivator of prosocial behaviors and can be seen as multifaceted, combining cognitive empathy (CE) and emotional empathy (EE). In the current study, we analyzed the association between DRD4 and the 2 aspects of empathy, as well as the effect of gender on this association. In Study 1, a large sample of adult participants (N = 477) was inventoried for general empathy, CE, and EE and genotyped for the DRD4 exon 3 polymorphism. Women scored higher than men on all empathy measures and no main effect of genotype was observed. It is important that a significant interaction between genotype and gender emerged specifically for CE, with women carriers of the 7R-allele scoring higher than noncarriers, whereas in men 7R-carriers scored lower than -7R. Notably, these findings were replicated in an independently recruited sample (N = 121) in Study 2. The current report shows that the DRD4 exon3 polymorphism is associated with CE and the direction of the association is gender-sensitive.

Otolaryngology - Head and Neck Surgery, 2010

PROGRAM DESCRIPTION: Hoarseness is an exceptionally common symptom that often will lead to a refe... more PROGRAM DESCRIPTION: Hoarseness is an exceptionally common symptom that often will lead to a referral to an otolaryngologist. Although frequently self-limited, hoarseness can persist and lead to significant dysfunction as well as portend potentially life threatening illness. The otolaryngologist plays a unique role on the appropriate diagnosis and treatment of hoarseness, while considering the health care costs of care. Fortunately the directed history and physical examination will often yield the diagnosis, but this is not always the case. The role of more complex evaluation modalities such as laryngeal videostroboscopy and electromyography are not as straight forward. Even more complex is the treatment, such as for laryngopharyngeal reflux, or the timing of surgery in relationship to speech therapy. This subject has been the focus of much recent interest, and by having input in an open panel format, the practitioner will be offered guidelines to modern management based on the recent literature. Focused history and physical examination will be reviewed as well on the components of a thorough physical examination. The place of more sophisticated diagnostic modalities will be discussed as well as various treatment options whether they be medical, voice therapy, or surgical. Case examples will form the basis for discussion, with ample time for audience interaction. EDUCATIONAL OBJECTIVES: 1) Understand the elements of a history and physical examination of an adult patient with hoarseness. 2) Discern the appropriate role of ancillary diagnostic studies such as videostroboscopy and electromyography. 3) Comprehend, based on current information, treatment modalities such a medications, voice therapy, and surgery.

Otolaryngologic Clinics of North America, 2002

Congenital middle ear anomalies pose a challenge to clinicians because they present in a myriad o... more Congenital middle ear anomalies pose a challenge to clinicians because they present in a myriad of ways; however, advances in the diagnosis and treatment of these relatively uncommon ear disorders over the past decade have simplified the care of patients who suffer from them. This article focuses on the evaluation of congenital middle ear anomalies (excluding congenital cholesteatoma and aural atresia) as well as their surgical management.

Developmental Neuroscience, 1991

We have reexamined the levels of myelin basic protein (MBP) and proteolipid protein (PLP) in the ... more We have reexamined the levels of myelin basic protein (MBP) and proteolipid protein (PLP) in the brains of mice bred to carry both the shi/shi and jp/Y hypomyelination defects. The genotype of each putative double mutant was confirmed by direct DNA analysis: shi/shi by Southern blot analysis, and jp/Y by restriction enzyme analysis of polymerase chain reaction-amplified fragments. MBP and PLP levels were assessed by immunoblotting. All putative double mutants were found to be shi/shi. However, examination of the PLP locus revealed both jp and wild-type genotypes, the latter produced by an expected crossover. Animals proven to be shi/shi*jp/Y hadno detectable MBP or PLP; those proven to be shi/shi*+/Y (the crossover) had no MBP but had PLP. These results differ from an earlier report of both MBP and PLP in the brains of presumed shi*jp animals.Copyright © 1991 S. Karger AG, Basel

American Journal of Obstetrics and Gynecology, 2012

A copious watery vaginal discharge was the symptom in 2 similar, although unusual cases. The firs... more A copious watery vaginal discharge was the symptom in 2 similar, although unusual cases. The first patient, a 51-year-old woman, also reported that the discharge was bloody. Twelve years earlier, she had undergone surgery and chemoradiation therapy for cervical cancer. Three years later, she had laser ablation for vaginal intraepithelial neoplasia grade 2. She was then lost to follow-up evaluation until 6 months before her current admission, when she sought treatment for the vaginal exudate. A biopsy identified colonies of Actinomyces species, and she was treated with penicillin. When her symptoms persisted, a second biopsy was performed that revealed squamous cell carcinoma. After a metastatic work-up, she underwent total pelvic exenteration.

American Journal of Obstetrics and Gynecology, 2015

Intrahepatic cholestasis of pregnancy (ICP) is known to be associated with fetal complications. I... more Intrahepatic cholestasis of pregnancy (ICP) is known to be associated with fetal complications. It recently was suggested to be associated possibly with preeclampsia (PET) as well. The objective of this study was to investigate that possibility. The study group included 78 women (54 singleton and 24 twin pregnancies) who had been diagnosed with ICP based on clinical presentation, elevated liver enzymes, and elevated total bile acids (>10 μmol/L). Disease severity was based on total bile acids levels as being severe (>40 μmol/L), moderate (20-40 μmol/L), or mild (10-20 μmol/L). The course of disease was reviewed carefully in each case. The control groups were comprised of apparently healthy women with singleton (n = 200) and twin (n = 100) pregnancies that were drawn randomly from a computerized registry of all the deliveries in our institution during the study period. The total incidence of PET was significantly higher for the patients with ICP who had singleton and twin pregnancies compared with the control groups (singletons: 7.4% vs 1.5%; P < .05; twins: 33.3% vs 6.2%; P < .05, respectively). The incidence of severe PET was also significantly higher in both singleton (11-fold) and twin (8-fold) pregnancies compared with control subjects. Severe ICP, but not mild ICP, was a major risk factor for PET among women with either singleton or twin pregnancies. The timing of the initial presentation of ICP had no effect on PET incidence rates. Preeclampsia occurred usually 2-4 weeks after the diagnosis of ICP, and proteinuria preceded elevated blood pressure in all cases. Moreover, the total bile acid levels among 33 women who were diagnosed as having PET, but not ICP, were within normal range. ICP increases the incidence of PET; severe disease was a major risk factor for preeclampsia. Therefore, we strongly suggest including routine evaluation for preeclampsia in the treatment of women with moderate and severe ICP.

Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 2014

Current Opinion in Otolaryngology & Head and Neck Surgery, 2010

This review discusses the demographics of dizziness in the older person, the evaluation of the ol... more This review discusses the demographics of dizziness in the older person, the evaluation of the older dizzy patient and how the treatment of dizziness in older patients differs from that in younger individuals. Seven percent of all visits to primary care physicians for patients older than 65 years of age are for dizziness, and dizziness is the most common complaint for patients older than 75 years. In a German study, the 12-month prevalence of vertigo in the general population was 5% with an incidence of 1.4% in adults overall. For individuals aged 60-69 the 12-month prevalence was found to be 7.2% and in individuals 70 years of age or older 8.9%. Data from the United States National Health and Nutrition Examination Surveys indicated that the prevalence of vestibular dysfunction for individuals in the seventh decade of life, eighth decade of life, and older was 49.4, 68.7, and 84.8 percent, respectively. Only subtle age effects are seen on caloric and rotational testing whereas vestibular evoked myogenic potentials (VEMPs) change somewhat with age. Particle repositioning for benign paroxysmal positional vertigo combined with vestibular rehabilitation is more effective than only performing the repositioning maneuver. Tai Chi appears to be an effective intervention for older adults at risk for falling. When caring for an older dizzy patient always assess medication use, perform a Dix-Hallpike maneuver, obtain orthostatic vital signs, discuss fall risk precautions, and consider referral for vestibular rehabilitation.

Cancer Research, 2015

Breast tumors are characterized by an extensive desmoplastic stroma, abundantly populated by fibr... more Breast tumors are characterized by an extensive desmoplastic stroma, abundantly populated by fibroblasts. Cancer-associated fibroblasts (CAF) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and invasion. CAF also orchestrate tumor-promoting inflammation in multiple tumor types, including breast cancer. However, the mechanisms through which normal tissue fibroblasts are reprogrammed to tumor-promoting CAFs are mainly obscure. Here, we show that mammary fibroblasts can be educated by breast cancer cells to become activated to a proinflammatory state that supports malignant progression. Proteomic analysis of breast cancer cell-secreted factors identified the secreted proinflammatory mediator osteopontin, which has been implicated in inflammation, tumor progression, and metas-tasis. Osteopontin was highly secreted by mouse and human breast cancer cells, and tumor cell-secreted osteopontin activated a CAF phenotypes in normal mammary fibroblasts in vitro and in vivo. Osteopontin was sufficient to induce fibroblast reprogramming and neutralizing antibodies against osteopontinblocked fibroblast activation induced by tumor cells. The ability of secreted osteopontin to activate mammary fibroblasts relied upon its known receptors CD44 and a V b 3 integrin. Strikingly, osteopontin silencing in tumor cells in vivo attenuated stromal activation and inhibited tumor growth. Our findings establish a critical functional role for paracrine signaling by tumor-derived osteopontin in reprograming normal fibroblasts into tumor-promoting CAFs. Cancer Res; 75(6); 963-73. Ó2015 AACR.

Seminars in Cell & Developmental Biology, 1997

The sensory epithelia of the vertebrate inner ear are comprised of a complex pattern of hair cell... more The sensory epithelia of the vertebrate inner ear are comprised of a complex pattern of hair cells and supporting cells. Several different families of signaling molecules have been shown to play a role in the development and maintenance of this structure. In particular, the steroid/thyroid receptor superfamily, and specifically retinoid and thyroid receptors appear to influence the determination, differentiation, maintenance, and possibly regeneration, of the sensory epithelia of the vertebrate inner ear. Clinical and experimental evidence demonstrates that changes in the relative availability of retinoic acid and thyroid hormone, the ligands for retinoid and thyroid receptors, result in perturbations in the development of hair cell sensory epithelia. Retinoic acid and retinoid receptors appear to play a role in early developmental events including cellular proliferation and determination whereas thyroid hormone and thyroid receptors appear to play a role in later events including differentiation and maintenance.

Psychiatric Genetics, 2010

This study examined the influence of allelic variation in two dopamine genes, the dopamine recept... more This study examined the influence of allelic variation in two dopamine genes, the dopamine receptor D4 (DRD4) gene and the dopamine transporter D1 (DAT1) gene, and paternal attention-deficit hyperactivity disorder (ADHD) symptomatology on the level of ADHD symptoms in 96 four and a half-year-old boys. DNA was collected by means of a buccal swab and genotyped for DRD4 and DAT1. Mothers completed the Dupaul ADHD checklist on their sons. ADHD symptomatology ratings for fathers were based on a summed father self-reported and spouse-reported symptoms (Conners Adult ADHD Rating Scale). There were main effects for DAT1 and father symptomatology for the child Total ADHD and Hyperactivity-Impulsivity scores. The main effects for DRD4 were limited to the child Hyperactivity-Impulsivity scores. Child Inattentive scores were influenced only by father symptomatology. Interaction effects between DAT1 and DRD4 and between DAT1 and the father ADHD risk group were found for child Hyperactivity-Impulsivity scores. Boys with the highest level of symptomatology were those with the 10/10 DAT1 genotype and the DRD4-7 genotype or fathers with high symptomatology. The findings of this study indicate that the risk for ADHD, particularly hyperactivity-impulsivity, is exacerbated in the presence of dopamine risk genes and paternal ADHD symptomatology. This study adds to the growing literature on the efficacy of including multiple genetic and environmental risk factors in studies related to the development of psychopathology.

Otolaryngology -- Head and Neck Surgery, 2013

Objective: 1) To evaluate a novel system for regulating the chitosan-glycero-phosphate (CGP)-base... more Objective: 1) To evaluate a novel system for regulating the chitosan-glycero-phosphate (CGP)-based hydrogel drug delivery to the inner ear. 2) To understand the distribution of gentamicin in the inner ear following CGP drug delivery with and without regulation.

Otolaryngology Head and Neck Surgery, 2011

PROGRAM DESCRIPTION: Hoarseness is an exceptionally common symptom that often will lead to a refe... more PROGRAM DESCRIPTION: Hoarseness is an exceptionally common symptom that often will lead to a referral to an otolaryngologist. Although frequently self-limited, hoarseness can persist and lead to significant dysfunction as well as portend potentially life threatening illness. The otolaryngologist plays a unique role on the appropriate diagnosis and treatment of hoarseness, while considering the health care costs of care. Fortunately the directed history and physical examination will often yield the diagnosis, but this is not always the case. The role of more complex evaluation modalities such as laryngeal videostroboscopy and electromyography are not as straight forward. Even more complex is the treatment, such as for laryngopharyngeal reflux, or the timing of surgery in relationship to speech therapy. This subject has been the focus of much recent interest, and by having input in an open panel format, the practitioner will be offered guidelines to modern management based on the recent literature. Focused history and physical examination will be reviewed as well on the components of a thorough physical examination. The place of more sophisticated diagnostic modalities will be discussed as well as various treatment options whether they be medical, voice therapy, or surgical. Case examples will form the basis for discussion, with ample time for audience interaction. EDUCATIONAL OBJECTIVES: 1) Understand the elements of a history and physical examination of an adult patient with hoarseness. 2) Discern the appropriate role of ancillary diagnostic studies such as videostroboscopy and electromyography. 3) Comprehend, based on current information, treatment modalities such a medications, voice therapy, and surgery.

American journal of obstetrics and gynecology, Jan 8, 2015

EuroIntervention, 2008

There are limited data regarding clinical outcomes of drug-eluting stents (DES) in saphenous vein... more There are limited data regarding clinical outcomes of drug-eluting stents (DES) in saphenous vein grafts (SVGs) compared to bare metal stents (BMS). Here we compared outcomes of DES in de novo SVG lesions versus BMS in contemporary percutaneous coronary intervention (PCI). We compared in-hospital, 6-month, 1-year and two years outcomes in 68 patients (72 grafts) who underwent PCI of SVG lesions using DES and a control BMS group composed of 43 patients (46 grafts) who underwent angioplasty in de novo SVG lesions. Major adverse cardiac events (MACE) included death, myocardial infarction (MI), target lesion revascularisation (TLR), and target vessel revascularisation (TVR). The rates of TLR and TVR at the 1-year evaluation were lower in the DES group than the BMS group (TLR per patient, 7.4% vs. 21%, P=0.04; TVR per patient, 10.3% vs. 23.3%, P=0.1). MACE-free survival was 88.2% in the DES group and 69.8% in the BMS group (P=0.02). At two years clinical follow-up: death 2.9% vs. 4.7% (P=0.6); MI: 8.8% vs. 7% (P=0.6). The rates of TLR and TVR were significantly lower in the DES group compared to the BMS group (TLR per patient, 14.7% vs. 32.6%, P=0.03; TVR per patient, 10.3% vs. 27.9%, P=0.02). The rate of MACE-free survival was 79.4% in the DES group and 58.1% in the BMS group (P=0.02). Between one to two years after PCI, no cases of angiographic stent thrombosis were recorded in either group. DES implantation in SVG lesions was safe and had favourable outcomes after two years without excess cardiac mortality.

Hormones and Behavior, 2015

Empathy is the ability to recognize and share in the emotions of others. It can be considered a m... more Empathy is the ability to recognize and share in the emotions of others. It can be considered a multifaceted concept with cognitive and emotional aspects. Little is known regarding the underlying neurochemistry of empathy and in the current study we used a neurogenetic approach to explore possible brain neurotransmitter pathways contributing to cognitive and emotional empathy. Both the oxytocin receptor (OXTR) and the arginine vasopressin receptor 1a (AVPR1a) genes contribute to social cognition in both animals and humans and hence are prominent candidates for contributing to empathy. The following research examined the associations between polymorphisms in these two genes and individual differences in emotional and cognitive empathy in a sample of 367 young adults. Intriguingly, we found that emotional empathy was associated solely with OXTR, whereas cognitive empathy was associated solely with AVPR1a. Moreover, no interaction was observed between the two genes and measures of empathy. The current findings contribute to our understanding of the distinct neurogenetic pathways involved in cognitive and emotional empathy and underscore the pervasive role of both oxytocin and vasopressin in modulating human emotions.

Otology & Neurotology, 2014

To assess intracranial pressure (ICP), body mass index (BMI), surgical repair, and cerebrospinal ... more To assess intracranial pressure (ICP), body mass index (BMI), surgical repair, and cerebrospinal fluid (CSF) diversion in patients presenting with spontaneous CSF otorrhea. Retrospective series review. Tertiary referral center. Thirty-two patients were treated surgically from 2004 to 2013 for spontaneous CSF otorrhea by the principal investigators. Patients with a history of chronic ear disease and cholesteatoma, previous mastoid surgery, head trauma, or iatrogenic injury were excluded. Average age was 56 years. Twenty-two patients (69%) were female. Middle fossa repair, transmastoid repair, lumbar puncture, V-P shunt, L-P shunt, and magnetic resonance imaging. Patients underwent middle fossa or transmastoid repair of tegmen defects. Intracranial pressures were determined with lumbar puncture at time of surgical repair or shortly after surgery. CSF diversion procedures were performed in patients who were found to have elevated ICP, which was not controlled medically, presented with recurrent leak or had ICP of 25 cm or greater of H2O. Preoperative BMI was calculated. Thirty-two patients underwent 37 operations. Average BMI was 35.0 kg/m2 (median, 34.7; range, 18.7-53.2 kg/m2). There were 21 repairs on the left and 16 on the right. The majority underwent a middle fossa craniotomy for repair (27/32). Two patients had bilateral repairs. Three patients (8%) underwent revision surgery, of which, 2 had untreated intracranial hypertension (ICP 24.5 and 24 cm H2O). ICP measurements were available for 29 patients. The mean ICP was 23.4 cm H2O (median, 24; range, 13-36 cm H20). Twenty-two patients (69%) had ICP of 20 cm or greater of H20; of those, 13 had an ICP of 25 cm or greater of H20. Seventeen patients (53%) underwent CSF diversion procedures. Our findings of elevated ICP and BMI in patients presenting with spontaneous CSF otorrhea are consistent with previous reports in the literature. The percentage of patients that underwent CSF diversion procedures was high at 53% and represents an aggressive stance in managing elevated ICP in a population that may be at risk for subsequent leaks.

Emotion, 2014

Increasing evidence points to a role of dopaminergic pathways in modulating social behavior. Spec... more Increasing evidence points to a role of dopaminergic pathways in modulating social behavior. Specifically, a polymorphic region in the third exon of the Dopamine D4 receptor (DRD4) has been associated with a host of social behaviors, often in an environment-sensitive manner. Empathy is thought to be an important motivator of prosocial behaviors and can be seen as multifaceted, combining cognitive empathy (CE) and emotional empathy (EE). In the current study, we analyzed the association between DRD4 and the 2 aspects of empathy, as well as the effect of gender on this association. In Study 1, a large sample of adult participants (N = 477) was inventoried for general empathy, CE, and EE and genotyped for the DRD4 exon 3 polymorphism. Women scored higher than men on all empathy measures and no main effect of genotype was observed. It is important that a significant interaction between genotype and gender emerged specifically for CE, with women carriers of the 7R-allele scoring higher than noncarriers, whereas in men 7R-carriers scored lower than -7R. Notably, these findings were replicated in an independently recruited sample (N = 121) in Study 2. The current report shows that the DRD4 exon3 polymorphism is associated with CE and the direction of the association is gender-sensitive.

Otolaryngology - Head and Neck Surgery, 2010

PROGRAM DESCRIPTION: Hoarseness is an exceptionally common symptom that often will lead to a refe... more PROGRAM DESCRIPTION: Hoarseness is an exceptionally common symptom that often will lead to a referral to an otolaryngologist. Although frequently self-limited, hoarseness can persist and lead to significant dysfunction as well as portend potentially life threatening illness. The otolaryngologist plays a unique role on the appropriate diagnosis and treatment of hoarseness, while considering the health care costs of care. Fortunately the directed history and physical examination will often yield the diagnosis, but this is not always the case. The role of more complex evaluation modalities such as laryngeal videostroboscopy and electromyography are not as straight forward. Even more complex is the treatment, such as for laryngopharyngeal reflux, or the timing of surgery in relationship to speech therapy. This subject has been the focus of much recent interest, and by having input in an open panel format, the practitioner will be offered guidelines to modern management based on the recent literature. Focused history and physical examination will be reviewed as well on the components of a thorough physical examination. The place of more sophisticated diagnostic modalities will be discussed as well as various treatment options whether they be medical, voice therapy, or surgical. Case examples will form the basis for discussion, with ample time for audience interaction. EDUCATIONAL OBJECTIVES: 1) Understand the elements of a history and physical examination of an adult patient with hoarseness. 2) Discern the appropriate role of ancillary diagnostic studies such as videostroboscopy and electromyography. 3) Comprehend, based on current information, treatment modalities such a medications, voice therapy, and surgery.

Otolaryngologic Clinics of North America, 2002

Congenital middle ear anomalies pose a challenge to clinicians because they present in a myriad o... more Congenital middle ear anomalies pose a challenge to clinicians because they present in a myriad of ways; however, advances in the diagnosis and treatment of these relatively uncommon ear disorders over the past decade have simplified the care of patients who suffer from them. This article focuses on the evaluation of congenital middle ear anomalies (excluding congenital cholesteatoma and aural atresia) as well as their surgical management.

Developmental Neuroscience, 1991

We have reexamined the levels of myelin basic protein (MBP) and proteolipid protein (PLP) in the ... more We have reexamined the levels of myelin basic protein (MBP) and proteolipid protein (PLP) in the brains of mice bred to carry both the shi/shi and jp/Y hypomyelination defects. The genotype of each putative double mutant was confirmed by direct DNA analysis: shi/shi by Southern blot analysis, and jp/Y by restriction enzyme analysis of polymerase chain reaction-amplified fragments. MBP and PLP levels were assessed by immunoblotting. All putative double mutants were found to be shi/shi. However, examination of the PLP locus revealed both jp and wild-type genotypes, the latter produced by an expected crossover. Animals proven to be shi/shi*jp/Y hadno detectable MBP or PLP; those proven to be shi/shi*+/Y (the crossover) had no MBP but had PLP. These results differ from an earlier report of both MBP and PLP in the brains of presumed shi*jp animals.Copyright © 1991 S. Karger AG, Basel

American Journal of Obstetrics and Gynecology, 2012

A copious watery vaginal discharge was the symptom in 2 similar, although unusual cases. The firs... more A copious watery vaginal discharge was the symptom in 2 similar, although unusual cases. The first patient, a 51-year-old woman, also reported that the discharge was bloody. Twelve years earlier, she had undergone surgery and chemoradiation therapy for cervical cancer. Three years later, she had laser ablation for vaginal intraepithelial neoplasia grade 2. She was then lost to follow-up evaluation until 6 months before her current admission, when she sought treatment for the vaginal exudate. A biopsy identified colonies of Actinomyces species, and she was treated with penicillin. When her symptoms persisted, a second biopsy was performed that revealed squamous cell carcinoma. After a metastatic work-up, she underwent total pelvic exenteration.

American Journal of Obstetrics and Gynecology, 2015

Intrahepatic cholestasis of pregnancy (ICP) is known to be associated with fetal complications. I... more Intrahepatic cholestasis of pregnancy (ICP) is known to be associated with fetal complications. It recently was suggested to be associated possibly with preeclampsia (PET) as well. The objective of this study was to investigate that possibility. The study group included 78 women (54 singleton and 24 twin pregnancies) who had been diagnosed with ICP based on clinical presentation, elevated liver enzymes, and elevated total bile acids (>10 μmol/L). Disease severity was based on total bile acids levels as being severe (>40 μmol/L), moderate (20-40 μmol/L), or mild (10-20 μmol/L). The course of disease was reviewed carefully in each case. The control groups were comprised of apparently healthy women with singleton (n = 200) and twin (n = 100) pregnancies that were drawn randomly from a computerized registry of all the deliveries in our institution during the study period. The total incidence of PET was significantly higher for the patients with ICP who had singleton and twin pregnancies compared with the control groups (singletons: 7.4% vs 1.5%; P < .05; twins: 33.3% vs 6.2%; P < .05, respectively). The incidence of severe PET was also significantly higher in both singleton (11-fold) and twin (8-fold) pregnancies compared with control subjects. Severe ICP, but not mild ICP, was a major risk factor for PET among women with either singleton or twin pregnancies. The timing of the initial presentation of ICP had no effect on PET incidence rates. Preeclampsia occurred usually 2-4 weeks after the diagnosis of ICP, and proteinuria preceded elevated blood pressure in all cases. Moreover, the total bile acid levels among 33 women who were diagnosed as having PET, but not ICP, were within normal range. ICP increases the incidence of PET; severe disease was a major risk factor for preeclampsia. Therefore, we strongly suggest including routine evaluation for preeclampsia in the treatment of women with moderate and severe ICP.

Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 2014

Current Opinion in Otolaryngology & Head and Neck Surgery, 2010

This review discusses the demographics of dizziness in the older person, the evaluation of the ol... more This review discusses the demographics of dizziness in the older person, the evaluation of the older dizzy patient and how the treatment of dizziness in older patients differs from that in younger individuals. Seven percent of all visits to primary care physicians for patients older than 65 years of age are for dizziness, and dizziness is the most common complaint for patients older than 75 years. In a German study, the 12-month prevalence of vertigo in the general population was 5% with an incidence of 1.4% in adults overall. For individuals aged 60-69 the 12-month prevalence was found to be 7.2% and in individuals 70 years of age or older 8.9%. Data from the United States National Health and Nutrition Examination Surveys indicated that the prevalence of vestibular dysfunction for individuals in the seventh decade of life, eighth decade of life, and older was 49.4, 68.7, and 84.8 percent, respectively. Only subtle age effects are seen on caloric and rotational testing whereas vestibular evoked myogenic potentials (VEMPs) change somewhat with age. Particle repositioning for benign paroxysmal positional vertigo combined with vestibular rehabilitation is more effective than only performing the repositioning maneuver. Tai Chi appears to be an effective intervention for older adults at risk for falling. When caring for an older dizzy patient always assess medication use, perform a Dix-Hallpike maneuver, obtain orthostatic vital signs, discuss fall risk precautions, and consider referral for vestibular rehabilitation.

Cancer Research, 2015

Breast tumors are characterized by an extensive desmoplastic stroma, abundantly populated by fibr... more Breast tumors are characterized by an extensive desmoplastic stroma, abundantly populated by fibroblasts. Cancer-associated fibroblasts (CAF) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and invasion. CAF also orchestrate tumor-promoting inflammation in multiple tumor types, including breast cancer. However, the mechanisms through which normal tissue fibroblasts are reprogrammed to tumor-promoting CAFs are mainly obscure. Here, we show that mammary fibroblasts can be educated by breast cancer cells to become activated to a proinflammatory state that supports malignant progression. Proteomic analysis of breast cancer cell-secreted factors identified the secreted proinflammatory mediator osteopontin, which has been implicated in inflammation, tumor progression, and metas-tasis. Osteopontin was highly secreted by mouse and human breast cancer cells, and tumor cell-secreted osteopontin activated a CAF phenotypes in normal mammary fibroblasts in vitro and in vivo. Osteopontin was sufficient to induce fibroblast reprogramming and neutralizing antibodies against osteopontinblocked fibroblast activation induced by tumor cells. The ability of secreted osteopontin to activate mammary fibroblasts relied upon its known receptors CD44 and a V b 3 integrin. Strikingly, osteopontin silencing in tumor cells in vivo attenuated stromal activation and inhibited tumor growth. Our findings establish a critical functional role for paracrine signaling by tumor-derived osteopontin in reprograming normal fibroblasts into tumor-promoting CAFs. Cancer Res; 75(6); 963-73. Ó2015 AACR.

Seminars in Cell & Developmental Biology, 1997

The sensory epithelia of the vertebrate inner ear are comprised of a complex pattern of hair cell... more The sensory epithelia of the vertebrate inner ear are comprised of a complex pattern of hair cells and supporting cells. Several different families of signaling molecules have been shown to play a role in the development and maintenance of this structure. In particular, the steroid/thyroid receptor superfamily, and specifically retinoid and thyroid receptors appear to influence the determination, differentiation, maintenance, and possibly regeneration, of the sensory epithelia of the vertebrate inner ear. Clinical and experimental evidence demonstrates that changes in the relative availability of retinoic acid and thyroid hormone, the ligands for retinoid and thyroid receptors, result in perturbations in the development of hair cell sensory epithelia. Retinoic acid and retinoid receptors appear to play a role in early developmental events including cellular proliferation and determination whereas thyroid hormone and thyroid receptors appear to play a role in later events including differentiation and maintenance.

Psychiatric Genetics, 2010

This study examined the influence of allelic variation in two dopamine genes, the dopamine recept... more This study examined the influence of allelic variation in two dopamine genes, the dopamine receptor D4 (DRD4) gene and the dopamine transporter D1 (DAT1) gene, and paternal attention-deficit hyperactivity disorder (ADHD) symptomatology on the level of ADHD symptoms in 96 four and a half-year-old boys. DNA was collected by means of a buccal swab and genotyped for DRD4 and DAT1. Mothers completed the Dupaul ADHD checklist on their sons. ADHD symptomatology ratings for fathers were based on a summed father self-reported and spouse-reported symptoms (Conners Adult ADHD Rating Scale). There were main effects for DAT1 and father symptomatology for the child Total ADHD and Hyperactivity-Impulsivity scores. The main effects for DRD4 were limited to the child Hyperactivity-Impulsivity scores. Child Inattentive scores were influenced only by father symptomatology. Interaction effects between DAT1 and DRD4 and between DAT1 and the father ADHD risk group were found for child Hyperactivity-Impulsivity scores. Boys with the highest level of symptomatology were those with the 10/10 DAT1 genotype and the DRD4-7 genotype or fathers with high symptomatology. The findings of this study indicate that the risk for ADHD, particularly hyperactivity-impulsivity, is exacerbated in the presence of dopamine risk genes and paternal ADHD symptomatology. This study adds to the growing literature on the efficacy of including multiple genetic and environmental risk factors in studies related to the development of psychopathology.

Otolaryngology -- Head and Neck Surgery, 2013

Objective: 1) To evaluate a novel system for regulating the chitosan-glycero-phosphate (CGP)-base... more Objective: 1) To evaluate a novel system for regulating the chitosan-glycero-phosphate (CGP)-based hydrogel drug delivery to the inner ear. 2) To understand the distribution of gentamicin in the inner ear following CGP drug delivery with and without regulation.